Colorectal Cancer that Highly Express Both ACE2 and TMPRSS2, Suggesting Severe Symptoms to SARS-CoV-2 Infection

Wang, Huai; Yang, Jiankang

doi:10.3389/pore.2021.612969

Cited by 6 publications

(4 citation statements)

References 10 publications

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“…However, studies concerning the implications of TMPRSS2 expression in patients with CRC remain conflicting. Wang et al showed that TMPRSS2 was highly expressed in CRC which suggests severe symptoms of SARS-CoV-2 Infection ( 27 ). We thus applied multiomics tools to explore the role of TMPRSS2 expression in CRC and evaluated the correlation between TMPRSS2 expression and immunotherapy response to glean new insights into the impact of COVID-19 infection on CRC.…”

Section: Discussionmentioning

confidence: 99%

Transmembrane serine protease 2, a SARS-CoV-2 internalization protease, correlates with clinical outcome, molecular features, and immunotherapy response in colorectal cancer

Zhu,

Wu,

Shelat

et al. 2023

J Gastrointest Oncol

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Background Transmembrane serine protease 2 (TMPRSS2) mediates the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells. The relevant research indicates the intestine to be a target of SARS-CoV-2 infection, and thus we aimed to investigate the correlation between TMPRSS2 expression and the prognosis, molecular features, and immunotherapy response in patients with colorectal cancer (CRC). Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used in this study and a total of 1,385 patients were identified. The CIBERSORT algorithms were used to evaluate the relative infiltration levels of immune cell types in the tumor microenvironment (TME). The correlation between TMPRSS2 expression and immunotherapy response rate was assessed in another 2 independent cohorts. Results TMPRSS2 expression was significantly downregulated in cancer tissue compared to the adjacent normal tissue, and patients with CRC with lower TMPRSS2 expression showed notably poorer prognosis. Functional enrichment analysis found that low TMPRSS2 expression was significantly associated with cancer metastasis-related pathways. Further analysis based on the miRWalk tool and JASPAR database identified a list of microRNAs (miRNAs) and transcriptional factors targeting TMPRSS2 . Distinct differences in immune cell infiltration and tumor purity reflected by estimate and mutant-allele tumor heterogeneity score were observed between patients with low and high TMPRSS2 expression levels. Interestingly, patients with a low TMPRSS2 expression level showed a higher response rate to immunotherapy. Conclusions CRC cells may be more resistant to SARS-CoV-2 infection due to the decreased expression of TMPRSS2 , which could be a newly identified biomarker for prognosis and immunotherapy response prediction in patients with CRC.

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Section: Discussionmentioning

confidence: 99%

Transmembrane serine protease 2, a SARS-CoV-2 internalization protease, correlates with clinical outcome, molecular features, and immunotherapy response in colorectal cancer

Zhu,

Wu,

Shelat

et al. 2023

J Gastrointest Oncol

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“…The Chinese Drug Administration approved 3 proprietary Chinese medicines, including Lianhuaqingwen granules, for the treatment of COVID-19 ( Ni et al, 2020 ). ACE2 and TMPRSS2 proteins mediate SARS-CoV-2 virus invasion into host cells, and among all cancers, only patients with COAD and rectal adenocarcinoma showed upregulated expression of ACE2 and TMPRSS2 proteins in vivo , so patients with COAD and rectal adenocarcinoma may be more susceptible to contracting SARS-CoV-2 ( Hoang et al, 2021 ; Wang and Yang, 2021 ). Furthermore, it was found that cancer patients infected with SARS-CoV-2 virus tend to have a poorer survival prognosis than healthy patients infected with SARS-CoV-2 virus due to the suppression of the systemic immune system caused by the effects of tumor and anti-cancer treatment ( Liang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Potential therapeutic strategies for quercetin targeting critical pathological mechanisms associated with colon adenocarcinoma and COVID-19

Liang²,

Yu³

et al. 2022

Front. Pharmacol.

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Patients with colon adenocarcinoma (COAD) are at a higher probability of infection with COVID-19 than healthy individuals. However, there is no globally accepted treatment protocol for patients with COAD/COVID-19. Quercetin has been found to have significant antitumor, antiviral and anti-inflammatory effects in several studies. Therefore, this study sought to evaluate the potential of quercetin as the agent for COAD/COVID-19 and to explore its mechanisms. We used bioinformatics algorithms to obtain COAD/COVID-19-related genes (CCRG) from COAD-related transcriptome data and COVID-related transcriptome sequencing data, and used these genes to construct a COAD prognostic model. We intersected the CCRG with the therapeutic target genes of quercetin and obtained a total of 105 genes (potential target genes of quercetin for the treatment of COAD/COVID-19). By constructing a protein-protein interaction (PPI) network, we ascertained FOS, NFKB1, NFKB1A, JUNB, and JUN as possible core target genes of quercetin for the treatment of COAD/COVID-19. Bioinformatic analysis of these 105 genes revealed that the mechanisms for quercetin the treatment of COAD/COVID-19 may be associated with oxidative stress, apoptosis, anti-inflammatory, immune, anti-viral and multiple pathways containing IL-17, TNF, HIF-1. In this study, we constructed a prognostic model of COAD/COVID19 patients by using CCRG and elucidated for the first time the potential target genes and molecular mechanisms of quercetin for the treatment of COAD/COVID-19, which may benefit the clinical treatment of COAD/COVID-19 patients. However, no clinical trials have yet been conducted to further validate the findings, but this will be the future direction of our research.

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“…ACE2 expression is also raised in renal cancer and gastrointestinal cancer [52]. It is noteworthy that ACE2 and TMPRSS2 are expressed at high levels on tumor and normal colorectal epithelial tissues and that patients with colorectal cancer and COVID-19 are more likely to have lymphopenia, higher respiratory rate, and high hypersensitive C-reactive protein levels than matched patients with COVID-19 but without cancer [53,54]. Finally, landscape profiling analyses on the expression level of ACE2 in pan-cancers have revealed that the risk for development of SARS-CoV-2 infection was coupled with the expression level of ACE2 [36].…”

Section: Cancermentioning

confidence: 99%

ACE2, the Counter-Regulatory Renin–Angiotensin System Axis and COVID-19 Severity

Triposkiadis

Xanthopoulos

Giamouzis

et al. 2021

JCM

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Angiotensin (ANG)-converting enzyme (ACE2) is an entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). ACE2 also contributes to a deviation of the lung renin–angiotensin system (RAS) towards its counter-regulatory axis, thus transforming harmful ANG II to protective ANG (1–7). Based on this purported ACE2 double function, it has been put forward that the benefit from ACE2 upregulation with renin–angiotensin–aldosterone system inhibitors (RAASi) counterbalances COVID-19 risks due to counter-regulatory RAS axis amplification. In this manuscript we discuss the relationship between ACE2 expression and function in the lungs and other organs and COVID-19 severity. Recent data suggested that the involvement of ACE2 in the lung counter-regulatory RAS axis is limited. In this setting, an augmentation of ACE2 expression and/or a dissociation of ACE2 from the ANG (1–7)/Mas pathways that leaves unopposed the ACE2 function, the SARS-CoV-2 entry receptor, predisposes to more severe disease and it appears to often occur in the relevant risk factors. Further, the effect of RAASi on ACE2 expression and on COVID-19 severity and the overall clinical implications are discussed.

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Colorectal Cancer that Highly Express Both ACE2 and TMPRSS2, Suggesting Severe Symptoms to SARS-CoV-2 Infection

Cited by 6 publications

References 10 publications

Transmembrane serine protease 2, a SARS-CoV-2 internalization protease, correlates with clinical outcome, molecular features, and immunotherapy response in colorectal cancer

Transmembrane serine protease 2, a SARS-CoV-2 internalization protease, correlates with clinical outcome, molecular features, and immunotherapy response in colorectal cancer

Potential therapeutic strategies for quercetin targeting critical pathological mechanisms associated with colon adenocarcinoma and COVID-19

ACE2, the Counter-Regulatory Renin–Angiotensin System Axis and COVID-19 Severity

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