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线粒体相关基因SLC25A32作为一种新型的预后和免疫治疗生物标志物：从泛癌多组学分析到乳腺癌验证

Mitochondria-Associated Gene SLC25A32 as a Novel Prognostic and Immunotherapy Biomarker: From Pan-Cancer Multiomics Analysis to Breast Cancer Validation.

作者信息

Zuo Shiqi, He Siyuan, Zhu Zhiqin, Zhang Yingying, Hou Yanjie, Wu Ziqing, Tang Yao

机构信息

Department of Pathology, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, Guangdong 510315, China.

Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Southern Medical University, Guangzhou 510515, Guangdong, China.

出版信息

Anal Cell Pathol (Amst). 2024 Apr 29;2024:1373659. doi: 10.1155/2024/1373659. eCollection 2024.

DOI:10.1155/2024/1373659
PMID:39624160
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11611429/
Abstract

BACKGROUND

Mutations in SLC25A32 in humans cause late-onset exercise intolerance, which is associated with various neurological and metabolic diseases. However, its specific mechanism of action in tumour development is poorly understood owing to the lack of multiomics integrated analysis of SLC25A32 in pan-cancer.

METHODS

We used various analytical tools to comprehensively investigate the transcription, protein level, and promoter methylation of SLC25A32. Furthermore, the GSCA and cBioPortal databases were used to evaluate the inheritance impact and epigenetic alterations of SLC25A32 in pan-cancer. SLC25A32 expression and the prognostic significance of copy number alterations in multiple cancers were compared using the UCSCXenaShiny and GEPIA2.0 platforms, and its specific function in breast cancer was experimentally verified.

RESULTS

SLC25A32 is abnormally expressed at the transcriptional and protein levels in most cancer types, with aberrant DNA promoter methylation and significant gene amplification in most tumours. SLC25A32 is significantly associated with the survival prognosis of some cancers, immune infiltrating cells, tumour stemness, and immune-related markers. SLC25A32 knockdown decreased breast tumour cell proliferation, invasion, and metastasis.

CONCLUSIONS

This study aimed to reveal SLC25A32 as a novel prognostic biomarker for pan-cancer prediction and immunotherapy efficacy and specifically describes its underlying mechanism of action in breast cancer. SLC25A32 is widely differentially expressed in pan-cancer with prognostic significance and is correlated with immune infiltration. Additionally, it can affect breast cancer occurrence and development.

摘要

背景

人类SLC25A32基因突变会导致迟发性运动不耐受，这与多种神经和代谢疾病有关。然而，由于缺乏对泛癌中SLC25A32的多组学综合分析，其在肿瘤发生发展中的具体作用机制尚不清楚。

方法

我们使用了各种分析工具，全面研究SLC25A32的转录、蛋白质水平和启动子甲基化。此外，利用GSCA和cBioPortal数据库评估SLC25A32在泛癌中的遗传影响和表观遗传改变。使用UCSCXenaShiny和GEPIA2.0平台比较了SLC25A32在多种癌症中的表达以及拷贝数改变的预后意义，并通过实验验证了其在乳腺癌中的具体功能。

结果

SLC25A32在大多数癌症类型的转录和蛋白质水平上异常表达，在大多数肿瘤中存在异常的DNA启动子甲基化和显著的基因扩增。SLC25A32与某些癌症的生存预后、免疫浸润细胞、肿瘤干性和免疫相关标志物显著相关。敲低SLC25A32可降低乳腺肿瘤细胞的增殖、侵袭和转移能力。

结论

本研究旨在揭示SLC25A32作为一种新型的预后生物标志物，用于泛癌预测和免疫治疗疗效评估，并具体描述其在乳腺癌中的潜在作用机制。SLC25A32在泛癌中广泛差异表达，具有预后意义，且与免疫浸润相关。此外，它还可影响乳腺癌的发生发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f08/11611429/28c876282885/ACP2024-1373659.010.jpg
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