{"title":"鉴定中国人群中与胃癌存活率相关的 KCNQ 家族基因的常见遗传变异。","authors":"Yuetong Chen, Chen Li, Yi Shi, Jiali Dai, Yixuan Meng, Shuwei Li, Cuiju Tang, Dongying Gu, Jinfei Chen","doi":"10.7555/JBR.38.20240040","DOIUrl":null,"url":null,"abstract":"<p><p>The <i>KCNQ</i> family of genes ( <i>KCNQ1</i>- <i>KCNQ5</i>), encoding voltage-gated K <sup>+</sup> (Kv) channels, have been demonstrated to play potential pathophysiological roles in cancers. However, the associations between genetic variants located in <i>KCNQ</i> family genes and gastric cancer survival remain unclear. In this study, a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in <i>KCNQ</i> family genes associated with overall survival (OS). Based on the survival evaluation of all five <i>KCNQ</i> family genes, <i>KCNQ1</i> was selected for subsequent genetic analysis. In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants, we found that <i>KCNQ1</i> rs10832417G>T was associated with an increased OS in gastric cancer patients (adjusted hazards ratio [HR] = 0.84, 95% confidence interval [CI]: 0.72-0.98, <i>P</i> = 0.023). Subsequently, a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants. The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure. Furthermore, we observed that gastric cancer patients with downregulated <i>KCNQ1</i> expression had a poorer survival across multiple public datasets. The findings of the present study indicate that <i>KCNQ1</i> rs10832417 may serve as an independent prognostic predictor of gastric cancer, providing novel insights into the progression and survival of the disease.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"76-86"},"PeriodicalIF":2.2000,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification of common genetic variants in <i>KCNQ</i> family genes associated with gastric cancer survival in a Chinese population.\",\"authors\":\"Yuetong Chen, Chen Li, Yi Shi, Jiali Dai, Yixuan Meng, Shuwei Li, Cuiju Tang, Dongying Gu, Jinfei Chen\",\"doi\":\"10.7555/JBR.38.20240040\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The <i>KCNQ</i> family of genes ( <i>KCNQ1</i>- <i>KCNQ5</i>), encoding voltage-gated K <sup>+</sup> (Kv) channels, have been demonstrated to play potential pathophysiological roles in cancers. However, the associations between genetic variants located in <i>KCNQ</i> family genes and gastric cancer survival remain unclear. In this study, a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in <i>KCNQ</i> family genes associated with overall survival (OS). Based on the survival evaluation of all five <i>KCNQ</i> family genes, <i>KCNQ1</i> was selected for subsequent genetic analysis. In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants, we found that <i>KCNQ1</i> rs10832417G>T was associated with an increased OS in gastric cancer patients (adjusted hazards ratio [HR] = 0.84, 95% confidence interval [CI]: 0.72-0.98, <i>P</i> = 0.023). Subsequently, a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants. The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure. Furthermore, we observed that gastric cancer patients with downregulated <i>KCNQ1</i> expression had a poorer survival across multiple public datasets. The findings of the present study indicate that <i>KCNQ1</i> rs10832417 may serve as an independent prognostic predictor of gastric cancer, providing novel insights into the progression and survival of the disease.</p>\",\"PeriodicalId\":15061,\"journal\":{\"name\":\"Journal of Biomedical Research\",\"volume\":\" \",\"pages\":\"76-86\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-05-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biomedical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7555/JBR.38.20240040\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biomedical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7555/JBR.38.20240040","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
摘要
编码电压门控 K +(Kv)通道的 KCNQ 家族基因(KCNQ1-5)被发现在癌症中具有潜在的病理生理作用。然而,KCNQ家族基因中的遗传变异与胃癌生存之间的关系仍不清楚。研究人员加入了一个由1,135名中国胃癌患者组成的大规模队列,以确定KCNQ家族基因中与总生存期(OS)相关的遗传变异。根据对所有五个成员的生存评估,选择 KCNQ1 进行后续遗传分析。采用 Cox 回归模型和逐步 Cox 回归模型评估与生存相关的遗传变异。我们发现,KCNQ1 rs10832417与胃癌患者OS增加相关(调整后危险比(HR)= 0.84,95%置信区间(CI):0.72-0.98,P = 0.023)。随后,我们生成了一个提名图,以支持 rs10832417 变体的预后能力和临床转化。据预测,rs10832417 T 等位基因会增加二级结构的最小自由能(MFE)。此外,我们在多个公共数据集中观察到,KCNQ1下调的胃癌患者生存率较低。本研究发现,KCNQ1 rs10832417可作为胃癌的独立预后预测因子,为胃癌的进展和生存提供了新的见解。
Identification of common genetic variants in KCNQ family genes associated with gastric cancer survival in a Chinese population.
The KCNQ family of genes ( KCNQ1- KCNQ5), encoding voltage-gated K + (Kv) channels, have been demonstrated to play potential pathophysiological roles in cancers. However, the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear. In this study, a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival (OS). Based on the survival evaluation of all five KCNQ family genes, KCNQ1 was selected for subsequent genetic analysis. In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants, we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients (adjusted hazards ratio [HR] = 0.84, 95% confidence interval [CI]: 0.72-0.98, P = 0.023). Subsequently, a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants. The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure. Furthermore, we observed that gastric cancer patients with downregulated KCNQ1 expression had a poorer survival across multiple public datasets. The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer, providing novel insights into the progression and survival of the disease.