He Shuo, Liu Qing, Luo Shujuan, Cai Bangwu, Chen Jiao, Peng Tianyuan, Wang Wei, Liu Tao, Lu Xiaomei, Zheng Shutao
State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China; Department of Pathology, Basic Medicine College, Xinjiang Medical University, Urumqi 830017, China.
State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China.
Hum Immunol. 2024 Nov;85(6):111167. doi: 10.1016/j.humimm.2024.111167. Epub 2024 Oct 28.
Recent studies have increasingly focused on PIK3CA mutations in esophageal squamous cell carcinoma (ESCC); however, the clinicopathological significance of these mutations within the tumor microenvironment remains underexplored. This study aimed to evaluate and compare the clinicopathological significance of mutated PIK3CA in ESCC using in silico analyses of the ESCC dataset from the TCGA database. We assessed prognosis, differential expression, correlation with immune cell infiltration and immune checkpoint expression, heterogeneity, and drug sensitivity in comparison with wild-type PIK3CA. Our findings revealed that PIK3CA mutation is associated with increased tumor mutation burden and significantly correlated with the infiltration of CD4 naive and effector memory CD4 T cells. Additionally, ESCC cells harboring PIK3CA mutations exhibited reduced sensitivity to p38/JNK MAPK inhibitors compared to those with wild-type PIK3CA. Collectively, our in silico analysis suggests that mutational PIK3CA plays a role in resistance to p38 and JNK MAPK inhibitors in ESCC.
最近的研究越来越关注食管鳞状细胞癌（ESCC）中的PIK3CA突变；然而，这些突变在肿瘤微环境中的临床病理意义仍未得到充分探索。本研究旨在通过对来自TCGA数据库的ESCC数据集进行电子分析，评估和比较ESCC中突变型PIK3CA的临床病理意义。与野生型PIK3CA相比，我们评估了预后、差异表达、与免疫细胞浸润和免疫检查点表达的相关性、异质性以及药物敏感性。我们的研究结果显示，PIK3CA突变与肿瘤突变负担增加相关，并且与CD4幼稚和效应记忆CD4 T细胞的浸润显著相关。此外，与野生型PIK3CA的ESCC细胞相比，携带PIK3CA突变的ESCC细胞对p38/JNK MAPK抑制剂的敏感性降低。总体而言，我们的电子分析表明，突变型PIK3CA在ESCC对p38和JNK MAPK抑制剂的耐药中起作用。
