Squamous cell lung carcinoma (SqCLC) is associated with high mortality and limited treatment options. Identification of therapeutic targets and prognostic biomarkers is still lacking. This research aims to analyze the transcriptomic profile of SqCLC samples and identify the key genes associated with tumorigenesis, overall survival (OS), and a profile of the tumor-infiltrating immune cells. Differential gene expression analysis, pathway enrichment analysis, and Gene Ontology analysis on RNA-seq data obtained from FFPE tumor samples (N= 23) and healthy tissues (N= 3) were performed (experimental cohort). Validation of the results was conducted on publicly available gene expression data using TCGA LUSC (N= 225) and GTEx healthy donors’ cohorts (N= 288). We identified 1133 upregulated and 644 downregulated genes, common for both cohorts. The most prominent upregulated genes were involved in cell cycle and proliferation regulation pathways (MAGEA9B, MAGED4, KRT, MMT11/13), while downregulated genes predominately belonged to immune-related pathways (DEFA1B, DEFA1, DEFA3). Results of the survival analysis, conducted on the validation cohort and commonly deregulated genes, indicated that overexpression of HOXC4 (p< 0.001), LLGL1 (p= 0.0015), and SLC4A3 (p= 0.0034) is associated with worse OS in early-stage SqCLC patients. In contrast, overexpression of GSTZ1 (p= 0.0029) and LILRA5 (p= 0.0086) was protective, i.e., associated with better OS. By applying a single-sample gene-set enrichment analysis (ssGSEA), we identified four distinct immune subtypes. Immune cell distribution suggests that the memory T cells (central and effector) and follicular helper T cells could serve as important stratification parameters.
肺鳞状细胞癌（SqCLC）具有高死亡率且治疗选择有限，目前仍缺乏有效的治疗靶点与预后生物标志物。本研究旨在分析SqCLC样本的转录组特征，识别与肿瘤发生、总生存期（OS）及肿瘤浸润免疫细胞谱相关的关键基因。研究对来自福尔马林固定石蜡包埋（FFPE）肿瘤样本（N=23）与健康组织（N=3）的RNA-seq数据进行了差异基因表达分析、通路富集分析和基因本体分析（实验队列）。结果在公开基因表达数据集TCGA LUSC（N=225）和GTEx健康供体队列（N=288）中进行了验证。我们在两个队列中共同鉴定出1133个上调基因和644个下调基因。其中显著上调的基因主要参与细胞周期与增殖调控通路（如MAGEA9B、MAGED4、KRT、MMT11/13），而下调基因则主要属于免疫相关通路（如DEFA1B、DEFA1、DEFA3）。基于验证队列及共同失调基因的生存分析结果显示，HOXC4（p<0.001）、LLGL1（p=0.0015）和SLC4A3（p=0.0034）的过表达与早期SqCLC患者较差的OS相关；相反，GSTZ1（p=0.0029）和LILRA5（p=0.0086）的过表达则具有保护作用，即与更好的OS相关。通过单样本基因集富集分析（ssGSEA），我们识别出四种不同的免疫亚型。免疫细胞分布特征提示，记忆T细胞（中央型与效应型）及滤泡辅助T细胞可作为重要的分层参数。
Transcriptomic Profiling for Prognostic Biomarkers in Early-Stage Squamous Cell Lung Cancer (SqCLC)
肿瘤(癌症)患者之家