Cathepsin B is a potential therapeutic target for coronavirus disease 2019 patients with lung adenocarcinoma.

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Hospitalization and mortality rates of lung cancer patients diagnosed with COVID-19 are higher than those of patients presenting with other cancers. However, the reasons for the outcomes being disproportionately severe in lung adenocarcinoma (LUAD) patients with COVID-19 remain elusive. The present study aimed to identify the possible causes for disproportionately severe COVID-19 outcomes in LUAD patients and determine a therapeutic target for COVID-19 patients with LUAD. We used publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and various bioinformatics tools to identify and analyze the genes implicated in SARS-CoV-2 infection in LUAD patients. Upregulation of the SARS-CoV-2 infection-related molecules dipeptidyl peptidase 4, basigin, cathepsin B (CTSB), methylenetetrahydrofolate dehydrogenase, and peptidylprolyl isomerase B rather than angiotensin-converting enzyme 2 may explain the relatively high susceptibility of LUAD patients to SARS-CoV-2 infection. CTSB was highly expressed in the LUAD tissues after SARS-CoV-2 infection, and its expression was positively correlated with immune cell infiltration and proinflammatory cytokine expression. These findings suggest that CTSB plays a vital role in the hyperinflammatory response in COVID-19 patients with LUAD and is a promising target for the development of a novel drug therapy for COVID-19 patients.", "claims": [{"id": "claim-method", "statement": "Log-rank tests with Cox proportional hazard ratio (HR) and 95% confidence intervals (CIs) were performed.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35007526", "locator": "sections[9] \"Prognostic value analysis\" paragraph 2", "quote": "Log-rank tests with Cox proportional hazard ratio (HR) and 95% confidence intervals (CIs) were performed."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data supporting the findings of the present study are available in the article itself and the Supplementary Material. They are also available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35007526", "locator": "sections[16] \"Data availability statement\" paragraph 2", "quote": "Data supporting the findings of the present study are available in the article itself and the Supplementary Material. They are also available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "CTSB upregulation was significantly associated with poor prognosis in the OS (HR [95% CI] = 5.42 [2.53–11.58], Cox P = 0.000013) and RFS (HR [95% CI] = 4.04 [2.34–6.99], Cox P = 0.000001) of LUAD patients (Fig. 6C).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "CTSB upregulation was significantly associated with poor prognosis in the OS (HR [95% CI] = 5.42 [2.53–11.58], Cox P = 0.000013) and RFS (HR [95% CI] = 4.04 [2.34–6.99], Cox P = 0.000001) of LUAD patients (Fig. 6C)."}, "evidence": [{"asset": "source:pmid:35007526", "locator": "sections[14] \"Elevated CTSB expression promoted immune cell infiltration and was associated with poor prognosis in patients with LUAD\" paragraph 5", "quote": "CTSB upregulation was significantly associated with poor prognosis in the OS (HR [95% CI] = 5.42 [2.53–11.58], Cox P = 0.000013) and RFS (HR [95% CI] = 4.04 [2.34–6.99], Cox P = 0.000001) of LUAD patients (Fig. 6C)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "CTSB upregulation was significantly associated with poor prognosis in the OS (HR [95% CI] = 5.42 [2.53–11.58], Cox P = 0.000013) and RFS (HR [95% CI] = 4.04 [2.34–6.99], Cox P = 0.000001) of LUAD patients (Fig. 6C).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35007526"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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