Yang Yalan, Jiang Li, Wang Sixue, Chen Huan, Yi Mingyu, Wu Yuqing, Li Zeying, Fang Xiaoling
Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China.
Transl Cancer Res. 2022 Sep;11(9):3187-3208. doi: 10.21037/tcr-22-502.
The gene encodes an important nucleoside metabolism enzyme which is a rate-limiting enzyme for chemotherapeutic drug metabolism. Previous studies have shown that is highly expressed in many different tumors, promoting invasiveness and progression, and that it helps to predict the response to chemotherapeutic drugs. However, the role of in tumor immunity and prognosis remains largely unclear. The purpose of this pan-cancer analysis was to acquire more data on the function of function and its clinical significance.
To access the expression, we accessed datasets from The Cancer Genome Atlas (TCGA), Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Cancer Cell Line Encyclopedia (CCLE) databases, and analyzed its differential expression between paired tumor and normal samples. We employed PrognoScan and Kaplan-Meier plotter for survival analyses. mutations were analyzed using cBioPortal. Correlations of with tumor stage, tumor mutational burden (TMB), microsatellite instability (MSI), immune checkpoint genes (ICGs), and immune cell infiltration were estimated via bioinformatics tools and methods. The CellMiner database was used to predict drug response. Gene set enrichment analysis (GSEA) was applied to explore the biological functions of in different tumors.
Our results indicated that was overexpressed and also significantly associated with a worse prognosis in several human cancers, such as kidney clear cell carcinoma (KIRC) and lower grade glioma (LGG). was also associated with TMB, MSI, and ICGs across a variety of malignancies. was most significantly correlated with immune cell infiltration in five tumors, namely, breast cancer (BRCA), cervical cancer (CESC), KIRC, skin cutaneous melanoma (SKCM), and stomach adenocarcinoma (STAD). Moreover, expression predicted sensitivity to chemotherapy drugs and also influenced relevant biological pathways, according to enrichment analysis.
According to the results of this comprehensive analysis, is associated with prognosis and tumor immunology, which might make it be a potential therapeutic target for cancer treatment.
该基因编码一种重要的核苷代谢酶，它是化疗药物代谢的限速酶。先前的研究表明，该基因在许多不同肿瘤中高表达，促进侵袭和进展，并且有助于预测对化疗药物的反应。然而，该基因在肿瘤免疫和预后中的作用仍 largely 不清楚。这项泛癌分析的目的是获取更多关于该基因功能及其临床意义的数据。
为了评估该基因的表达，我们从癌症基因组图谱（TCGA）、Oncomine、基因表达谱交互式分析（GEPIA）、癌细胞系百科全书（CCLE）数据库中获取数据集，并分析其在配对肿瘤和正常样本之间的差异表达。我们使用 PrognoScan 和 Kaplan-Meier 绘图仪进行生存分析。使用 cBioPortal 分析该基因的突变。通过生物信息学工具和方法估计该基因与肿瘤分期、肿瘤突变负担（TMB）、微卫星不稳定性（MSI）、免疫检查点基因（ICG）和免疫细胞浸润的相关性。使用 CellMiner 数据库预测药物反应。应用基因集富集分析（GSEA）来探索该基因在不同肿瘤中的生物学功能。
我们的结果表明，该基因在几种人类癌症中过表达，并且也与较差的预后显著相关，如肾透明细胞癌（KIRC）和低级别胶质瘤（LGG）。该基因在多种恶性肿瘤中也与 TMB、MSI 和 ICG 相关。该基因在五种肿瘤中与免疫细胞浸润最显著相关，即乳腺癌（BRCA）、宫颈癌（CESC）、KIRC、皮肤黑色素瘤（SKCM）和胃腺癌（STAD）。此外，根据富集分析，该基因的表达预测了对化疗药物的敏感性，并且还影响了相关的生物学途径。
根据这项综合分析的结果，该基因与预后和肿瘤免疫学相关，这可能使其成为癌症治疗的潜在治疗靶点。
