Skip to main content

Main menu

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Editorial Policies
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Other Publications
    • In Vivo
    • Anticancer Research
    • Cancer Genomics & Proteomics

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
In Vivo
  • Other Publications
    • In Vivo
    • Anticancer Research
    • Cancer Genomics & Proteomics
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
In Vivo

Advanced Search

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Editorial Policies
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Visit iiar on Facebook
  • Follow us on Linkedin
Research ArticleExperimental Studies

High MCM6 Expression as a Potential Prognostic Marker in Clear-cell Renal Cell Carcinoma

NU-RI JANG, JINA BAEK, YOUNGHWII KO, PHIL HYUN SONG and MI-JIN GU
In Vivo January 2021, 35 (1) 299-306; DOI: https://doi.org/10.21873/invivo.12259
NU-RI JANG
1Department of Pathology, Yeungnam University College of Medicine, Gyeongsan, Republic of Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
JINA BAEK
1Department of Pathology, Yeungnam University College of Medicine, Gyeongsan, Republic of Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
YOUNGHWII KO
2Department of Urology, Yeungnam University College of Medicine, Gyeongsan, Republic of Korea
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
PHIL HYUN SONG
2Department of Urology, Yeungnam University College of Medicine, Gyeongsan, Republic of Korea
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MI-JIN GU
1Department of Pathology, Yeungnam University College of Medicine, Gyeongsan, Republic of Korea;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: mjgu@yu.ac.kr
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Aim: Minichromosome maintenance (MCM) proteins are involved in initiation of DNA replication and cell-cycle progression. Loss of MCM function results in genomic instability and causes carcinogenesis. Among MCM genes, the role and prognostic value of MCM6 expression in clear-cell renal cell carcinoma (ccRCC) has not been elucidated. Materials and Methods: We assessed the mRNA expression level of MCM6 using the Gene Expression Profiling Interactive Analysis database and investigated MCM6 protein expression by immunohistochemistry in 238 ccRCC cases. Results: High MCM6 expression was significantly associated with increasing tumor size, pT, stage, tumor necrosis, and metastasis. Furthermore, high MCM6 expression was significantly associated with shorter overall and disease-free survival, and was an independent unfavorable prognostic marker. Regarding patients with metastasis, high MCM6-expressing ccRCC conferred significantly shorter survival than for those with low expression. Conclusion: A high MCM6 expression level may be a promising biomarker to predict tumor progression, metastasis, and survival in patients with ccRCC.

  • MCM6
  • clear cell renal cell carcinoma
  • prognosis
  • biomarker

Clear-cell renal cell carcinoma (ccRCC) is the most common type of RCC, accounting for 70-80% of all RCC cases (1, 2). Patients with ccRCC generally have worse outcomes compared to those with other RCC types (3). At diagnosis, one-third of patients with ccRCC already exhibit metastasis (4). Surgical resection is the most effective treatment for localized ccRCC, and its overall 5-year survival rate is up to 97.4% for stage I ccRCC and 89.9% for stage II (5). However, 30-35% of patients who undergo nephrectomy experience relapse and metastasis. Metastatic and inoperable ccRCC is refractory to conventional chemotherapy and radiotherapy and has a 5-year survival rate of approximately 20% (6, 7). Therefore, the identification of potential biomarkers to predict disease progression and prognosis remains crucial.

The minichromosome maintenance (MCM) protein complex consists of six highly-conserved proteins (MCM2-7) and plays an essential role in the initiation of DNA replication (8). MCM proteins are expressed only during the cell cycle and are down-regulated and dissociated from chromatin in quiescent cells. Thus, they are considered useful proliferation markers (9, 10). In addition, the elevation or depletion of MCM levels causes genomic instability and leads to carcinogenesis (11). MCM6 expression has been evaluated in various human cancer types, including breast cancer, hepatocellular carcinoma, endometrial adenocarcinoma, craniopharyngioma, meningioma, chondrosarcoma, pancreatic adenocarcinoma, and colorectal cancer (8, 12-15). In those studies, MCM6 was found to be overexpressed in cancer tissue and was associated with important clinicopathologicaI factors. However, to the best of our knowledge, this is the first study to evaluate MCM6 protein expression and its prognostic significance in ccRCC.

The aim of this study was to assess the MCM6 expression level in ccRCC, evaluate its clinicopathological significance, and determine whether MCM6 can be used as a potential prognostic and predictive marker of ccRCC.

Materials and Methods

Public database analysis. We assessed the Gene Expression Profiling Interactive Analysis (GEPIA; http;//gepia.cancer-pku.cn) database to evaluate the RNA-Seq mRNA expression of MCM6 in 523 ccRCC samples and 100 normal samples from the Cancer Genome Atlas and Genotype-Tissue Expression (GTEx) projects.

Patient data and histological review. We included 238 cases of ccRCC who underwent nephrectomy between May 2000 and July 2017 at Yeungnam University Medical Center. This study was approved by the Ethics Committee of the Yeungnam University College of Medicine (2020-06-009). Written informed consent was exempted by the Ethics Committee due to the retrospective nature of the study. Clinical, pathological, and follow-up data were obtained from the patients’ medical records. Cases that involved pre-operative therapy, insufficient clinicopathological data, or tissue unavailability for immunohistochemical staining were excluded from the analysis. The clinicopathological data included data regarding patient sex, age, tumor size, tumor necrosis, tumor hemorrhage, lymphovascular invasion (LVI), TNM (tumor, node, metastasis) stage, metastasis/recurrence, and nuclear grade (based on the 2016 World Health Organization classification of Tumors of the Urinary System and Male Genital Organs (2). Tumor grading and staging were performed according to the eighth American Joint Committee on Cancer TNM Staging System (16). Overall survival (OS) was defined as the period from the date of diagnosis to the date of death. Disease-free survival (DFS) was evaluated as the period from the date of diagnosis to the date of first recurrence, distant metastasis, or last follow-up date. The OS and DFS data were obtained from the medical charts or the microdata integrated service of South Korea.

Tissue microarray construction. Tissue microarrays (TMAs) were constructed using paraffin-embedded blocks of ccRCC tissues. Two to four 1.5-mm tissue cores that represented the tumor areas of patients were included in the TMA. Non-neoplastic kidney, lymph node, gastric mucosa, breast cancer, and normal liver parenchyma tissues were included as a control in each TMA section. One section from each TMA was stained with hematoxylin and eosin and assessed to confirm the histological presence of representative ccRCC features.

Immunohistochemical analyses and scoring. The 4-μm-thick tissue sections were deparaffinized and rehydrated. Immunohistochemistry for MCM6 was performed using an automated Benchmark platform (Ventana Medical Systems, Tucson, AZ, USA). Antigen retrieval was carried out using the Cell Conditioning Solution (mild cc1; Ventana Medical Systems), and the samples were then incubated with MCM6 antibody (ERP17686, rabbit monoclonal, 1:1,000; Abcam, Cambridge, UK) for 40 min at room temperature. Stains were visualized using an UltraView universal DAB detection kit (Ventana Medical System). Negative controls were performed in the absence of primary antibody. The slides were then scanned using a Leica Aperio ScanScope (Leica Biosystems, Vista, CA, USA) system at 40× magnification, and the images were captured using a Leica ImageScope.

MCM6 expression was defined as positive when the tumor cells had moderate or strong nuclear immunoreactivity. Manual counting of MCM6-expressing cells was performed on a computer monitor using the scanned images. We selected two to four hotspots (with a minimum of 500 tumor cells) for each case, and all tumor nuclei and MCM6-positive tumor cells were counted by clicking on the images to yield a continuous score from 0 to 100.

Statistical analysis. To identify the optimal cutoff value that would demonstrate the highest accuracy in predicting outcomes, receiver operating characteristic curve analysis was used. Quantitative variables were compared using Student’s t-test. Categorical variables were compared using Fisher’s exact test. OS and DFS curves were assessed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analyses were performed using pathological variables that were recognized as significant in the univariate survival analyses. Additionally, hazard ratios (HRs) and relevant 95% confidence intervals (CIs) were assessed. All statistical analyses were conducted using SPSS software version 25.0 (IBM, Armonk, NY, USA). A p-value of less than 0.05 was considered statistically significant.

Results

mRNA expression of MCM6 gene. In the GEPIA data, the MCM6 gene was found to be up-regulated in the ccRCC samples when compared to normal kidney samples (Figure 1). The MCM6 gene expression level did not differ significantly between stages; however, it was found to be a slightly more up-regulated in stage IV ccRCC samples when compared to other stages (Figure 2). Patients with RCCs with high MCM6 gene expression tended to have better OS and shorter DFS than those with lower expression (p=0.35 and p=0.22) (Figure 3).

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Distribution of minichromosome maintenance 6 (MCM6) gene expression in clear-cell renal carcinoma tissue and normal tissue. MCM6 gene was significantly up-regulated (p<0.01) in clear-cell renal cell carcinoma [mean value of log2(TPM+1)]. TPM: Transcripts per million.

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Distribution of minichromosome maintenance 6 (MCM6) gene expression in different stages of clear-cell renal cell carcinoma.

Figure 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 3.

In the Gene Expression Profiling Interactive Analysis data, high minichromosome maintenance 6 (MCM6) gene expression tended to confer better overall (A) (p=0.35) and worse disease-free (B) (p=0.22) survival than low expression.

Patient cohort and clinical characteristics. The patient cohort included in this study consisted of 238 patients (173 males and 65 females). The mean age was 57.6 years (range=26-93 years), and the tumor size ranged from 9 to 14.5 cm (mean=4.4 cm). The mean follow-up time was 93.9 months (range=1-217 months). During the follow-up period, 20 patients (8.4%) experienced tumor recurrence or metastasis and 26 patients (10.9%) died.

Immunohistochemical analysis of MCM6 expression. MCM6 was found to be rarely expressed in non-neoplastic renal tubular epithelium (<1%), and immunoreactivity was not observed in the glomerulus (Figure 4A). Notably, the MCM6 expression level in ccRCC samples (Figure 4B) ranged from 0% to 83% (mean=9.8%). The cutoff value for MCM6-positivity with the highest accuracy was 20%. The global predictive accuracy (area under the receiver operating characteristics curve) was found to be 0.709% (95% confidence intervaI=0.588-0.830; p<0.0001). We therefore defined samples with high MCM6 expression as samples in which more than 20% of the tumor cells exhibited nuclear staining. Overall, 47 out of 238 (19.7%) ccRCC samples showed high MCM6 expression (Figure 4C).

Figure 4.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 4.

Immunohistochemical analysis of minichromosome maintenance 6 (MCM6) expression. A: MCM6 expression was found only rarely in tubule, not in glomeruli in normal kidney (×20). B: Low MCM6 expression (×10). C: High MCM6 expression (×10).

MCM6 expression is correlated with advanced clinico - pathological factors. High MCM6 expression was significantly correlated with increasing tumor size (p=0.025) and nuclear grade (p=0.001), and with tumor necrosis (p=0.006). MCM6 was found to be significantly overexpressed in patients with pT2 and pT3 when compared to those with pT1 (p=0.016). In addition, a high MCM6 expression level was associated with metastasis (p=0.001) and increasing stage (p=0.004). Patients with LVI also tended to have higher MCM6 expression but the differences were not statistically significant (p=0.058). No significant association was observed between high MCM6 expression and sex, tumor hemorrhage, or lymph node metastasis. The results are detailed in Table I.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table I.

Relationships between minichromosome maintenance 6 (MCM6) expression and clinicopathological factors.

MCM6 expression is associated with poor outcome. The Kaplan-Meier curve showed that patients with high MCM6 expression had a significantly worse OS and DFS (both p<0.0001) compared to those with low MCM6 expression (Figures 5 and 6). In univariate analyses, OS and DFS were found to be shorter in patients with ccRCC with LVI, tumor necrosis, metastasis, and high MCM6 expression (all p<0.0001). Moreover, survival was found to worsen as pT stage increased. Patients with stage III or IV ccRCC were revealed to have a similar survival time of only a few months, which was significantly shorter compared to that of patients with stage I or II ccRCC. In multivariate analyses, high MCM6 expression and stage III and IV ccRCC were independent predictors of poorer OS and DFS. Additionally, the presence of metastases was found to be an independent prognostic factor for poorer DFS. The data are summarized in Table II and III.

Figure 5.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 5.

Survival curves for the whole patient cohort according to minichromosome maintenance 6 (MCM6) protein expression. A: Cumulative overall survival. B: Disease-free survival. High MCM6 expression was significantly associated with worse survival.

Figure 6.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 6.

Survival curves according to minichromosome maintenance 6 (MCM6) protein expression in patients with metastasis of clear-cell renal cell carcinoma. Those with high MCM6 expression had significantly worse overall (A) and disease-free (B) survival.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table II.

Univariate and multivariate analyses of the associations between clinicopathological factors and overall survival.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table III.

Univariate and multivariate analyses of the associations between clinicopathological factors and overall survival.

Discussion

DNA replication is a key process in cell proliferation and growth (17). MCM proteins are key regulators of DNA replication, and dysregulation of MCM proteins may cause developmental defects or cancer (13). The up-regulation of MCM genes has been observed in many human cancer types and was associated with histological grade, TNM stage, or survival (9). However, some controversial results have been reported in colorectal cancer and lung adenocarcinoma (18). Gou et al. reported in a meta-analysis that MCM2, MCM5, and MCM7 were associated with worse outcomes in human cancer (18). In addition, several studies have also assessed the clinicopathological significance of MCM protein expression, and its role as a proliferation marker in comparison to Ki-67. Notably, the majority of those studies were mainly conducted on MCM2 protein expression among the MCM family members. The results of those studies showed that high MCM2 expression was a marker of poor prognosis and MCM2 was proven to be a more reliable and useful proliferation marker than Ki-67 in many types of human cancer (8, 9, 19-21). The prognostic value of Ki-67 in RCC is controversial and inconsistent. Some studies have reported that a high Ki-67 index is correlated with an unfavorable prognosis in RCC (22-24). In contrast, other studies found that the Ki-67 index was not associated with prognosis (25, 26). The aforementioned studies used different cutoff values for positive Ki-67 expression, ranging between 5 and 50%. Additionally, tumor proliferation markers, including Ki-67, are not routinely used to predict prognosis in RCC.

High MCM6 expression was associated with poor survival and higher histological grade in endometrioid endometrial adenocarcinoma and low-grade chondrosarcoma (15, 27). Patients with high MCM6 expression level in non-small cell lung cancer, mantle cell lymphoma, and craniopharyngioma were also found to have worse survival and an increased risk of death (15, 28, 29). In breast cancer, high MCM6 expression was also associated with a higher histological grade (14). Notably, in hepatocellular carcinoma, MCM6 was found to be the best diagnostic and prognostic marker when compared to the other MCM proteins (30).

There have been a few studies that have investigated the expression of MCM proteins in RCC but the majority of those studies were on the MCM2 expression in RCC. In addition, they included all histological types of RCC – ccRCC, papillary RCC, chromophobe RCC, transitional cell carcinoma, and even oncocytoma (21, 31-33). These studies suggested that MCM2 is a useful proliferation marker, and its expression is associated with nuclear grade (21, 31, 33). In a study using gene-expression data, the overexpression of MCM genes was found to be an independent prognostic factor of RCC (34). That study was also conducted on all histological types of RCC. High MCM5 expression in RCC was associated with lymph node metastasis, distant metastasis, clinical stage, and a shorter OS (32).

In the present study, high MCM6 expression in ccRCC was found to be correlated with aggressive clinicopathological factors and especially associated with tumor progression (as reflected by increasing tumor size, pT stage, stage, and metastasis). Similar to the GEPIA results, the frequency of high MCM6 expression was not significantly different between stage I, II, and III ccRCC, but was a little up-regulated in stage IV ccRCC. This suggests that high MCM6 expression may be associated with metastasis rather than disease stage, as there was no pT4 case included in the present study. Furthermore, in ccRCC with metastasis, patients with high MCM6 expression had a significantly shorter OS (mean=48.1 months) and DFS (mean=13.7 months) than those with low MCM6 expression (mean of 74.5 months and 52.2 months) (Figure 6). This might support our hypothesis that MCM6 plays an oncogenic role in tumor proliferation and progression, and suggests that it might be a promising potential prognostic marker for ccRCC. The MCM6 labeling index with a cutoff value of 20% was found to be a highly significant predictor of aggressive clinicopathological factors, metastasis, and poor survival. However, further studies with a larger number of ccRCC cases are required to validate the cutoff value.

In conclusion, our study is the first to assess MCM6 expression and its prognostic value in ccRCC. As such, we revealed that high MCM6 expression was significantly associated with aggressive clinicopathological factors and was an independent adverse prognostic factor. Thus, the assessment of MCM6 expression in patients with ccRCC as a routine pathological practice might provide useful information in regard to aggressive behavior. Additionally, MCM6 expression might be a useful predictive marker of metastasis and poor survival. However, future studies are needed to verify the cutoff value of MCM6 expression and to investigate whether MCM6 can serve as a potential therapeutic target.

Acknowledgements

This work was supported by a grant from the Chunma Medical Research Foundation, Korea, 2020.

Footnotes

  • Authors’ Contributions

    MJG carried out experiments, analyzed data, and prepared the article. NRJ and JAB reviewed pathological data, carried out experiments and analyzed data. YWK and PHS prepared clinical data.

  • This article is freely accessible online.

  • Conflicts of Interest

    The Authors declare that they have no conflicts of interest.

  • Received September 17, 2020.
  • Revision received October 3, 2020.
  • Accepted October 7, 2020.
  • Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved

References

  1. ↵
    1. Rini BI,
    2. Campbell SC and
    3. Escudier B
    : Renal cell carcinoma. Lancet 373(9669): 1119-1132, 2009. PMID: 26935559. DOI: 10.1016/j.eururo.2016.02.029
    OpenUrlCrossRefPubMed
  2. ↵
    1. Moch H,
    2. Cubilla AL,
    3. Humphrey PA,
    4. Reuter VE and
    5. Ulbright TM
    : The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol 70(1): 93-105, 2016. PMID: 26935559. DOI: 10.1016/j.eururo.2016.02.029
    OpenUrlCrossRefPubMed
  3. ↵
    1. Lopez-Beltran A,
    2. Carrasco JC,
    3. Cheng L,
    4. Scarpelli M,
    5. Kirkali Z and
    6. Montironi R
    : 2009 Update on the classification of renal epithelial tumors in adults. Int J Urol 16(5): 432-443, 2009. PMID: 19453547. DOI: 10.1111/j.1442-2042.2009.02302.x
    OpenUrlCrossRefPubMed
  4. ↵
    1. Dagher J,
    2. Kammerer-Jacquet SF,
    3. Dugay F,
    4. Beaumont M,
    5. Lespagnol A,
    6. Cornevin L,
    7. Verhoest G,
    8. Bensalah K,
    9. Rioux-Leclercq N and
    10. Belaud-Rotureau MA
    : Clear-cell renal cell carcinoma: A comparative study of histological and chromosomal characteristics between primary tumors and their corresponding metastases. Virchows Arch 471(1): 107-115, 2017. PMID: 28488172. DOI: 10.1007/s00428-017-2124-0
    OpenUrlCrossRef
  5. ↵
    1. Cheaib JG,
    2. Patel HD,
    3. Johnson MH,
    4. Gorin MA,
    5. Haut ER,
    6. Canner JK,
    7. Allaf ME and
    8. Pierorazio PM
    : Stage-specific conditional survival in renal cell carcinoma after nephrectomy. Urol Oncol 38(1): 6 e1-6 e7, 2020. PMID: 31522864. DOI: 10.1016/j.urolonc.2019.08.011
    OpenUrlCrossRef
  6. ↵
    1. Shinmei S,
    2. Goto K,
    3. Sentani K,
    4. Anami K,
    5. Hayashi T,
    6. Teishima J,
    7. Matsubara A,
    8. Oue N,
    9. Kitadai Y,
    10. Yasui W and
    11. Yasui W
    : MicroRNA-155 is a predictive marker for survival in patients with clearcell renal cell carcinoma. Int J Urol 20(5): 468-477, 2013. PMID: 23050614. DOI: 10.1111/j.1442-2042.2012.03182.x
    OpenUrlCrossRefPubMed
  7. ↵
    1. Ficarra V,
    2. Guillè F,
    3. Schips L,
    4. de la Taille A,
    5. Prayer Galetti T,
    6. Tostain J,
    7. Cindolo L,
    8. Novara G,
    9. Zigeuner R,
    10. Bratti E,
    11. Li G,
    12. Altieri V,
    13. Abbou CC,
    14. Zanolla L,
    15. Artibani W, and
    16. Patard J-J
    : Proposal for revision of the TNM classification system for renal cell carcinoma. Cancer 104(10): 2116-2123, 2005. PMID: 16208703. DOI: 10.1002/cncr.21465
    OpenUrlCrossRefPubMed
  8. ↵
    1. Gauchotte G,
    2. Vigouroux C,
    3. Rech F,
    4. Battaglia-Hsu SF,
    5. Soudant M,
    6. PineIli C,
    7. Civit T,
    8. Taillandier L,
    9. Vignaud JM and
    10. Bressenot A
    : Expression of mini-chromosome maintenance MCM6 protein in meningiomas is strongly correlated with histological grade and clinical outcome. Am J Surg Pathol 36(2): 283-291, 2012. PMID: 22020044. DOI: 10.1097/PAS.0b013e318235ee03
    OpenUrlCrossRefPubMed
  9. ↵
    1. Giaginis C,
    2. Vgenopoulou S,
    3. Vielh P and
    4. Theocharis S
    : Mcm proteins as diagnostic and prognostic tumor markers in the clinical setting. Histol Histopathol 25(3): 351-370, 2010. PMID: 20054807. DOI: 10.14670/HH-25.351
    OpenUrlCrossRefPubMed
  10. ↵
    1. Bailis JM and
    2. Forsburg SL
    : MCM proteins: DNA damage, mutagenesis and repair. Curr Opin Genet Dev 14(1): 17-21, 2004. PMID: 15108800. DOI: 10.1016/j.gde.2003.11.002
    OpenUrlCrossRefPubMed
  11. ↵
    1. Das M,
    2. Singh S,
    3. Pradhan S and
    4. Narayan G
    : MCM PARadox: Abundance of eukaryotic replicative helicases and genomic integrity. Mol Biol Int 2014: 574850, 2014. PMID: 25386362. DOI: 10.1155/2014/574850
    OpenUrlCrossRefPubMed
  12. ↵
    1. Hendricks AA-O,
    2. Gieseler F,
    3. Nazzal S,
    4. Bräsen JH,
    5. Lucius R,
    6. Sipos B,
    7. Claasen JH,
    8. Becker T,
    9. Hinz S,
    10. Burmeister G,
    11. Schafmayer C and
    12. Schrader C
    : Prognostic relevance of topoisomerase IIα and minichromosome maintenance protein 6 expression in colorectal cancer. BMC Cancer 19(1): 429, 2019. PMID: 31072339. DOI: 10.1186/s12885-019-5631-3
    OpenUrlCrossRef
  13. ↵
    1. Liao X,
    2. Han C,
    3. Wang X,
    4. Huang K,
    5. Yu T,
    6. Yang C,
    7. Huang R,
    8. Liu Z,
    9. Han Q and
    10. Peng T
    : Prognostic value of minichromosome maintenance mrna expression in early-stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy. Cancer Manage Res 10: 3255-3271, 2018. DOI: 10.2147/CMAR.S171293
    OpenUrlCrossRef
  14. ↵
    1. Issac MSM,
    2. Yousef E,
    3. Tahir MR and
    4. Gaboury LA
    : MCM2, MCM4, and MCM6 in breast cancer: Clinical utility in diagnosis and prognosis. Neoplasia 21(10): 1015-1035, 2019. PMID: 31476594. DOI: 10.1016/j.neo.2019.07.011
    OpenUrlCrossRef
  15. ↵
    1. Hotton J,
    2. Agopiantz M,
    3. Leroux A,
    4. Charra-Brunaud C,
    5. Marie B,
    6. Busby-Venner H,
    7. Morel O,
    8. Gueant JL,
    9. Vignaud JM,
    10. Battaglia-Hsu SF and
    11. Gauchotte G
    : Minichromosome maintenance complex component 6 (MCM6) expression correlates with histological grade and survival in endometrioid endometrial adenocarcinoma. Virchows Arch 472(4): 623-633, 2018. PMID: 29243125. DOI: 10.1007/s00428-017-2278-9
    OpenUrlCrossRef
  16. ↵
    1. Amin MB and
    2. Edge SB
    : AJCC Cancer Staging Manual. Springer, 2017.
  17. ↵
    1. Kaur G,
    2. Balasubramaniam SD,
    3. Lee YJ,
    4. Balakrishnan V and
    5. Oon CE
    : Minichromosome maintenance complex (MCM) genes profiling and MCM2 protein expression in cervical cancer development. Asian Pac J Cancer Prev 20(10): 3043-3049, 2019. PMID: 31653153. DOI: 10.31557/APJCP.2019.20.10.3043
    OpenUrlCrossRef
  18. ↵
    1. Gou K,
    2. Liu J,
    3. Feng X,
    4. Li H,
    5. Yuan Y and
    6. Xing C
    : Expression of minichromosome maintenance proteins (MCM) and cancer prognosis: A meta-analysis. J Cancer 9(8): 1518-1526, 2018. PMID: 29721062. DOI: 10.7150/jca.22691
    OpenUrlCrossRef
  19. ↵
    1. Shetty A,
    2. Loddo M,
    3. Fanshawe T,
    4. Prevost AT,
    5. Sainsbury R,
    6. Williams GH and
    7. Stoeber K
    : DNA replication licensing and cell cycle kinetics of normal and neoplastic breast. Br J Cancer 93(11): 1295-1300, 2005. PMID: 16278669. DOI: 10.1038/sj.bjc.6602829
    OpenUrlCrossRefPubMed
    1. Huang HY,
    2. Huang WW,
    3. Lin CN,
    4. Eng HL,
    5. Li SH,
    6. Li CF,
    7. Lu D,
    8. Yu SC and
    9. Hsiung CY
    : Immunohistochemical expression of p16 INK4A, KI-67, and MCM2 proteins in gastrointestinal stromal tumors: Prognostic implications and correlations with risk stratification of nih consensus criteria. Ann Surg Oncol 13(12): 1633-1644, 2006. PMID: 17013685. DOI: 10.1245/s10434-006-9188-4
    OpenUrlCrossRefPubMed
  20. ↵
    1. Rodins K,
    2. Cheale M,
    3. Coleman N and
    4. Fox SB
    : Minichromosome maintenance protein 2 expression in normal kidney and renal cell carcinomas: Relationship to tumor dormancy and potential clinical utility. Clin Cancer Res 8(4): 1075-1081, 2002. PMID: 11948116.
    OpenUrlAbstract/FREE Full Text
  21. ↵
    1. Virman JP,
    2. Bono P,
    3. Luukkaala TH,
    4. Sunela KL,
    5. Kujala PM and
    6. Kellokumpu-Lehtinen PL
    : Combined angiogenesis and proliferation markers’ expressions as long-term prognostic factors in renal cell cancer. Clin Genitourin Cancer 14(4): e283-289, 2016. PMID: 26821530. DOI: 10.1016/j.clgc.2015.12.014
    OpenUrlCrossRef
    1. Weber T,
    2. Meinhardt M,
    3. Zastrow S,
    4. Wienke A,
    5. Fuessel S and
    6. Wirth MP
    : Immunohistochemical analysis of prognostic protein markers for primary localized clear cell renal cell carcinoma. Cancer Invest 31(1): 51-59, 2013. PMID: 23327192. DOI: 10.3109/07357907.2012.749267
    OpenUrlCrossRefPubMed
  22. ↵
    1. Teng J,
    2. Gao Y,
    3. Chen M,
    4. Wang K,
    5. Cui X,
    6. Liu Y and
    7. Xu D
    : Prognostic value of clinical and pathological factors for surgically treated localized clear cell renal cell carcinoma. Chin Med J 127(9): 1640-1644, 2014. PMID: 24791867.
    OpenUrl
  23. ↵
    1. Zheng K,
    2. Zhu W,
    3. Tan J,
    4. Wu W,
    5. Yang S and
    6. Zhang J
    : Retrospective analysis of a large patient sample to determine p53 and Ki67 expressions in renal cell carcinoma. J BUON 19(2): 512-516, 2014. PMID: 24965414.
    OpenUrl
  24. ↵
    1. Gontero P,
    2. Ceratti G,
    3. Guglielmetti S,
    4. Andorno A,
    5. Terrone C,
    6. Bonvini D,
    7. Faggiano F,
    8. Tizzani A,
    9. Frea B and
    10. Valente G
    : Prognostic factors in a prospective series of papillary renal cell carcinoma. BJU Int 102(6): 697-702, 2008. PMID: 18489525. DOI: 10.1111/j.1464-410X.2008.07756.x
    OpenUrlCrossRefPubMed
  25. ↵
    1. Helfenstein A,
    2. Frahm SO,
    3. Krams M,
    4. Drescher W,
    5. Parwaresch R and
    6. Hassenpflug J
    : Minichromosome maintenance protein (MCM6) in low-grade chondrosarcoma: Distinction from enchondroma and identification of progressive tumors. Am J Clin Pathol 122(6): 912-918, 2004. PMID: 15539383. DOI: 10.1309/G638-TKNN-G2CJ-UXWL
    OpenUrlCrossRefPubMed
  26. ↵
    1. Vigouroux C,
    2. Casse JM,
    3. Battaglia-Hsu SF,
    4. Brochin L,
    5. Luc A,
    6. Paris C,
    7. Lacomme S,
    8. Gueant JL,
    9. Vignaud JM and
    10. Gauchotte G
    : Methyl(r217)HUR and MCM6 are inversely correlated and are prognostic markers in non small cell lung carcinoma. Lung Cancer 89(2): 189-196, 2015. PMID: 26013954. DOI: 10.1016/j.lungcan.2015.05.008
    OpenUrlCrossRef
  27. ↵
    1. Xu J,
    2. Zhang S,
    3. You C,
    4. Huang S,
    5. Cai B and
    6. Wang X
    : Expression of human MCM6 and DNA TOPO II alpha in craniopharyngiomas and its correlation with recurrence of the tumor. J Neurooncol 83(2): 183-189, 2007. PMID: 17410335. DOI: 10.1007/s11060-006-9284-0
    OpenUrlCrossRefPubMed
  28. ↵
    1. Liu M,
    2. Hu Q,
    3. Tu M,
    4. Wang X,
    5. Yang Z,
    6. Yang G and
    7. Luo R
    : MCM6 promotes metastasis of hepatocellular carcinoma via MEK/ERK pathway and serves as a novel serum biomarker for early recurrence. J Exp Clin Cancer Res 37(1): 10, 2018. PMID: 29357919. DOI: 10.1186/s13046-017-0669-z
    OpenUrlCrossRef
  29. ↵
    1. Dudderidge TJ,
    2. Stoeber K,
    3. Loddo M,
    4. Atkinson G,
    5. Fanshawe T,
    6. Griffiths DF and
    7. Williams GH
    : MCM2, geminin, and Ki67 define proliferative state and are prognostic markers in renal cell carcinoma. Clin Cancer Res 11(7): 2510-2517, 2005. PMID: 15814627. DOI: 10.1158/1078-0432.CCR-04-1776
    OpenUrlAbstract/FREE Full Text
  30. ↵
    1. Gong B,
    2. Ma M,
    3. Yang X,
    4. Xie W,
    5. Luo Y and
    6. Sun T
    : MCM5 promotes tumour proliferation and correlates with the progression and prognosis of renal cell carcinoma. Int Urol Nephrol 51(9): 1517-1526, 2019. PMID: 31190295. DOI: 10.1007/s11255-019-02169-3
    OpenUrlCrossRef
  31. ↵
    1. Mehdi MZ,
    2. Nagi AH and
    3. Naseem N
    : MCM-2 and Ki-67 as proliferation markers in renal cell carcinoma: A quantitative and semi - quantitative analysis. Int Braz J Urol 42(6): 1121-1128, 2016. PMID: 27532114. DOI: 10.1590/S1677-5538.IBJU.2015.0388
    OpenUrlCrossRef
  32. ↵
    1. Zhong H,
    2. Chen B,
    3. Neves H,
    4. Xing J,
    5. Ye Y,
    6. Lin Y,
    7. Zhuang G,
    8. Zhang SD,
    9. Huang J and
    10. Kwok HF
    : Expression of minichromosome maintenance genes in renal cell carcinoma. Cancer Manag Res 9: 637-647, 2017. PMID: 29180899. DOI: 10.2147/CMAR.S146528
    OpenUrlCrossRef
PreviousNext
Back to top

In this issue

In Vivo
Vol. 35, Issue 1
January-February 2021
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Ed Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on In Vivo.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
High MCM6 Expression as a Potential Prognostic Marker in Clear-cell Renal Cell Carcinoma
(Your Name) has sent you a message from In Vivo
(Your Name) thought you would like to see the In Vivo web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
1 + 1 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
High MCM6 Expression as a Potential Prognostic Marker in Clear-cell Renal Cell Carcinoma
NU-RI JANG, JINA BAEK, YOUNGHWII KO, PHIL HYUN SONG, MI-JIN GU
In Vivo Jan 2021, 35 (1) 299-306; DOI: 10.21873/invivo.12259

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
High MCM6 Expression as a Potential Prognostic Marker in Clear-cell Renal Cell Carcinoma
NU-RI JANG, JINA BAEK, YOUNGHWII KO, PHIL HYUN SONG, MI-JIN GU
In Vivo Jan 2021, 35 (1) 299-306; DOI: 10.21873/invivo.12259
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgements
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • Prognostic Evaluation of the Site of Invasion in Pathological Stage T3a Renal Cell Carcinoma
  • Google Scholar

More in this TOC Section

  • Evaluation of the Relationship Between miRNA-22-3p and Gal-9 Levels in Glioblastoma
  • Metformin Inhibits the Estrogen-mediated Epithelial-Mesenchymal Transition of Ectopic Endometrial Stromal Cells in Endometriosis
  • MCC950 Ameliorates Acute Exogenous Lipoid Pneumonia Induced by Sewing Machine Oil in Rats via the NF-κB/NLRP3 Inflammasome Pathway
Show more Experimental Studies

Similar Articles

Keywords

  • MCM6
  • Clear cell renal cell carcinoma
  • prognosis
  • biomarker
In Vivo

© 2023 In Vivo

Powered by HighWire