Liu Chuan, Hu Chuan, Li Zhi, Feng Jing, Huang Jiale, Yang Bowen, Wen Ti
Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.
Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.
Cancer Cell Int. 2020 Jun 30;20:279. doi: 10.1186/s12935-020-01368-8. eCollection 2020.
Alternative splicing (AS) may cause structural and functional variations in the protein to promote the proliferation of tumor cells. However, there is no comprehensive analysis of the clinical significance of AS in -negative gastric cancer (HP GC).
The clinical, gene expression profile data and AS events of 138 HP GC patients were obtained from the database named the cancer genome atlas. Differently expressed AS (DEAS) events were determined by a comparison of the PSI values between HP GC samples and adjacent normal samples. Unsupervised clustering analysis, proportional regression and Kaplan-Meier analysis were used to explore the association between clinical data and immune features and to establish two nomograms about the prognosis of HP GC. Finally, splicing networks were constructed using Cytoscape.
A total of 48141 AS events and 1041 DEAS events were found in HP GC. Various functions and pathways of DEAS events parent genes were enriched, such as cell-substrate junction, cell leading edge, focal adhension, and AMPK signaling. Seven overall survival (OS)-related and seven disease-free survival (DFS)-related AS events were used to construct the prognostic signatures. Based on the independent prognostic factors, two nomograms were established and showed excellent performance. Then, splicing regulatory networks among the correlations suggested that splicing factors were significantly associated with prognostic DEASs. Finally, the unsupervised clustering analysis revealed that DEAS-based clusters were associated with clinical characteristics, tumor microenvironment, tumor mutation burden, and immune features.
Seven OS-related and seven DFS-related AS events have been found to be correlated with the prognosis of HP GC and can be used as prognostic factors to establish an effective nomogram.
可变剪接（AS）可能导致蛋白质的结构和功能变异，从而促进肿瘤细胞的增殖。然而，目前尚无关于幽门螺杆菌阴性胃癌（HP GC）中AS临床意义的综合分析。
从癌症基因组图谱数据库中获取138例HP GC患者的临床、基因表达谱数据和AS事件。通过比较HP GC样本与相邻正常样本的PSI值来确定差异表达的AS（DEAS）事件。采用无监督聚类分析、比例回归分析和Kaplan-Meier分析来探索临床数据与免疫特征之间的关联，并建立两个关于HP GC预后的列线图。最后，使用Cytoscape构建剪接网络。
在HP GC中总共发现了48141个AS事件和1041个DEAS事件。DEAS事件亲本基因的各种功能和通路得到富集，如细胞-基质连接、细胞前沿、粘着斑和AMPK信号通路。使用7个与总生存期（OS）相关和7个与无病生存期（DFS）相关的AS事件来构建预后特征。基于独立预后因素，建立了两个列线图，其表现优异。然后，相关性之间的剪接调控网络表明，剪接因子与预后DEAS显著相关。最后，无监督聚类分析显示，基于DEAS的聚类与临床特征、肿瘤微环境、肿瘤突变负荷和免疫特征相关。
已发现7个与OS相关和7个与DFS相关的AS事件与HP GC的预后相关，可作为预后因素来建立有效的列线图。
