School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, HBNI, P.O. Jatni, Khurda, 752050, Odisha, India.
School of Biological Sciences, NISER, Room No.- 203, P.O. Jatni, Khurda, Odisha, 752050, India.
Sci Rep. 2021 Nov 18;11(1):22505. doi: 10.1038/s41598-021-01665-w.
FRG1 has a role in tumorigenesis and angiogenesis. Our preliminary analysis showed that FRG1 mRNA expression is associated with overall survival (OS) in certain cancers, but the effect varies. In cervix and gastric cancers, we found a clear difference in the OS between the low and high FRG1 mRNA expression groups, but the difference was not prominent in breast, lung, and liver cancers. We hypothesized that FRG1 expression level could affect the functionality of the correlated genes or vice versa, which might mask the effect of a single gene on the OS analysis in cancer patients. We used the multivariate Cox regression, risk score, and Kaplan Meier analyses to determine OS in a multigene model. STRING, Cytoscape, HIPPIE, Gene Ontology, and DAVID (KEGG) were used to deduce FRG1 associated pathways. In breast, lung, and liver cancers, we found a distinct difference in the OS between the low and high FRG1 mRNA expression groups in the multigene model, suggesting an independent role of FRG1 in survival. Risk scores were calculated based upon regression coefficients in the multigene model. Low and high-risk score groups showed a significant difference in the FRG1 mRNA expression level and OS. HPF1, RPL34, and EXOSC9 were the most common genes present in FRG1 associated pathways across the cancer types. Validation of the effect of FRG1 mRNA expression level on these genes by qRT-PCR supports that FRG1 might be an upstream regulator of their expression. These genes may have multiple regulators, which also affect their expression, leading to the masking effect in the survival analysis. In conclusion, our study highlights the role of FRG1 in the survivability of cancer patients in tissue-specific manner and the use of multigene models in prognosis.
FRG1 在肿瘤发生和血管生成中起作用。我们的初步分析表明，FRG1 mRNA 的表达与某些癌症的总生存期（OS）相关，但效果不同。在宫颈癌和胃癌中，我们发现低 FRG1 mRNA 表达组和高 FRG1 mRNA 表达组之间的 OS 有明显差异，但在乳腺癌、肺癌和肝癌中差异不显著。我们假设 FRG1 表达水平可能会影响相关基因的功能，反之亦然，这可能会掩盖单个基因对癌症患者 OS 分析的影响。我们使用多变量 Cox 回归、风险评分和 Kaplan-Meier 分析来确定多基因模型中的 OS。STRING、Cytoscape、HIPPIE、Gene Ontology 和 DAVID（KEGG）用于推断 FRG1 相关通路。在乳腺癌、肺癌和肝癌中，我们发现多基因模型中低 FRG1 mRNA 表达组和高 FRG1 mRNA 表达组之间的 OS 有明显差异，表明 FRG1 在生存中具有独立作用。风险评分是根据多基因模型中的回归系数计算的。低风险评分组和高风险评分组在 FRG1 mRNA 表达水平和 OS 上有显著差异。HPF1、RPL34 和 EXOSC9 是 FRG1 相关通路中最常见的基因。qRT-PCR 验证 FRG1 mRNA 表达水平对这些基因的影响支持 FRG1 可能是其表达的上游调节剂。这些基因可能有多个调节因子，也会影响它们的表达，从而导致生存分析中的掩盖效应。总之，我们的研究强调了 FRG1 在组织特异性方式下对癌症患者生存能力的作用以及多基因模型在预后中的应用。
