Abstract

Background

Sirtuin 5 (SIRT5) is a promising therapeutic target involved in regulating multiple metabolic pathways in cells and organisms. The role of SIRT5 in cancer is currently unclear, and a comprehensive systematic pan-cancer analysis is required to explore its value in diagnosis, prognosis, and immune function.

Methods

We investigated the role of SIRT5 in tumorigenesis, diagnosis, prognosis, metabolic pathways, the immune microenvironment, and pan-cancer therapeutic response. Moreover, we explored chemicals affecting the expression of SIRT5 and computed the relationship between SIRT5 and drug sensitivity. Finally, the role of SIRT5 in melanoma was analyzed using a series of experiments in vitro and in vivo.

Results

We found that SIRT5 is differentially expressed and shows early diagnostic value in various tumors and that somatic cell copy number alterations and DNA methylation contribute to its aberrant expression. SIRT5 expression correlates with clinical features. Besides, it is negatively (positively) correlated with several metabolic pathways and positively (negatively) correlated with several important metastasis-related and immune-related pathways. High SIRT5 expression predicts poor (or good) prognosis in various tumors and can affect drug sensitivity. We also demonstrated that SIRT5 expression significantly correlates with immunomodulator-associated molecules, lymphocyte subpopulation infiltration, and immunotherapeutic response biomarkers. In addition, we showed that SIRT5 is differentially expressed in immunotherapy cohorts. In addition, we explored various chemicals that may affect SIRT5 expression. In conclusion, we demonstrated that SIRT5 is a key pathogenic gene that promotes melanoma progression.

Conclusion

Our study provides a systematic analysis of SIRT5 and its regulatory genes. SIRT5 has excellent diagnostic and prognostic capabilities for many cancers. This may remodel the tumor microenvironment. The potential of SIRT5-based cancer therapies is emphasized and helps predict the response to immunotherapy.

中文翻译：

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综合泛癌分析表明 SIRT5 是预后和免疫治疗反应的预测生物标志物

摘要

背景

Sirtuin 5 (SIRT5) 是一个有前途的治疗靶点，参与调节细胞和生物体的多种代谢途径。SIRT5在癌症中的作用目前尚不清楚，需要全面系统的泛癌分析来探讨其在诊断、预后和免疫功能方面的价值。

方法

我们研究了 SIRT5 在肿瘤发生、诊断、预后、代谢途径、免疫微环境和泛癌治疗反应中的作用。此外，我们探索了影响 SIRT5 表达的化学物质，并计算了 SIRT5 与药物敏感性之间的关系。最后，通过一系列体外和体内实验分析了 SIRT5 在黑色素瘤中的作用。

结果

我们发现 SIRT5 在各种肿瘤中存在差异表达并显示出早期诊断价值，并且体细胞拷贝数改变和 DNA 甲基化导致其异常表达。SIRT5 表达与临床特征相关。此外，它与多种代谢途径呈负（正）相关，与多种重要的转移相关和免疫相关途径呈正（负）相关。SIRT5 高表达预示着各种肿瘤的不良（或良好）预后，并可能影响药物敏感性。我们还证明 SIRT5 表达与免疫调节剂相关分子、淋巴细胞亚群浸润和免疫治疗反应生物标志物显着相关。此外，我们还发现 SIRT5 在免疫治疗队列中存在差异表达。此外，我们还探索了可能影响 SIRT5 表达的各种化学物质。总之，我们证明 SIRT5 是促进黑色素瘤进展的关键致病基因。

结论

我们的研究对 SIRT5 及其调控基因进行了系统分析。SIRT5 对许多癌症具有出色的诊断和预后能力。这可能会重塑肿瘤微环境。基于 SIRT5 的癌症疗法的潜力得到强调，有助于预测免疫疗法的反应。