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Abstract：
BACKGROUND: TMPRSS2, a key molecule for SARS-CoV-2 invading human host cells, has an association with cancer. However, its association with lung cancer remains insufficiently unexplored.
METHODS: In five bulk transcriptomics datasets, one single-cell RNA sequencing (scRNA-seq) dataset and one proteomics dataset for lung adenocarcinoma (LUAD), we explored associations between TMPRSS2 expression and immune signatures, tumor progression phenotypes, genomic features, and clinical prognosis in LUAD by the bioinformatics approach. Furthermore, we performed experimental validation of the bioinformatics findings.
RESULTS: TMPRSS2 expression levels correlated negatively with the enrichment levels of both immune-stimulatory and immune-inhibitory signatures, while they correlated positively with the ratios of immune-stimulatory/immune-inhibitory signatures. It indicated that TMPRSS2 levels had a stronger negative correlation with immune-inhibitory than with immune-stimulatory signatures. TMPRSS2 downregulation correlated with increased proliferation, stemness, genomic instability, tumor progression, and worse survival in LUAD. We further validated that TMPRSS2 was downregulated with tumor progression in the LUAD cohort we collected from Jiangsu Cancer Hospital, China. In vitro and in vivo experiments verified the association of TMPRSS2 deficiency with increased tumor cell proliferation and invasion and antitumor immunity in LUAD. Moreover, in vivo experiments demonstrated that TMPRSS2-knockdown tumors were more sensitive to BMS-1, an inhibitor of PD-1/PD-L1.
CONCLUSIONS: TMPRSS2 is a tumor suppressor, while its downregulation is a positive biomarker of immunotherapy in LUAD. Our data provide a potential link between lung cancer and pneumonia caused by SARS-CoV-2 infection.
METHODS: In five bulk transcriptomics datasets, one single-cell RNA sequencing (scRNA-seq) dataset and one proteomics dataset for lung adenocarcinoma (LUAD), we explored associations between TMPRSS2 expression and immune signatures, tumor progression phenotypes, genomic features, and clinical prognosis in LUAD by the bioinformatics approach. Furthermore, we performed experimental validation of the bioinformatics findings.
RESULTS: TMPRSS2 expression levels correlated negatively with the enrichment levels of both immune-stimulatory and immune-inhibitory signatures, while they correlated positively with the ratios of immune-stimulatory/immune-inhibitory signatures. It indicated that TMPRSS2 levels had a stronger negative correlation with immune-inhibitory than with immune-stimulatory signatures. TMPRSS2 downregulation correlated with increased proliferation, stemness, genomic instability, tumor progression, and worse survival in LUAD. We further validated that TMPRSS2 was downregulated with tumor progression in the LUAD cohort we collected from Jiangsu Cancer Hospital, China. In vitro and in vivo experiments verified the association of TMPRSS2 deficiency with increased tumor cell proliferation and invasion and antitumor immunity in LUAD. Moreover, in vivo experiments demonstrated that TMPRSS2-knockdown tumors were more sensitive to BMS-1, an inhibitor of PD-1/PD-L1.
CONCLUSIONS: TMPRSS2 is a tumor suppressor, while its downregulation is a positive biomarker of immunotherapy in LUAD. Our data provide a potential link between lung cancer and pneumonia caused by SARS-CoV-2 infection.
摘要：
背景：TMPRSS2是SARS-CoV-2入侵人类宿主细胞的关键分子，与癌症有关联。然而,其与肺癌的关联仍未得到充分探索。
方法：在五个批量转录组学数据集中，一个单细胞RNA测序（scRNA-seq）数据集和一个蛋白质组学数据集用于肺腺癌（LUAD），我们探索了TMPRSS2表达与免疫特征之间的关联，肿瘤进展表型，基因组特征，并通过生物信息学方法对LUAD进行临床预后。此外，我们对生物信息学研究结果进行了实验验证.
结果：TMPRSS2表达水平与免疫刺激和免疫抑制特征的富集水平呈负相关，而它们与免疫刺激/免疫抑制特征的比率呈正相关。这表明TMPRSS2水平与免疫抑制性比与免疫刺激特征具有更强的负相关。TMPRSS2下调与增殖增加相关，stemness,基因组不稳定性，肿瘤进展，更糟糕的生存在LUAD。在江苏省肿瘤医院收集的LUAD队列中，我们进一步验证了TMPRSS2随肿瘤进展而下调。中国。体外和体内实验证实了TMPRSS2缺乏与LUAD中肿瘤细胞增殖和侵袭以及抗肿瘤免疫力增加的关系。此外，体内实验表明，TMPRSS2敲低的肿瘤对PD-1/PD-L1的抑制剂BMS-1更敏感。
结论：TMPRSS2是一种肿瘤抑制因子，而其下调是LUAD免疫治疗的阳性生物标志物。我们的数据提供了SARS-CoV-2感染引起的肺癌和肺炎之间的潜在联系。
方法：在五个批量转录组学数据集中，一个单细胞RNA测序（scRNA-seq）数据集和一个蛋白质组学数据集用于肺腺癌（LUAD），我们探索了TMPRSS2表达与免疫特征之间的关联，肿瘤进展表型，基因组特征，并通过生物信息学方法对LUAD进行临床预后。此外，我们对生物信息学研究结果进行了实验验证.
结果：TMPRSS2表达水平与免疫刺激和免疫抑制特征的富集水平呈负相关，而它们与免疫刺激/免疫抑制特征的比率呈正相关。这表明TMPRSS2水平与免疫抑制性比与免疫刺激特征具有更强的负相关。TMPRSS2下调与增殖增加相关，stemness,基因组不稳定性，肿瘤进展，更糟糕的生存在LUAD。在江苏省肿瘤医院收集的LUAD队列中，我们进一步验证了TMPRSS2随肿瘤进展而下调。中国。体外和体内实验证实了TMPRSS2缺乏与LUAD中肿瘤细胞增殖和侵袭以及抗肿瘤免疫力增加的关系。此外，体内实验表明，TMPRSS2敲低的肿瘤对PD-1/PD-L1的抑制剂BMS-1更敏感。
结论：TMPRSS2是一种肿瘤抑制因子，而其下调是LUAD免疫治疗的阳性生物标志物。我们的数据提供了SARS-CoV-2感染引起的肺癌和肺炎之间的潜在联系。
