Li Hailin, Han Guangyu, Li Xing, Li Bowen, Wu Bo, Jin Hongyuan, Wu Lingli, Wang Wei
Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China.
Department of Oncology and Laparoscopy Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Oncol. 2021 Jun 10;11:649980. doi: 10.3389/fonc.2021.649980. eCollection 2021.
BACKGROUND: MAPK-RAP1A signaling, which is involved in cancer progression, remains to be defined. Upregulation of MAPK-RAP1A signaling accounts for most cancers that harbor high incident rate, such as non-small cell lung cancer (NSCLC) and pancreatic cancer, especially in hepatocellular carcinoma (HCC). MAPK-RAP1A signaling plays an important function as clinical diagnosis and prognostic value in cancers, and the role of MAPK-RAP1A signaling related with immune infiltration for HCC should be elucidated. METHODS: Microarray data and patient cohort information from The Cancer Genome Atlas (TCGA; n = 425) and International Cancer Genome Consortium (ICGC; n = 405) were selected for validation. The Cox regression and least absolute shrinkage and selection operator (LASSO) were used to construct a clinical prognostic model in this analysis and validation study. We also tested the area under the curve (AUC) of the risk signature that could reflect the status of predictive power by determining model. MAPK-RAP1A signaling is also associated with tumor-infiltrating immune cells (TICs) as well as clinical parameters in HCC. The GSEA and CIBERSORT were used to calculate the proportion of TICs, which should be beneficial for the clinical characteristics (clinical stage, distant metastasis) and positively correlated with the survival of HCC patients. RESULTS: HCC patients with enrichment of MAPK-RAP1A signaling were associated with clinical characteristics and favorable T cell gamma delta (V T cells), and STMN1, RAP1A, FLT3, HSPA8, ANGPT2, and PGF were used as candidate biomarkers for risk scores of HCC. To determine the molecular mechanism of this signature gene association, Gene Set Enrichment Analysis (GSEA) was proposed. Cytokine-cytokine receptor interaction, TGF- signaling pathway, and Intestinal immune network for IgA production gene sets were closely related in MAPK-RAP1A gene sets. Thus, we established a novel prognostic prediction of HCC to deepen learning of MAPK-RAP1A signaling pathways. CONCLUSION: Our findings demonstrated that HCC patients with enrichment of MAPK-RAP1A signaling were associated with clinical characteristics and favorable T cell gamma delta (V T cells), which may be a novel prognostic prediction of HCC.
背景：参与癌症进展的丝裂原活化蛋白激酶- RAP1A信号传导仍有待明确。丝裂原活化蛋白激酶- RAP1A信号传导的上调在大多数发病率较高的癌症中都有体现，如非小细胞肺癌（NSCLC）和胰腺癌，尤其是在肝细胞癌（HCC）中。丝裂原活化蛋白激酶- RAP1A信号传导在癌症的临床诊断和预后价值方面发挥着重要作用，并且应阐明其与HCC免疫浸润相关的作用。 方法：选择来自癌症基因组图谱（TCGA；n =第425例）和国际癌症基因组联盟（ICGC；n =第405例）的微阵列数据和患者队列信息进行验证。在本分析和验证研究中，使用Cox回归和最小绝对收缩和选择算子（LASSO）构建临床预后模型。我们还通过确定模型来测试能够反映预测能力状态的风险特征曲线下面积（AUC）。丝裂原活化蛋白激酶- RAP1A信号传导也与HCC中的肿瘤浸润免疫细胞（TIC）以及临床参数相关。使用基因集富集分析（GSEA）和CIBERSORT计算TIC的比例，这对于临床特征（临床分期、远处转移）应该是有益的，并且与HCC患者的生存率呈正相关。 结果：丝裂原活化蛋白激酶- RAP1A信号传导富集的HCC患者与临床特征以及良好的T细胞γδ（V T细胞）相关，并且STMN1、RAP1A、FLT3、HSPA8、ANGPT第2和PGF被用作HCC风险评分的候选生物标志物。为了确定这种特征基因关联的分子机制，提出了基因集富集分析（GSEA）。细胞因子-细胞因子受体相互作用、转化生长因子信号通路以及IgA产生基因集的肠道免疫网络在丝裂原活化蛋白激酶- RAP1A基因集中密切相关。因此，我们建立了一种新的HCC预后预测方法，以加深对丝裂原活化蛋白激酶- RAP1A信号通路的了解。 结论：我们的研究结果表明，丝裂原活化蛋白激酶- RAP1A信号传导富集的HCC患者与临床特征以及良好的T细胞γδ（V T细胞）相关，这可能是一种新的HCC预后预测方法。
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