对小细胞肺癌患者血液转录组谱进行综合分析,以鉴定新型化疗耐药相关生物标志物。
Integrative analysis of blood transcriptome profiles in small-cell lung cancer patients for identification of novel chemotherapy resistance-related biomarkers.
发表日期:2024
作者:
Fang Yang, Jinhua Fan, Runxiang Yang, Yupeng Cun
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
化疗耐药是显着影响接受小细胞肺癌(SCLC)治疗的患者生存的普遍因素。 SCLC 患者的化疗耐药通常分为原发性或获得性耐药,每种耐药机制均由不同的机制控制,但这些机制尚未得到充分研究。在这项研究中,我们对 17 名接受依托泊苷和铂类联合治疗前后的患者的外周血浆进行了转录组筛查。我们首先使用 xCell 和 ESTIMATE 验证了伪单细胞分析,并鉴定了差异表达基因 (DEG),然后进行网络分析以发现参与化疗耐药性的关键中心基因。我们的分析显示类别转换记忆 B 细胞评分显着增加跨越两种化疗耐药模式,表明它们在介导耐药性中具有潜在的关键作用。此外,网络分析确定 PRICKLE3、TNFSFI0、ACSL1 和 EP300 是原发性耐药的潜在贡献者,而 SNW1、SENP2 和 SMNDCl 是获得性耐药中新兴的重要因素,为 SCLC 化疗耐药性提供了有价值的见解。这些发现为了解化疗耐药性和耐药性提供了宝贵的见解。 SCLC 中的相关基因特征,有助于进一步的生物学验证研究。版权所有 © 2024 Yang、Fan、Yang 和 Cun。
Chemoresistance constitutes a prevalent factor that significantly impacts thesurvival of patients undergoing treatment for smal-cell lung cancer (SCLC). Chemotherapy resistance in SCLC patients is generally classified as primary or acquired resistance, each governedby distinct mechanisms that remain inadequately researched.In this study, we performed transcriptome screening of peripheral blood plasma obtainedfrom 17 patients before and after receiving combined etoposide and platinum treatment. We firs testimated pseudo-single-cell analysis using xCell and ESTIMATE and identified differentially expressed genes (DEGs), then performed network analysis to discover key hub genes involved in chemotherapy resistance.Our analysis showed a significant increase in class-switched memory B cell scores acrossboth chemotherapy resistance patterns, indicating their potential crucial role in mediatingresistance. Moreover, network analysis identifed PRICKLE3, TNFSFI0, ACSLl and EP300 as potential contributors to primary resistance, with SNWl, SENP2 and SMNDCl emerging assignificant factors in acquired resistance, providing valuable insights into chemotherapy resistancein SCLC.These findings offer valuable insights for understanding chemotherapy resistance and related gene signatures in SCLC, which could help further biological validation studies.Copyright © 2024 Yang, Fan, Yang and Cun.