Background/Objectives: Gastric cancer (GC) is a highly aggressive malignancy with diverse molecular subtypes. While microsatellite instability (MSI) GC generally carries a favorable prognosis, a subset of patients experiences poor outcomes, highlighting the need for refined prognostic markers.Methods:This study utilized transcriptomic and clinical data from two independent cohorts, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG), to identify novel prognostic genes in MSI-GC. Results: Through rigorous survival analysis, we identified highMAP4K4expression (MAP4K4high) as an independent and robust predictor of poor overall survival (OS) and disease-free survival (DFS) specifically within the MSI-GC subtype.MAP4K4highwas associated with increased hazard ratios for both OS and DFS in both cohorts, even after adjusting for clinicopathological factors. Further analysis revealed thatMAP4K4highMSI-GC tumors exhibit a distinct molecular profile characterized by increased extracellular matrix remodeling, epithelial–mesenchymal transition, and a microenvironment enriched in monocytes and cancer-associated fibroblasts (CAFs). Notably, a subgroup of MSI-GC patients with a CIN-like phenotype and highMAP4K4expression exhibited particularly dismal outcomes. Conclusions: Our findings establishMAP4K4as a promising prognostic biomarker for risk stratification in MSI-GC and suggest its potential role in driving aggressive tumor behavior through modulation of the tumor microenvironment.
背景/目的：胃癌是一种高度侵袭性的恶性肿瘤，具有多种分子亚型。虽然微卫星不稳定性胃癌通常预后较好，但部分患者预后不良，这凸显了对精细化预后标志物的需求。 方法：本研究利用来自癌症基因组图谱和亚洲癌症研究组两个独立队列的转录组学及临床数据，旨在识别微卫星不稳定性胃癌中的新型预后基因。 结果：通过严格的生存分析，我们发现高MAP4K4表达是微卫星不稳定性胃癌亚型中总体生存期和无病生存期不良的独立且稳健的预测因子。在两个队列中，即使在校正临床病理因素后，MAP4K4高表达仍与总体生存期和无病生存期的风险比增加相关。进一步分析显示，MAP4K4高表达的微卫星不稳定性胃癌肿瘤具有独特的分子特征，表现为细胞外基质重塑增强、上皮-间质转化以及富含单核细胞和癌症相关成纤维细胞的微环境。值得注意的是，具有染色体不稳定性样表型且MAP4K4高表达的微卫星不稳定性胃癌患者亚组预后尤其不良。 结论：我们的研究结果确立了MAP4K4作为微卫星不稳定性胃癌风险分层的一个有前景的预后生物标志物，并提示其可能通过调节肿瘤微环境驱动侵袭性肿瘤行为。
肿瘤(癌症)患者之家