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全身炎症反应指数(SIRI)、癌症干细胞与根治性切除术后局部胃腺癌的生存情况

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

作者信息

Li Sen, Lan Xiuwen, Gao Hongyu, Li Zhiguo, Chen Li, Wang Wenpeng, Song Shubin, Wang Yimin, Li Chunfeng, Zhang Hongfeng, Xue Yingwei

机构信息

Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, 150 HaPing Road, Harbin, 150081, China.

Department of Gynecologic Oncology, Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

J Cancer Res Clin Oncol. 2017 Dec;143(12):2455-2468. doi: 10.1007/s00432-017-2506-3. Epub 2017 Aug 21.

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

基于外周血中性粒细胞、单核细胞和淋巴细胞计数的全身炎症反应指数(SIRI)最近被开发出来,并用作预测恶性肿瘤患者生存情况的标志物。癌症干细胞(CSCs)可促进胃癌的进展和复发。目前尚不清楚在胃癌发生过程中SIRI是否与CSCs相关。

方法

在2007年至2009年期间接受根治性切除的455例胃癌患者的训练队列中建立SIRI,并在2010年至2011年的327例患者的验证队列中进行验证。通过免疫组织化学分析在肿瘤切片上检测CD44 + CSCs。

结果

在训练队列中,SIRI的最佳截断点为0.82,将胃癌患者分为低SIRI组(SIRI < 0.82)和高SIRI组(SIRI≥0.82)。与SIRI < 0.82的患者相比,SIRI≥0.82的患者无病生存期(DFS)较短(HR 2.529;95% CI 1.922 - 3.326;p < 0.001),疾病特异性生存期(DSS)较短(HR 2.692;95% CI 2.022 - 3.585;p < 0.001)。在验证队列中观察到了类似的DFS和DSS结果,即使是病理TNM分期为I亚组的患者。SIRI≥0.82与年龄较大、肿瘤较大、病理TNM分期较高、淋巴管浸润和神经周围浸润显著相关。此外,低SIRI组的患者术后辅助化疗更易从DFS和DSS中获益。单因素和多因素分析显示,SIRI是DFS和DSS的独立预测因子。此外,CD44 + CSCs评分的胃癌患者SIRI水平较高(平均值1.198对0.835;p < 0.001)。在CD44 + CSCs患者中,SIRI≥0.82的患者比SIRI < 0.82的患者复发率更高,生存时间更短。

结论

SIRI是胃癌患者不良预后的一个有用的预后指标,是胃癌治疗策略决策的一个有前景的工具。高SIRI患者的不良结局可能与CSCs有关。

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