Decreased TMPRSS2 expression by SARS-CoV-2 predicts the poor prognosis of lung cancer patients through metabolic pathways and immune infiltration

Liu, Xiaopeng; Liu, Bing; Shang, Yanan; Cao, Pengxiu; Hou, Jiajie; Chen, Fei; Zhang, Bo; Fan, Yumei; Tan, Karsoon

doi:10.18632/aging.203823

Cited by 5 publications

(3 citation statements)

References 49 publications

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“…Because SARS-CoV infection downregulates TMPRSS2 expression in cultured cells [ 22 ], we investigated the changes in TMPRSS2 expression in COVID-19-infected lungs. By analyzing the single-cell RNA-sequencing dataset (GSE171524) of COVID-19-infected lungs and control lungs [ 23 ], the expression levels of TMPRSS2 in COVID-19-infected lungs were significantly reduced compared to the control lungs ( Figure 7 A).…”

Section: Resultsmentioning

confidence: 99%

Impact of TMPRSS2 Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2

Tan

Liu

et al. 2022

Molecules

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As a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyses for the TMPRSS2 gene in pan-cancers as well as in COVID-19-infected lung tissues. The results indicate that TMPRSS2 expression was highest in prostate cancer. A high expression of TMPRSS2 was significantly associated with a short overall survival in breast invasive carcinoma (BRCA), sarcoma (SARC), and uveal melanoma (UVM), while a low expression of TMPRSS2 was significantly associated with a short overall survival in lung adenocarcinoma (LUAD), demonstrating TMPRSS2 roles in cancer patient susceptibility and severity. Additionally, TMPRSS2 expression in COVID-19-infected lung tissues was significantly reduced compared to healthy lung tissues, indicating that a low TMPRSS2 expression may result in COVID-19 severity and death. Importantly, TMPRSS2 mutation frequency was significantly higher in prostate adenocarcinoma (PRAD), and the mutant TMPRSS2 pan-cancer group was significantly associated with long overall, progression-free, disease-specific, and disease-free survival rates compared to the wild-type (WT) TMPRSS2 pan-cancer group, demonstrating loss of functional roles due to mutation. Cancer cell lines were treated with small molecules, including cordycepin (CD), adenosine (AD), thymoquinone (TQ), and TQFL12, to mediate TMPRSS2 expression. Notably, CD, AD, TQ, and TQFL12 inhibited TMPRSS2 expression in cancer cell lines, including the PC3 prostate cancer cell line, implying a therapeutic role for preventing COVID-19 in cancer patients. Together, these findings are the first to demonstrate that small molecules, such as CD, AD, TQ, and TQFL12, inhibit TMPRSS2 expression, providing novel therapeutic strategies for preventing COVID-19 and cancers.

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Section: Resultsmentioning

confidence: 99%

Impact of TMPRSS2 Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2

Tan

Liu

et al. 2022

Molecules

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“…Immunohistochemical (IHC) staining results were directly obtained from the HPA (Human Protein Atlas) database ( https://www.proteinatlas.org/ ) as described previously [ 36 , 87 ]. The protein levels of PRGs in normal liver tissues and HCC tissues were compared through IHC staining.…”

Section: Methodsmentioning

confidence: 99%

A novel risk score model based on pyroptosis-related genes for predicting survival and immunogenic landscape in hepatocellular carcinoma

Wang

Zhang

Shang

et al. 2023

Aging

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Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer worldwide, with high incidence and mortality. Pyroptosis, a form of inflammatory-regulated cell death, is closely associated with oncogenesis. Methods: Expression profiles of HCC were downloaded from the TCGA database and validated using the ICGC and GEO databases. Consensus clustering analysis was used to determine distinct clusters. The pyroptosis-related genes (PRGs) included in the pyroptosis-related signature were selected by univariate Cox regression and LASSO regression analysis. Kaplan-Meier and receiver operating characteristic (ROC) analyses were performed to estimate the prognostic potential of the model. The characteristics of infiltration of immune cells between different groups of HCC were explored. Results: Two independent clusters were identified according to PRG expression. Cluster 2 showed upregulated expression, poor prognosis, increased immune cell infiltration and worse immunotherapy response than cluster 1. A prognostic risk signature consisting of five genes (GSDME, NOD1, PLCG1, NLRP6 and NLRC4) was identified. In the high-risk score group, HCC patients showed decreased survival rates. In particular, multiple clinicopathological characteristics and immune cell infiltration were significantly associated with the risk score. Notably, the 5 PRGs in the risk score have been implicated in carcinogenesis, immunological pathways and drug sensitivity. Conclusions: A prognostic signature comprising five PRGs can be used as a potential prognostic factor for HCC. The PRG-related signature provides an in-depth understanding of the association between pyroptosis and chemotherapy or immunotherapy for HCC patients.

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“…For example, the TMPRSS2 gene expression was significantly reduced in patients with LUAD as compared with healthy patients, although the ACE2 expression was higher in the former group ( 84 – 86 ). Moreover, the TMPRSS2 gene expression was significantly reduced in patients with LUSC as compared with healthy patients, although the ACE2 expression was high in the patients with both LUAD and LUSC ( 87 ).…”

Section: Biological Effects Of Sars-cov-2 On Lung Cancermentioning

confidence: 95%

Biological effects of COVID-19 on lung cancer: Can we drive our decisions

et al. 2022

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COVID-19 infection caused by SARS-CoV-2 is considered catastrophic because it affects multiple organs, particularly those of the respiratory tract. Although the consequences of this infection are not fully clear, it causes damage to the lungs, the cardiovascular and nervous systems, and other organs, subsequently inducing organ failure. In particular, the effects of SARS-CoV-2-induced inflammation on cancer cells and the tumor microenvironment need to be investigated. COVID-19 may alter the tumor microenvironment, promoting cancer cell proliferation and dormant cancer cell (DCC) reawakening. DCCs reawakened upon infection with SARS-CoV-2 can populate the premetastatic niche in the lungs and other organs, leading to tumor dissemination. DCC reawakening and consequent neutrophil and monocyte/macrophage activation with an uncontrolled cascade of pro-inflammatory cytokines are the most severe clinical effects of COVID-19. Moreover, neutrophil extracellular traps have been demonstrated to activate the dissemination of premetastatic cells into the lungs. Further studies are warranted to better define the roles of COVID-19 in inflammation as well as in tumor development and tumor cell metastasis; the results of these studies will aid in the development of further targeted therapies, both for cancer prevention and the treatment of patients with COVID-19.

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Decreased TMPRSS2 expression by SARS-CoV-2 predicts the poor prognosis of lung cancer patients through metabolic pathways and immune infiltration

Cited by 5 publications

References 49 publications

Impact of TMPRSS2 Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2

Impact of TMPRSS2 Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2

A novel risk score model based on pyroptosis-related genes for predicting survival and immunogenic landscape in hepatocellular carcinoma

Biological effects of COVID-19 on lung cancer: Can we drive our decisions

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