Department of Gastric Cancer, Liaoning Cancer Hospital and Institute (Cancer Hospital of China Medical University), Shenyang 110042, Liaoning Province, China.
Department of Emergency, Sheng Jing Hospital of China Medical University, Shenyang 110042, Liaoning Province, China.
World J Gastroenterol. 2018 Nov 21;24(43):4906-4919. doi: 10.3748/wjg.v24.i43.4906.
To detect significant clusters of co-expressed genes associated with tumorigenesis that might help to predict stomach adenocarcinoma (SA) prognosis.
The Cancer Genome Atlas database was used to obtain RNA sequences as well as complete clinical data of SA and adjacent normal tissues from patients. Weighted gene co-expression network analysis (WGCNA) was used to investigate the meaningful module along with hub genes. Expression of hub genes was analyzed in 362 paraffin-embedded SA biopsy tissues by immunohistochemical staining. Patients were classified into two groups (according to expression of hub genes): Weak expression and over-expression groups. Correlation of biomarkers with clinicopathological factors indicated patient survival.
Whole genome expression level screening identified 6,231 differentially expressed genes. Twenty-four co-expressed gene modules were identified using WGCNA. Pearson's correlation analysis showed that the tan module was the most relevant to tumor stage ( = 0.24, = 7 × 10). In addition, we detected sorting nexin (SNX)10 as the hub gene of the tan module. SNX10 expression was linked to T category ( = 0.042, χ = 8.708), N category ( = 0.000, χ = 18.778), TNM stage ( = 0.001, χ = 16.744) as well as tumor differentiation ( = 0.000, χ = 251.930). Patients with high SNX10 expression tended to have longer disease-free survival (DFS; 44.97 mo 33.85 mo, = 0.000) as well as overall survival (OS; 49.95 40.84 mo, = 0.000) in univariate analysis. Multivariate analysis showed that dismal prognosis could be precisely predicted clinicopathologically using SNX10 [DFS: = 0.014, hazard ratio (HR) = 0.698, 95% confidence interval (CI): 0.524-0.930, OS: = 0.017, HR = 0.704, 95%CI: 0.528-0.940].
This study provides a new technique for screening prognostic biomarkers of SA. Weak expression of SNX10 is linked to poor prognosis, and is a suitable prognostic biomarker of SA.
检测与肿瘤发生相关的显著共表达基因簇，以帮助预测胃腺癌 (SA) 的预后。
利用癌症基因组图谱数据库获取来自患者的 SA 及相邻正常组织的 RNA 序列及完整临床资料。采用加权基因共表达网络分析（WGCNA）分析有意义的模块和枢纽基因。通过免疫组织化学染色分析 362 例石蜡包埋 SA 活检组织中枢纽基因的表达。根据枢纽基因的表达将患者分为两组（弱表达组和过表达组）。分析生物标志物与临床病理因素的相关性以预测患者的生存情况。
全基因组表达水平筛选出 6231 个差异表达基因。WGCNA 鉴定出 24 个共表达基因模块。Pearson 相关分析显示，tan 模块与肿瘤分期相关性最强（ = 0.24， = 7×10）。此外，我们检测到分选连接蛋白（SNX）10 为 tan 模块的枢纽基因。SNX10 的表达与 T 分期（ = 0.042，χ = 8.708）、N 分期（ = 0.000，χ = 18.778）、TNM 分期（ = 0.001，χ = 16.744）和肿瘤分化（ = 0.000，χ = 251.930）相关。SNX10 高表达的患者无病生存期（DFS；44.97 mo 33.85 mo， = 0.000）和总生存期（OS；49.95 40.84 mo， = 0.000）更长，这在单因素分析中得到证实。多因素分析显示，SNX10 可精确预测患者的不良预后[DFS： = 0.014，风险比（HR）= 0.698，95%置信区间（CI）：0.524-0.930，OS： = 0.017，HR = 0.704，95%CI：0.528-0.940]。
本研究为筛选 SA 预后生物标志物提供了一种新方法。SNX10 低表达与预后不良相关，是 SA 的一种合适的预后生物标志物。
