作者：张竞1,2,3，谢扬1,2,3，王凤1,2,3，齐健1,2,3

单位：1.武汉大学中南医院 消化内科，湖北 武汉 430071；2.肠病湖北省重点实验室，湖北 武汉 430071；3.湖北省肠病医学 临床研究中心，湖北 武汉 430071

Authors:  Zhang Jing1,2,3,  Xie Yang1,2,3,  Wang Feng1,2,3,  Qi Jian1,2,3

Unit:  1.Department of Gastroenterology, Zhongnan Hospital of Wuhan University，Wuhan 430071，Hubei，China；2.Key Laboratory of Intestinal and Colorectal Diseases，Wuhan 430071，Hubei，China；3.Hubei Clinical Research Center of Intestinal and Colorectal Diseases, Wuhan 430071，Hubei，China

摘要：

目的 探讨COL6A3基因与胃癌免疫浸润水平及临床预后的相关性。方法 通过Oncomine、TIMER数据库分析不同癌症中Ⅵ型胶原蛋白α3链(collagen type Ⅵ α3 chain, COL6A3)的表达水平。通过Kaplan-Meier Plotter、GEPIA数据库评估COL6A3对胃癌临床预后的影响。利用TIMER和GEPIA数据库,联合免疫相关细胞的标记基因评估COL6A3在胃癌中与免疫细胞浸润水平的相关性。结果 与正常组织相比,COL6A3在胃癌、结直肠癌和食管癌等组织中的高表达;COL6A3的高表达与胃癌较差的总生存(overall survival, OS)率、后进展生存(post progression survival, PPS)率、首次进展(first progression, FP)率显著相关(OS HR=1.33,P=0.0015; PPS HR=1.54,P<0.001; FP HR=1.36,P=0.003);COL6A3的高表达与Ⅱ～Ⅳ期胃癌患者较差的OS率和PPS率有关,而与Ⅰ期和N0期胃癌患者无关(P=0.23,r=0.18; P=0.09,r=0.16);COL6A3的表达与CD4+T细胞、CD8+T细胞、巨噬细胞、中性粒细胞、树突状细胞在胃癌中的浸润水平呈正相关。结论COL6A3与胃癌免疫浸润水平相关,包括CD8+T细胞、CD4+T细胞、巨噬细胞、中性粒细胞和树突状细胞。COL6A3可作为判断胃癌预后不良的标志物,且与胃癌的免疫浸润呈正相关。

关键词：胃癌; 免疫浸润; 临床预后

Abstract：

Objective To explore the correlation between the COL6A3 gene and immune infiltration level and clinical prognosis of gastric cancer. Methods The mRNA expression levels of collagen type VI α3 chain (COL6A3) in different cancers were analyzed through the Oncomine, Tumor Immune Estimation Resource (TIMER) database. We assessed the effect of COL6A3 on clinical prognosis via Kaplan -Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA). TIMER and GEPIA database were also used to evaluate the correlations between COL6A3 and the infiltrating levels of immune cells in gastric cancer, and relate genes and markers of immune cells in gastric cancer. Results the COL6A3 expression was higher in gastric, colorectal and esophageal tumors compared to the normal tissues. In addition, high COL6A3 expression was significantly correlated with poor overall survival (OS) , post-progression survival (PPS) , first progression (FP) in gastric cancers (OS HR=1.33, P=0.0015; PPS HR=1.54, P<0.001;FP HR=1.36,P=0.003) . Specifically, high COL6A3 expression was correlated with worse OS and PPS in stage Ⅱ to Ⅳ but not stageⅠ and stage N0 gastric cancer patients (P=0.23, r=0.18; P=0.09, r= 0.16) . Moreover, COL6A3 expression was positively correlated with infiltrating levels of CD4+ T and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in and stomach adenocarcinoma (STAD). Conclusions These findings suggest that COL6A3 is correlated with prognosis and immune infiltrating levels including those of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in patients with gastric cancer. COL6A3 can be used as an unfavorable prognostic biomarker for determining prognosis, and positively correlated with immune infiltration in gastric cancer.

Key Words:  Gastric cancer; Immune infiltration; Clinical prognosis