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Differential prognostic impact and potential molecular mechanisms of PCDHGA12 expression in lung adenocarcinoma and squamous cell carcinoma

腺癌 医学 基底细胞 肿瘤科 病理 鉴别诊断 癌症研究 鳞癌 内科学 癌症
作者
Xiangqian Xu,Jun Zhang,Tsun‐Wen Yao,Xiaokai Zhao,Qingyuan Wu,Chenghua Lu,Xiaoyan Guo,Shiyun Xie,Lei Qiu,Rongrong Bi,Hui-Guang Xue
出处
期刊:International Immunopharmacology [Elsevier]
卷期号:139: 112727-112727
标识
DOI:10.1016/j.intimp.2024.112727
摘要

Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), subtypes of non-small cell lung cancer (NSCLC), exhibit distinct characteristics. The expression and prognostic significance of Protocadherin Gamma Subfamily A, 12 (PCDHGA12) in NSCLC remain unexplored. This study analyzed transcriptomic and genomic datasets from TCGA to investigate PCDHGA12 expression and its prognostic relevance in LUAD and LUSC. We found PCDHGA12 mRNA and protein levels were downregulated in both LUAD and LUSC tissues compared to adjacent non-cancerous tissues, with high PCDHGA12 expression correlating with lower overall survival in LUSC but not in LUAD. GSEA revealed a unique enrichment pattern associated with PCDHGA12 low expression in LUSC, especially in the DNA repair pathway. Co-expression analysis showed associations of PCDHGA12 with focal adhesion and the PI3K-AKT pathway in LUAD, and additionally with ECM-receptor interaction in LUSC. Hub gene prognosis analysis identified genes correlated with prognosis only in LUSC, reflecting PCDHGA12's influence. Mutation analysis linked with PCDHGA12 identified differential mutations in SPTA1, KEAP1, and TNR in LUAD, and a notable NAV3 mutation in LUSC. Additionally, immuno-infiltration analysis reveals a positive correlation between PCDHGA12 expression and immune cell infiltration. Specifically, lower PCDHGA12 expression in LUSC is associated with higher levels of CD8 T cells and DCs, lower levels of Tregs and M0 macrophages, and increased expression of HMGB1 and TNFRSF18. These genetic and immunological differences may account for the significant prognostic disparity of PCDHGA12 levels between LUAD and LUSC. Further experimental studies are essential to validate these associations and investigate potential targeted and immunotherapeutic strategies.
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