Zheng Kaitian, Wang Ye, Wang Jiancheng, Wang Congjun, Chen Junqiang
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Front Surg. 2022 Sep 30;9:964203. doi: 10.3389/fsurg.2022.964203. eCollection 2022.
(HP) infection is one of the leading causes of gastric cancer (GC). However, the interaction between HP and the TME, and its carcinogenic mechanism remains unknown.
The HP-related prognostic genes were identified based on HP infection-related gene markers and HP infection sample datasets by risk method and NMF algorithm. Principal component analysis (PCA) algorithm was used to constructed the HPscore system. The "limma" R package was employed to determine differentially expressed genes. In addition, the R packages, such as "xCell" and "GSVA", was used to analyze the relationship between the HPscore and tumor microenvironment. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to verify the expression levels of 28 HP-related prognostic genes in tissues.
We successfully identified 28 HP-related prognostic genes that accurately classified the GC population. There are significant differences in survival between different subgroups (high-, low-risk and cluster_1,2). Thereafter, the HPscore system was constructed to evaluate the signatures of the 28 HP-related prognostic genes. The overall survival rate in the high-HPscore group was poor and immunological surveillance was reduced, whereas the low-HPscore group had a survival advantage and was related to the inflammatory response. HPscore was also strongly correlated with the tumour stage, TME cell infiltration and stemness. The qRT-PCR results showed that DOCK4 expression level of 28 HP-related prognostic genes was higher in gastric cancer tissues than in adjacent tissues.
HP signatures play a crucial role in the TME and tumourigenesis. HPscore evaluation of a single tumour sample can help identify the TME characteristics and the carcinogenic mechanism of GC patients infected with HP, based on which personalized treatment can be administered.
幽门螺杆菌（HP）感染是胃癌（GC）的主要病因之一。然而，HP与肿瘤微环境（TME）之间的相互作用及其致癌机制仍不清楚。
基于HP感染相关基因标志物和HP感染样本数据集，采用风险法和非负矩阵分解（NMF）算法鉴定HP相关预后基因。运用主成分分析（PCA）算法构建HP评分系统。使用“limma”R包确定差异表达基因。此外，使用“xCell”和“GSVA”等R包分析HP评分与肿瘤微环境的关系。最后，进行定量实时聚合酶链反应（qRT-PCR）以验证28个HP相关预后基因在组织中的表达水平。
我们成功鉴定出28个HP相关预后基因，这些基因可准确对GC人群进行分类。不同亚组（高、低风险和cluster_1、2）之间的生存率存在显著差异。此后，构建了HP评分系统以评估这28个HP相关预后基因的特征。高HP评分组的总生存率较差，免疫监视降低，而低HP评分组具有生存优势且与炎症反应相关。HP评分也与肿瘤分期、TME细胞浸润和干性密切相关。qRT-PCR结果显示，28个HP相关预后基因中的DOCK4在胃癌组织中的表达水平高于癌旁组织。
HP特征在TME和肿瘤发生中起关键作用。对单个肿瘤样本进行HP评分评估有助于识别感染HP的GC患者的TME特征和致癌机制，据此可进行个性化治疗。
