Li Yansen, Lin Yilin, Zhao Long, Yang Changjiang, Wang Bo, Gao Zhidong, Ye Yingjiang, Wang Shan, Shen Zhanlong
Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.; Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing, China; Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.; Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing, China.
Transl Oncol. 2023 Oct;36:101737. doi: 10.1016/j.tranon.2023.101737. Epub 2023 Jul 19.
Gastric cancer is one of the most common malignant tumors in the world. Alpha fetoprotein (AFP)-positive gastric cancer (AFPP-GC) is considered a special entity among gastric cancers. There is still controversy regarding the clinicopathological characteristics and prognosis of AFPP-GC, and the potential mechanism underlying its high malignant potential is still unclear. A comprehensive description of AFPP-GC genomic characteristics and regulatory mechanisms is lacking. This study analyzed the pathological characteristics and prognosis of AFPP-GC by utilizing clinical samples. The results showed that AFPP-GC has a poor prognosis and a high of risk liver metastasis. Tissue transcriptome sequencing showed that genes with high expression in AFPP-GC were involved in the activation of various cancer pathways, and genes with low expression were involved in the immune response. Single-sample gene set enrichment analysis showed that overexpression of AFP in AFPP-GC significantly inhibited the infiltration of CD8 T cells. To further explore the genomic characteristics of AFPP-GC, the signaling pathway by which AFP regulates the invasion and metastasis of AFPP-GC cells was discussed. The results showed that AFPP-GC may promote cell invasion by regulating the PTEN/AKT1/SOX5/CES1 signaling axis. This study reveals the molecular mechanism underlying the increased malignant potential of AFPP-GC vs. AFP-negative gastric cancer (AFPN-GC). This provides important information for individualized treatment of AFPP-GC.
胃癌是世界上最常见的恶性肿瘤之一。甲胎蛋白（AFP）阳性胃癌（AFPP-GC）被认为是胃癌中的一种特殊类型。关于AFPP-GC的临床病理特征和预后仍存在争议，其高恶性潜能的潜在机制仍不清楚。目前缺乏对AFPP-GC基因组特征和调控机制的全面描述。本研究通过利用临床样本分析了AFPP-GC的病理特征和预后。结果显示，AFPP-GC预后较差，肝转移风险高。组织转录组测序表明，在AFPP-GC中高表达的基因参与了各种癌症通路的激活，而低表达的基因参与了免疫反应。单样本基因集富集分析表明，AFPP-GC中AFP的过表达显著抑制了CD8 T细胞的浸润。为了进一步探索AFPP-GC的基因组特征，讨论了AFP调节AFPP-GC细胞侵袭和转移的信号通路。结果显示，AFPP-GC可能通过调节PTEN/AKT1/SOX5/CES1信号轴促进细胞侵袭。本研究揭示了AFPP-GC与AFP阴性胃癌（AFPN-GC）相比恶性潜能增加的分子机制。这为AFPP-GC的个体化治疗提供了重要信息
