In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 2 ( 2023-2-21), p. e0282017-
Abstract:
The incidence and mortality rates of colorectal cancer (CRC) has been reported to be strongly associated to sex/gender difference. CRC shows sexual dimorphism, and sex hormones have been shown to affect the tumor immune microenvironment. This study aimed to investigate location-dependent sex differences in tumorigenic molecular characteristics in patients with colorectal tumors, including adenoma and CRC. Methods A total of 231 participants, including 138 patients with CRC, 55 patients with colorectal adenoma, and 38 healthy controls, were recruited between 2015 and 2021 at Seoul National University Bundang Hospital. All patients underwent colonoscopy and acquired tumor lesion samples were further analyzed for programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) expression, deficient mismatch repair (dMMR), and microsatellite instability (MSI) status. This study was registered with ClinicalTrial.gov, number NCT05638542. Results The average of combined positive score (CPS) was higher in serrated lesions and polyps (lesions/polyps) compared to conventional adenomas (5.73 and 1.41, respectively, P 〈 0.001). No significant correlation was found between sex and PD-L1 expression within the groups, regardless of histopathological diagnosis. In multivariate analysis where each sex was further stratified by tumor location due to their interaction in CRC, PD-L1 expression was inversely correlated with males having proximal CRC with a CPS cutoff of 1 (Odds ratio (OR) 0.28, P = 0.034). Females with proximal CRC showed a significant association with dMMR/MSI-high (OR 14.93, P = 0.032) and high EGFR expression (OR 4.17, P = 0.017). Conclusion Sex and tumor location influenced molecular features such as PD-L1, MMR/MSI status and EGFR expression in CRC, suggesting a possible underlying mechanism of sex-specific colorectal carcinogenesis.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0282017
DOI:
10.1371/journal.pone.0282017.g001
DOI:
10.1371/journal.pone.0282017.g002
DOI:
10.1371/journal.pone.0282017.t001
DOI:
10.1371/journal.pone.0282017.t002
DOI:
10.1371/journal.pone.0282017.t003
DOI:
10.1371/journal.pone.0282017.t004
DOI:
10.1371/journal.pone.0282017.t005
DOI:
10.1371/journal.pone.0282017.s001
DOI:
10.1371/journal.pone.0282017.s002
DOI:
10.1371/journal.pone.0282017.s003
DOI:
10.1371/journal.pone.0282017.s004
DOI:
10.1371/journal.pone.0282017.s005
DOI:
10.1371/journal.pone.0282017.s006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2267670-3
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