经过几多波折，我们用血浆转录组来发现小肺化疗耐药相关的生物学标记物（gene signatures）工作终于在Front. Immunol.上见刊了。 由于小肺患者普遍不进行手术治疗，血浆转录组是一个低成本的耐药监测方式。在这篇文章里，我们和云南省肿瘤医院的杨润祥主任和杨芳医生合作，采用了我们团队之前发展的stSVM(2012 PloS One； 2013 Bioinformatics）、核心网络分析（2022 NanoToday，2023 JIPB）和别人的伪单细胞分析（Xcell）对17个小肺患者治疗前后的血浆转录组进行了系统分析，找到和原发耐药（primary resistance）相关的几个基因 PRICKLE3, TNFSFI0, ACSLl and EP300。血浆的东西太混杂，如何从里面找到有效的biomarker来监控肿瘤治疗过程中的分子变异是个非常有挑战性的工作。 我在这里做了一个小尝试，希望能给这个领域的biomaker 发现提供一些方法的路线建议。在这篇文章里，金花也完成了从wet-lab到dry-lab的升级。

这个工作是我2015年小肺Nature基因组和转录组系统分析文章（Comprehensive genomic profiles of small cell lung cancer）的后第一篇小肺相关的工作。感慨颇多，2016年底回国后辗转多地，没能耐住性子做了很多辅助性“无用”的数据分析，和许多“外行”项目数据分析，却把自己最擅长的 machine learning in computational biology 和 computational cancer genome 工作荒废了不少。

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Integrative analysis of blood transcriptome profiles in small-cell lung cancer patients for identification of novel chemotherapy resistance-related biomarkers

Introduction: Chemoresistance constitutes a prevalent factor that significantly impacts the survival of patients undergoing treatment for small-cell lung cancer (SCLC). Chemotherapy resistance in SCLC patients is generally classified as primary or acquired resistance, each governed by distinct mechanisms that remain inadequately researched.

Methods: In this study, we performed transcriptome screening of peripheral blood plasma obtained from 17 patients before and after receiving combined etoposide and platinum treatment. We first estimated 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.

Results: Our analysis showed a significant increase in class-switched memory B cell scores acrossboth chemotherapy resistance patterns, indicating their potential crucial role in mediating resistance. Moreover, network analysis identified PRICKLE3, TNFSFI0, ACSLl and EP300 as potential contributors to primary resistance, with SNWl, SENP2 and SMNDCl emerging as significant factors in acquired resistance, providing valuable insights into chemotherapy resistance in SCLC.

Discussion: These findings offer valuable insights for understanding chemotherapy resistance and related gene signatures in SCLC, which could help further biological validation studies.