Evaluation of the association between sex-linked genes and treatment response in lung cancer

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology Pub Date : 2025-09-20 DOI:10.1016/j.radonc.2025.111159

A Kinsella , A Prina-Mello , L Marignol

{"title":"Evaluation of the association between sex-linked genes and treatment response in lung cancer","authors":"A Kinsella , A Prina-Mello , L Marignol","doi":"10.1016/j.radonc.2025.111159","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and Purpose</h3><div>The impact of biological sex on treatment response and prognosis in lung cancer remains poorly understood. This study investigates the relationship between sex-linked genes, DNA repair, senescence, and survival in male and female patients with lung cancer.</div></div><div><h3>Materials and Methods</h3><div>Whole-genome mRNA expression data from The Cancer Genome Atlas (TCGA) PanCancer Atlas for lung adenocarcinoma (LUAD) were analyzed (N = 275 female, N = 239 male). Curated lists of 874 X-linked, 57 Y-linked, and 314 DNA damage response (DDR) genes were obtained from UniProt and HUGO. Additionally, 279 senescence genes were sourced from <span><span>Senescence.info</span><svg><path></path></svg></span>. Overall survival (OS) was assessed using Kaplan-Meier analysis. Correlation analyses between sex-linked and DDR/senescence genes used Spearman’s rank correlation. Based on their strong association with DDR genes and OS in patient tumours, two top-ranked X-linked genes, <em>CENPI</em> and <em>ERCC6L</em>, were further evaluated <em>in vitro</em> in male (A549) and female (H1975) lung adenocarcinoma cells after radiation or fisetin treatment.</div></div><div><h3>Results</h3><div>Of 44 Y-linked genes evaluated, 11 were differentially expressed; <em>PRKY</em> was significantly associated with OS. In tumours, 287 (male) and 314 (female) X-linked genes were altered, with strong correlations to DDR genes. Low <em>ERCC6L</em> expression was linked to increased OS in males treated with radiation (p = 0.036, HR = 3.1). Radiation and fisetin treatment modified <em>CENPI</em> and <em>ERCC6L</em> expression in a sex-specific manner.</div></div><div><h3>Conclusion</h3><div>Sex-linked gene expression in lung tumours influences DDR and senescence pathways, correlating with survival outcomes. These findings highlight the importance of sex-specific analysis in lung cancer research and treatment.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"212 ","pages":"Article 111159"},"PeriodicalIF":5.3000,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Radiotherapy and Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0167814025051631","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background and Purpose

The impact of biological sex on treatment response and prognosis in lung cancer remains poorly understood. This study investigates the relationship between sex-linked genes, DNA repair, senescence, and survival in male and female patients with lung cancer.

Materials and Methods

Whole-genome mRNA expression data from The Cancer Genome Atlas (TCGA) PanCancer Atlas for lung adenocarcinoma (LUAD) were analyzed (N = 275 female, N = 239 male). Curated lists of 874 X-linked, 57 Y-linked, and 314 DNA damage response (DDR) genes were obtained from UniProt and HUGO. Additionally, 279 senescence genes were sourced from Senescence.info. Overall survival (OS) was assessed using Kaplan-Meier analysis. Correlation analyses between sex-linked and DDR/senescence genes used Spearman’s rank correlation. Based on their strong association with DDR genes and OS in patient tumours, two top-ranked X-linked genes, CENPI and ERCC6L, were further evaluated in vitro in male (A549) and female (H1975) lung adenocarcinoma cells after radiation or fisetin treatment.

Results

Of 44 Y-linked genes evaluated, 11 were differentially expressed; PRKY was significantly associated with OS. In tumours, 287 (male) and 314 (female) X-linked genes were altered, with strong correlations to DDR genes. Low ERCC6L expression was linked to increased OS in males treated with radiation (p = 0.036, HR = 3.1). Radiation and fisetin treatment modified CENPI and ERCC6L expression in a sex-specific manner.

Conclusion

Sex-linked gene expression in lung tumours influences DDR and senescence pathways, correlating with survival outcomes. These findings highlight the importance of sex-specific analysis in lung cancer research and treatment.

查看原文本刊更多论文

肺癌患者性别连锁基因与治疗反应相关性的评估。

背景与目的：生物学性别对肺癌治疗反应和预后的影响尚不清楚。本研究探讨性别连锁基因、DNA修复、衰老和男女肺癌患者生存之间的关系。材料和方法：分析来自Cancer Genome Atlas （TCGA）胰腺癌Atlas for lung adenocaroma （LUAD）的全基因组mRNA表达数据（N = 275名女性，N = 239名男性）。从UniProt和HUGO获得了874个x连锁、57个y连锁和314个DNA损伤反应（DDR）基因的筛选列表。此外，279个衰老基因来自senesence .info。采用Kaplan-Meier分析评估总生存期（OS）。利用Spearman秩相关分析性别连锁基因与DDR/衰老基因的相关性。基于它们与肿瘤患者DDR基因和OS的强相关性，我们进一步在放射或非西汀治疗后的男性（A549）和女性（H1975）肺腺癌细胞中对两个排名靠前的X-linked基因CENPI和ERCC6L进行了体外评估。结果：44个y连锁基因中，有11个差异表达；PRKY与OS显著相关。在肿瘤中，287个（男性）和314个（女性）x连锁基因被改变，与DDR基因有很强的相关性。低ERCC6L表达与放射治疗的男性OS增加有关（p = 0.036,HR = 3.1）。放疗和非瑟酮治疗以性别特异性的方式改变了CENPI和ERCC6L的表达。结论：肺肿瘤性别连锁基因表达影响DDR和衰老途径，与生存结果相关。这些发现强调了性别特异性分析在肺癌研究和治疗中的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Radiotherapy and Oncology 医学-核医学

CiteScore

10.30

自引率

10.50%

发文量

2445

审稿时长

45 days

期刊介绍： Radiotherapy and Oncology publishes papers describing original research as well as review articles. It covers areas of interest relating to radiation oncology. This includes: clinical radiotherapy, combined modality treatment, translational studies, epidemiological outcomes, imaging, dosimetry, and radiation therapy planning, experimental work in radiobiology, chemobiology, hyperthermia and tumour biology, as well as data science in radiation oncology and physics aspects relevant to oncology.Papers on more general aspects of interest to the radiation oncologist including chemotherapy, surgery and immunology are also published.