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The association between HPV gene expression, inflammatory agents and cellular genes involved in EMT in lung cancer tissue.

ABSTRACT: BACKGROUND:Lung cancer is a leading cause of cancer morbidity and mortality worldwide. Several studies have suggested that Human papillomavirus (HPV) infection is an important risk factor in the development of lung cancer. In this study, we aim to address the role of HPV in the development of lung cancer mechanistically by examining the induction of inflammation and epithelial-mesenchymal transition (EMT) by this virus. METHODS:In this case-control study, tissue samples were collected from 102 cases with lung cancer and 48 controls. We examined the presence of HPV DNA and also the viral genotype in positive samples. We also examined the expression of viral genes (E2, E6 and E7), anti-carcinogenic genes (p53, retinoblastoma (RB)), and inflammatory cytokines in HPV positive cases. RESULTS:HPV DNA was detected in 52.9% (54/102) of the case samples and in 25% (12/48) of controls. A significant association was observed between a HPV positive status and lung cancer (OR?=?3.37, 95% C.I?=?1.58-7.22, P?=?0.001). The most prevalent virus genotype in the patients was type 16 (38.8%). The expression of p53 and RB were decreased while and inflammatory cytokines were increased in HPV-positive lung cancer and HPV-positive control tissues compared to HPV-negative lung cancer and HPV-negative control tissues. Also, the expression level of E-cad and PTPN-13 genes were decreased in HPV- positive samples while the expression level of SLUG, TWIST and N-cad was increased in HPV-positive samples compared to negative samples. CONCLUSION:Our study suggests that HPV infection drives the induction of inflammation and EMT which may promote in the development of lung cancer.

SUBMITTER: Rezaei M

PROVIDER: S-EPMC7517685 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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The association between HPV gene expression, inflammatory agents and cellular genes involved in EMT in lung cancer tissue.

Rezaei Marzieh M Mostafaei Shayan S Aghaei Amir A Hosseini Nayyerehalsadat N Darabi Hassan H Nouri Majid M Etemadi Ashkan A Neill Andrew O' AO Nahand Javid Sadri JS Mirzaei Hamed H Donnelly Seamas C SC Doroudian Mohammad M Moghoofei Mohsen M

BMC cancer 20200924 1

<h4>Background</h4>Lung cancer is a leading cause of cancer morbidity and mortality worldwide. Several studies have suggested that Human papillomavirus (HPV) infection is an important risk factor in the development of lung cancer. In this study, we aim to address the role of HPV in the development of lung cancer mechanistically by examining the induction of inflammation and epithelial-mesenchymal transition (EMT) by this virus.<h4>Methods</h4>In this case-control study, tissue samples were colle ...[more]

PMID: 32972386

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Project description:ImportanceCirculating tumor tissue-modified viral (TTMV) human papillomavirus (HPV) DNA is a dynamic, clinically relevant biomarker for HPV-positive oropharyngeal squamous cell carcinoma. Reasons for its wide pretreatment interpatient variability are not well understood.ObjectiveTo characterize clinicopathologic factors associated with TTMV HPV DNA.Design, setting, and participantsThis cross-sectional study included patients evaluated for HPV-positive oropharyngeal squamous cell carcinoma at Dana-Farber Cancer Institute in Boston, Massachusetts, between December 2019 and January 2022 and who were undergoing curative-intent treatment.ExposuresClinicopathologic characteristics including demographic variables, tumor and nodal staging, HPV genotype, and imaging findings.Main outcomes and measuresPretreatment circulating TTMV HPV DNA from 5 genotypes (16, 18, 31, 33, and 35) assessed using a commercially available digital droplet polymerase chain reaction-based assay, considered as either detectable/undetectable or a continuous score (fragments/mL).ResultsAmong 110 included patients, 96 were men (87%) and 104 were White (95%), with a mean (SD) age of 62.2 (9.4) years. Circulating TTMV HPV DNA was detected in 98 patients (89%), with a median (IQR) score of 315 (47-2686) fragments/mL (range, 0-60 061 fragments/mL). Most detectable TTMV HPV DNA was genotype 16 (n = 86 [88%]), while 12 patients (12%) harbored other genotypes. Circulating TTMV HPV DNA detection was most strongly associated with clinical N stage. Although few patients had clinical stage N0 disease, only 4 of these 11 patients (36%) had detectable DNA compared with 94 of 99 patients (95%) with clinical stage N1 to N3 disease (proportion difference, 59%; 95% CI, 30%-87%). Among patients with undetectable TTMV HPV DNA, more than half (7 of 12 [58%]) had clinical stage N0 disease. The TTMV HPV DNA prevalence and score increased with progressively higher clinical nodal stage, diameter of largest lymph node, and higher nodal maximum standardized uptake value on positron emission tomography/computed tomography. In multivariable analysis, clinical nodal stage and nodal maximum standardized uptake value were each strongly associated with TTMV HPV DNA score. Among 27 surgically treated patients, more patients with than without lymphovascular invasion had detectable TTMV HPV DNA (12 of 12 [100%] vs 9 of 15 [60%]).Conclusions and relevanceIn this cross-sectional study, circulating TTMV HPV DNA was statistically significantly associated with nodal disease at HPV-positive OPSCC diagnosis. The few patients with undetectable levels had predominantly clinical stage N0 disease, suggesting assay sensitivity for diagnostic purposes may be lower among patients without cervical lymphadenopathy. Mechanisms underlying this association, and the use of this biomarker for surveillance of patients with undetectable baseline values, warrant further investigation.

Dataset Information

The association between HPV gene expression, inflammatory agents and cellular genes involved in EMT in lung cancer tissue.

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The association between HPV gene expression, inflammatory agents and cellular genes involved in EMT in lung cancer tissue.

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