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顺铂耐药相关转录组和甲基化组整合鉴定出一种小细胞肺癌中的新型预后生物标志物。

Cisplatin resistance-related transcriptome and methylome integration identifies as a novel prognostic biomarker in small cell lung cancer.

作者信息

Zhu Qizhi, Fu Meng, Qi Jian, Xu Ziming, Wang Yongguang, Wang Zhipeng, Wang Dan, Liu Jiajia, Du Ruiping, Wei Xin, Wang Hongzhi, Nie Jinfu, Hong Bo, Xu Weiping

机构信息

Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, P.R. China.

University of Science and Technology of China, Hefei, Anhui, P.R. China.

出版信息

iScience. 2024 Jun 28;27(8):110413. doi: 10.1016/j.isci.2024.110413. eCollection 2024 Aug 16.

DOI:10.1016/j.isci.2024.110413
PMID:39108724
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11301104/
Abstract

Platinum-based chemo-resistance is the major issue for the treatment of small cell lung cancer (SCLC). The integrative analysis of multi-omics data is a reliable approach for discovering novel biomarkers associated with chemo-resistance. Here, multi-omics integrative analysis and Cox regression found that higher expression of was associated with poorer survival of SCLC patients who received chemotherapy. gene was hypomethylated and upregulated in SCLC, which was validated in the levels of promoter methylation, mRNA, and protein expression. Mechanistically, using bulk RNA-seq data, functional enrichment analysis indicated that higher expression was associated with lower immune infiltration. The analysis of single-cell RNA-seq (scRNA-seq) found that SCLC cells with expression exhibited the characteristics of stemness and EMT. In addition, the high expression and hypomethylation of were also significantly associated with poor survival in lung squamous cell carcinoma. In summary, is a potential prognostic biomarker of platinum-based chemotherapy in SCLC.

摘要

铂类化疗耐药是小细胞肺癌（SCLC）治疗中的主要问题。多组学数据的综合分析是发现与化疗耐药相关新生物标志物的可靠方法。在此，多组学综合分析和Cox回归发现，[未提及具体基因名称]的高表达与接受化疗的SCLC患者较差的生存率相关。[未提及具体基因名称]基因在SCLC中低甲基化且上调，这在启动子甲基化、mRNA和蛋白质表达水平上得到了验证。从机制上讲，使用批量RNA测序数据，功能富集分析表明，较高的[未提及具体基因名称]表达与较低的免疫浸润相关。单细胞RNA测序（scRNA-seq）分析发现，具有[未提及具体基因名称]表达的SCLC细胞表现出干性和上皮-间质转化的特征。此外，[未提及具体基因名称]的高表达和低甲基化也与肺鳞状细胞癌的不良生存显著相关。总之，[未提及具体基因名称]是SCLC中铂类化疗的潜在预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705d/11301104/f20ced393f93/gr9.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705d/11301104/8fce2f5baeb8/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705d/11301104/f20ced393f93/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705d/11301104/46a21d744da9/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705d/11301104/83b0b9bc96ba/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705d/11301104/52cc5cc6d4d7/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705d/11301104/d9ae6c738023/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705d/11301104/43c8737b48c3/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705d/11301104/7ff7cdbf5928/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705d/11301104/720c9c54197e/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705d/11301104/b9c7f2238ecd/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705d/11301104/8fce2f5baeb8/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705d/11301104/f20ced393f93/gr9.jpg

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