Omics data analysis reveals common molecular basis of small cell lung cancer and COVID-19

The impact of COVID-19 infection on individuals with small cell lung cancer (SCLC) poses a serious threat. Unfortunately, the molecular basis of this severe comorbidity has yet to be elucidated. The present study addresses this gap utilizing publicly available omics data of COVID-19 and SCLC to explore the key molecules and associated pathways involved in the convergence of these diseases. Findings revealed 402 genes, that exhibited differential expression patterns in SCLC patients and also play a pivotal role in COVID-19 pathogenesis. Subsequent functional enrichment analyses identified relevant ontologies and pathways that are significantly associated with these genes, revealing important insights into their potential biological, molecular and cellular functions. The protein-protein interaction network, constructed under four combinatorial topological assessments, highlighted SMAD3, CAV1, PIK3R1, and FN1 as the primary components to this comorbidity. Our results suggest that these components significantly regulate this cross-talk triggering the PI3K-AKT and TGF-β signaling pathways. Lastly, this study made a multi-step computational attempt and identified corylifol A and ginkgetin from natural sources that can potentially inhibit these components. Therefore, the outcomes of this study offer novel perspectives on the common molecular mechanisms underlying SCLC and COVID-19 and present future opportunities for drug development. Communicated by Ramaswamy H. Sarma

新型冠状病毒感染（COVID-19）对小细胞肺癌（small cell lung cancer, SCLC）患者的影响构成了严重威胁。遗憾的是，这种严重共病的分子机制尚未阐明。本研究利用公开可得的新型冠状病毒感染与小细胞肺癌组学数据，针对这一研究空白展开探索，以明确两种疾病交汇过程中的关键分子及相关通路。研究结果共筛选出402个基因，这些基因在小细胞肺癌患者体内呈现差异表达特征，同时在新型冠状病毒感染的发病机制中发挥关键作用。后续的功能富集分析识别出与这些基因显著相关的本体术语及通路，为解析其潜在的生物学、分子及细胞功能提供了重要见解。通过四种组合拓扑评估构建的蛋白质相互作用网络显示，SMAD3、CAV1、PIK3R1及FN1是该共病的核心组分。我们的研究结果表明，这些核心组分可显著调控该信号串扰，进而激活PI3K-AKT与转化生长因子-β（TGF-β）信号通路。最后，本研究通过多步计算分析，从天然产物中筛选出可潜在靶向抑制这些核心组分的补骨脂甲素（corylifol A）与银杏双黄酮（ginkgetin）。综上，本研究结果为解析小细胞肺癌与新型冠状病毒感染共有的分子机制提供了全新视角，同时为后续药物开发提供了潜在方向。本文由Ramaswamy H. Sarma转交刊发。