Microsatellite instability (MSI) is emerging as a promising subtype related to immunotherapy in gastric cancer (GC). However, the underlying mechanism between MSI and microsatellite stability (MSS) remains unclear. In this study, we conducted a weighted gene co-expression network analysis and found that the expression of heterogeneous nuclear ribonucleoprotein L (HNRNPL) was significantly increased in MSI GC compared with MSS GC. This finding was further validated in public GC cohorts and commercialized human GC tissue microarray. The significant negative correlation with the expression of mismatch repair protein mutL homolog 1 (MLH1) may be one of the potential mechanisms for the upregulation of HNRNPL expression in MSI GC (R = −0.689, p = 8.59e–11). In addition, HNRNPL expression was markedly upregulated in GC tissues compared with adjacent normal tissues. High HNRNPL expression also predicted a poor prognosis in GC patients. Finally, gene set enrichment analysis revealed that high HNRNPL MSI GC samples were highly positive associated with the biological functions of inflammation and cell proliferation, such as interferon gamma response, MYC targets, E2F targets, and G2/M checkpoints. In conclusion, HNRNPL could be a new MSI-associated prognostic biomarker in GC and could be a new target for the MSI GC treatment.

中文翻译：

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HNRNPL 被鉴定和验证为与人类胃癌微卫星不稳定性相关的预后生物标志物

微卫星不稳定性（MSI）正在成为与胃癌（GC）免疫治疗相关的有前途的亚型。然而，MSI与微卫星稳定性（MSS）之间的潜在机制仍不清楚。在本研究中，我们进行了加权基因共表达网络分析，发现与 MSS GC 相比，MSI GC中异质核核糖核蛋白 L ( HNRNPL )的表达显着增加。这一发现在公共 GC 队列和商业化的人类 GC 组织微阵列中得到了进一步验证。与错配修复蛋白mutL同源物1（MLH1）表达显着负相关可能是MSI GC（R ）中HNRNPL表达上调的潜在机制之一。 = -0.689，p  = 8.59e–11）。此外，与邻近的正常组织相比，HNRNPL在 GC 组织中的表达显着上调。高HNRNPL表达也预示着 GC 患者的预后不良。最后，基因集富集分析显示，高HNRNPL MSI GC 样本与炎症和细胞增殖的生物学功能呈高度正相关，例如干扰素 γ 反应、MYC 目标、E2F 目标和 G2/M 检查点。总之，HNRNPL可能是 GC 中新的 MSI 相关预后生物标志物，并可能成为 MSI GC 治疗的新靶点。