Systemic Inflammation Response Index (SIRI), cancer stem cells and survival of localised gastric adenocarcinoma after curative resection.

Abstract

Systemic Inflammation Response Index (SIRI), based on peripheral neutrophil, monocyte, and lymphocyte counts, was recently developed and used as a marker to predict the survival of patients with malignant tumours. Cancer stem cells (CSCs) can contribute to gastric cancer progression and recurrence. It is not clear whether SIRI is associated with CSCs during gastric cancer development. The SIRI was developed in a training cohort of 455 gastric cancer patients undergoing curative resection between 2007 and 2009, and validated in a validation cohort of 327 patients from 2010 to 2011. CD44+CSCs were measured on tumour sections by immunohistochemical analysis. An optimal cut-off point for the SIRI of 0.82 divided the gastric cancer patients into a low SIRI group (SIRI<0.82) and a high SIRI group (SIRI≥0.82) in the training cohort. Compared with patients who had a SIRI<0.82, patients who had a SIRI≥0.82 had a shorter disease-free survival (DFS) (HR 2.529; 95% CI 1.922-3.326; p<0.001) and shorter disease-special survival (DSS) (HR 2.692; 95% CI 2.022-3.585; p<0.001) in the training cohort, comparable DFS and DSS findings were observed in the validation cohort, even for patients in pathological TNM stage of I subgroup. A SIRI≥0.82 was significantly associated with older age, larger tumour, higher pathological TNM stage, lymphovascular invasion, and perineural invasion. Additionally, patients in the low SIRI group were prone to DFS and DSS benefits from postoperative adjuvant chemotherapy. Univariate and multivariate analyses revealed that SIRI was an independent predictor for DFS and DSS. Furthermore, gastric cancer patients with CD44+CSCs scores had higher SIRI level (mean 1.198 vs. 0.835; p<0.001). In patients with CD44+CSCs, those with SIRI≥0.82 had higher recurrence rates and shorter survival time than patients with SIRI<0. 82. SIRI was a useful prognostic indicator of poor outcomes in patients with gastric cancer and is a promising tool for gastric cancer treatment strategy decisions. The dismal outcomes in patients with high SIRI might be related to CSCs.