Ma Junren, Meng Yan, Zhou Xin, Guo Limei, Fu Wei
Department of General Surgery, Peking University Third Hospital, Beijing, China.
Peking University Third Hospital Cancer Center, Beijing, China.
Front Surg. 2022 Mar 17;9:819018. doi: 10.3389/fsurg.2022.819018. eCollection 2022.
This study is based on the Surveillance, Epidemiology, and End Results (SEER) program to explore the prognostic differences between signet-ring cell carcinoma (SRC) and intestinal-type gastric carcinoma (ITGC). This study is also based on gene sequencing data from The Cancer Genome Atlas (TCGA) to identify unique genetic contributions to the prognostic differences between the two subtypes of gastric cancer.
The clinical data were based on the SEER database from 2004 to 2015. Kaplan-Meier (KM) curves were used to compare 5-year overall survival (OS), and Cox regression was used for univariate and multivariate analyses. Gene expression profiles were obtained from TCGA database, and differentially expressed genes (DEGs) were screened. Functional enrichment analysis, protein interaction and survival analysis will be further carried out. Genes of interest were verified by the Human Protein Atlas, immunohistochemistry, and encyclopedia of Cancer Cell Lines (CCLE). The relationship between genes of interest and immune cell infiltration was also analyzed by Tumor Immune Estimation Resource (TIMER).
Compared with ITGC patients, SRC patients were more likely to be female, tended to be younger, and have a greater tumor distribution in the middle and lower stomach ( < 0.01). SRCs showed a significantly better prognosis than ITGCs ( < 0.01) in early gastric cancer (EGC), while the prognosis of SRCs was significantly worse than ITGCs ( < 0.05) in advanced gastric cancer (AGC). A total of 256 DEGs were screened in SRCs compared to ITGCs, and the enrichment analysis and protein interactions revealed that differential genes were mainly related to extracellular matrix organization. Thrombospondin1 (THBS1) and serpin peptidase inhibitor, clade E, member 1 (SERPINE1) are significantly differentially expressed between SRC and ITGC, which has been preliminarily verified by immunohistochemistry and open-source databases. THBS1 and SERPINE1 are also associated with multiple immune cell infiltrates in gastric cancer.
There were significant differences in the clinicopathological features and prognosis between SRC and ITGC. These results suggest that SRC and ITGC may be two distinct types of tumors with different pathogeneses. We found many codifferentially expressed genes and important pathways between SRC and ITGC. THBS1 and SERPINE1 were significantly differentially expressed in the two types of gastric cancer, and may have potentially important functions.
本研究基于监测、流行病学和最终结果（SEER）计划，探讨印戒细胞癌（SRC）和肠型胃癌（ITGC）之间的预后差异。本研究还基于癌症基因组图谱（TCGA）的基因测序数据，以确定对两种胃癌亚型预后差异的独特遗传贡献。
临床数据基于2004年至2015年的SEER数据库。采用Kaplan-Meier（KM）曲线比较5年总生存率（OS），并使用Cox回归进行单因素和多因素分析。从TCGA数据库获取基因表达谱，并筛选差异表达基因（DEG）。将进一步进行功能富集分析、蛋白质相互作用和生存分析。通过人类蛋白质图谱、免疫组织化学和癌细胞系百科全书（CCLE）对感兴趣的基因进行验证。还通过肿瘤免疫估计资源（TIMER）分析感兴趣的基因与免疫细胞浸润之间的关系。
与ITGC患者相比，SRC患者更可能为女性，年龄倾向于更小，且肿瘤在胃中下部的分布更多（<0.01）。在早期胃癌（EGC）中，SRC的预后明显优于ITGC（<0.01），而在进展期胃癌（AGC）中，SRC的预后明显差于ITGC（<0.05）。与ITGC相比，SRC中共筛选出256个DEG，富集分析和蛋白质相互作用显示差异基因主要与细胞外基质组织有关。血小板反应蛋白1（THBS1）和丝氨酸蛋白酶抑制剂E族成员1（SERPINE1）在SRC和ITGC之间有显著差异表达，已通过免疫组织化学和开源数据库初步验证。THBS1和SERPINE1也与胃癌中的多种免疫细胞浸润有关。
SRC和ITGC在临床病理特征和预后方面存在显著差异。这些结果表明，SRC和ITGC可能是两种具有不同发病机制的不同类型肿瘤。我们发现SRC和ITGC之间有许多共同差异表达的基因和重要途径。THBS1和SERPINE1在两种类型的胃癌中均有显著差异表达，可能具有潜在的重要功能。
