DataSheet2_Pan-cancer analysis of SERPINE family genes as biomarkers of cancer prognosis and response to therapy.PDF

Background: Serine protease inhibitor E (SERPINE) family genes participate in the tumor growth, cancer cell survival and metastasis. However, the SERPINE family members role in the prognosis and their clinical therapeutic potentials in various human cancer types have not been elaborately explored.
Methods: We preliminarily analyzed expression levels and prognostic values of SERPINE family genes, and investigated the correlation between SERPINEs expression and tumor microenvironment (TME), Stemness score, clinical characteristic, immune infiltration, tumor mutational burden (TMB), immune subtype, and drug sensitivity in pan-cancer, which based on updated public databases and integrated some bioinformatics analysis methods. In addition, we conducted the enrichment analysis of SERPINEs from DAVID and KOBAS databases.
Results: SERPINE1, SERPINE2, and SERPINE3 expression were upregulated in nine cancers, twelve cancers, and six cancers, respectively. The expression of SERPINE family genes was associated with the prognosis in several cancers from The Cancer Genome Atlas (TCGA). Furthermore, SERPINE family genes expression also had a significant relation to stromal and immune scores, and RNA stemness score and DNA stemness score in pan-cancer. SERPINE1 and SERPINE2 expression significantly increased in tumor advanced stage in colon adenocarcinoma (COAD). Results showed that SERPINE1 and SERPINE2 expression were negatively related with B cells and Monocytes, respectively. SERPINE2 expression had a significantly positive relation with B cells and Macrophages. In terms of TMB, SERPINE1, SERPINE2, and SERPINE3 were found to associated with TMB in seven cancers, fourteen cancers, and four cancers, respectively. Moreover, all SERPINE gene family members were significantly correlated with immune subtypes. SERPINE1 expression had a significantly positive or negative correlation with drug sensitivity.
Conclusion: The study indicated the great potential of SERPINE family genes as biomarkers for prognosis and provided valuable strategies for further investigation of SERPINE family genes as potential targets in cancer.

研究背景：丝氨酸蛋白酶抑制剂E（SERPINE）家族基因参与肿瘤生长、癌细胞存活及转移过程。然而，目前尚未对该家族成员在多种人类癌症中的预后价值及其临床治疗潜力进行详尽系统的探究。
研究方法：本研究首先分析了SERPINE家族基因的表达水平与预后价值，并基于更新后的公共数据库，整合多种生物信息学分析方法，全面探究了SERPINE家族基因表达与肿瘤微环境（Tumor Microenvironment, TME）、干性评分、临床特征、免疫浸润、肿瘤突变负荷（Tumor Mutational Burden, TMB）、免疫亚型以及药物敏感性在泛癌分析中的关联。此外，本研究还通过DAVID和KOBAS数据库对SERPINE家族基因开展了富集分析。
研究结果：SERPINE1、SERPINE2与SERPINE3的表达分别在9种、12种和6种癌症中呈上调趋势。癌症基因组图谱（TCGA）数据库的数据分析显示，SERPINE家族基因的表达与多种癌症的预后显著相关。进一步研究表明，泛癌分析中，SERPINE家族基因的表达与基质评分、免疫评分、RNA干性评分及DNA干性评分均存在显著关联。在结肠腺癌（COAD）中，SERPINE1与SERPINE2的表达在肿瘤晚期阶段显著升高。结果显示，SERPINE1与SERPINE2的表达分别与B细胞和单核细胞呈负相关；SERPINE2的表达则与B细胞及巨噬细胞呈显著正相关。在肿瘤突变负荷（TMB）层面，SERPINE1、SERPINE2与SERPINE3的表达分别在7种、14种和4种癌症中与TMB存在关联。此外，所有SERPINE家族基因成员均与免疫亚型显著相关。SERPINE1的表达与药物敏感性呈显著正相关或负相关。
研究结论：本研究揭示了SERPINE家族基因作为预后生物标志物的巨大潜力，并为后续将该家族基因作为癌症潜在治疗靶点的研究提供了极具价值的参考策略。