Clinical burden of preoperative albumin-globulin ratio in esophageal cancer patients

Abstract

Background

Lower albumin-globulin ratio (AGR) is associated with increased mortality in several cancers. However, no studies have evaluated the relationship between the AGR and prognostic outcome in esophageal cancer (EC) patients.

Methods

To identify indicators of early recurrence and poor prognosis, we assessed the clinicopathological findings and preoperative laboratory data (carcinoembryonic antigen [CEA], squamous cell carcinoma antigen, total protein, and albumin) of 112 EC patients who underwent surgery. The AGR was calculated as albumin/(total protein–albumin).

Results

A lower AGR was significantly associated with tumor progression. The CEA level was an independent predictor for overall survival (OS) and disease-free survival (DFS). The AGR and CEA combination was identified as a feasible indicator of poor prognosis and early recurrence. Among EC patients without lymph node metastasis, those with lower AGR had poorer DFS and OS than those with higher AGR.

Conclusion

AGR was identified as a significant predictor of OS and DFS in EC patients. Among EC patients without lymph node metastasis, AGR may help identify candidates who might benefit from more intensive adjuvant therapy.

Introduction

Esophageal cancer (EC) is the sixth most common cause of cancer-related death worldwide. In 2012, there were 455,800 estimated cases of EC and 400,200 deaths.1, 2 Recent advances in multimodality therapy, combining systemic chemotherapy with radiotherapy and surgery, could provide survival benefits for EC patients. Nevertheless, the prognosis of EC patients remains poor, and there is a clear need for prognostic biomarkers that can help identify high-risk EC patients who can benefit from intensive neoadjuvant or adjuvant treatment.

Accumulating evidence revealed a close correlation between inflammation and tumorigenesis in various types of cancer.3, 4, 5, 6, 7 Especially in esophageal squamous cell carcinoma, the pathogenesis is deeply related to chronic inflammation caused by alcohol drinking and cigarette smoking. Such chronic inflammation can lead to mucosal injury and subsequent DNA damage.8, 9 Furthermore, inflammatory processes are thought to affect various steps of tumorigenesis and play a pivotal role in the underlying biological mechanisms of resistance to chemotherapeutic treatment for EC patients.10, 11

Albumin and globulin are major serum proteins as well as representative indicators of systemic inflammation. The albumin-globulin ratio (AGR) has been used mainly as a clinical indicator in multiple myeloma and other immunoproliferative disorders. Recently, AGR was identified as a predictor of long-term mortality in patients with nasopharyngeal carcinoma,¹² colorectal cancer,¹³ lung cancer¹⁴ and breast cancer.¹⁵ However, the clinical burden and prognostic impact of the AGR in EC has yet to be elucidated.

Previous works from our group have shown that several inflammatory markers and cytokines, reflecting systemic inflammatory response (IL-1b, IL-1ra, IL-6, IL-10, C-reactive protein (CRP), and albumin) are differentially expressed in the serum of patients with advanced gastrointestinal cancer. Based on those findings, we proposed that these inflammatory markers can be used as predictive biomarkers for postoperative nutrition status, morbidity, and mortality in patients with gastrointestinal cancer.16, 17, 18, 19, 20, 21, 22, 23, 24 In this study, we systematically investigated preoperative serum levels of albumin, globulin, and other representative tumor markers using clinical information from a large cohort of patients with EC to clarify their clinical significance as predictors of prognosis and recurrence in EC patients.