Dataset Information

SLPI and AnxA2 expression in neoplasm-free palatine tonsils is associated with smoking habit of individuals.

ABSTRACT: In order to confirm the inverse correlation between secretory leucocyte protease inhibitor (SLPI) expression, and human papillomavirus (HPV) infection previously observed in head and neck squamous-cell carcinoma, the present study retrospectively investigated the association between SLPI and Annexin A2 (AnxA2) expression, and HPV status in non-neoplastic chronic tonsillitis (n=118), and tonsillar hyperplasia (n=96) tissue. We hypothesised that smoking induces the upregulation of SLPI, resulting in reduced binding of HPV to AnxA2, a known modulator of HPV entry into the cell. SLPI and cyclin-dependent kinase inhibitor 2A (p16INK4A) protein expression was measured using immunohistochemistry in 214 specimens; SLPI and AnxA2 gene expression was measured using reverse transcription-quantitative polymerase chain reaction in 213 cases; and DNA was isolated from all the specimens to determine HPV status. The association between the results of the aforementioned analyses and the smoking habits of patients was analysed. The samples were HPV-negative. p16INK4A expression demonstrated moderate and strong staining in 38, and 0 cases, respectively. SLPI expression presented negative, weak and moderate signals in 163, 45, and 6 cases, respectively. A positive correlation was identified between smoking and SLPI (P=0.0001). Gene expression analysis (n=213) revealed that smoking (n=48) resulted in a significant increase in SLPI and AnxA2 expression. A significant positive correlation between AnxA2 and SLPI, indicating a surplus of AnxA2 in relation to SLPI, was exclusively identified in non-smokers. The data demonstrated that smoking results in increased SLPI and AnxA2 expression also in non-neoplastic tonsillar tissue. The observed surplus of AnxA2 in relation to SLPI identified exclusively in the tonsillar tissue of non-smokers indicates a higher possibility of a successful HPV infection of the tonsillar tissue of non-smokers, given the properties of AnxA2 to function as an infection modulator.

SUBMITTER: Quabius ES

PROVIDER: S-EPMC5547760 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:PurposeDICER1 syndrome is an autosomal-dominant, pleiotropic tumor-predisposition disorder caused by pathogenic germline variants in DICER1. We sought to quantify risk, hazard rates, and the probability of neoplasm incidence accounting for competing risks ("cumulative incidence") of neoplasms (benign and malignant) and standardized incidence ratios for malignant tumors in individuals with DICER1 pathogenic variation.Patients and methodsWe combined data from three large cohorts of patients who carry germline pathogenic variation in DICER1. To reduce ascertainment bias, we distinguished probands from nonprobands. Neoplasm diagnoses were confirmed by review of pathology reports and/or central review of surgical pathology materials. Standardized cancer incidence ratios were determined relative to the SEER program, which does not capture all DICER1-associated neoplasms. For all malignancies and benign tumors ("neoplasms," excluding type Ir pleuropulmonary blastoma and thyroid nodules), we used the Kaplan-Meier method and nonparametric cumulative incidence curves to estimate neoplasm-free survival.ResultsWe calculated the age at first neoplasm diagnosis (systematically ascertained cancers plus DICER1-associated neoplasms pleuropulmonary blastoma, cystic nephroma, and nasal chondromesenchymal hamartoma) in 102 female and male nonproband DICER1 carriers. By age 10 years, 5.3% (95% CI, 0.6% to 9.7%) of nonproband DICER1 carriers had developed a neoplasm (females, 4.0%; males, 6.6%). By age 50 years, 19.3% (95% CI, 8.4% to 29.0%) of nonprobands had developed a neoplasm (females, 26.5%; males, 10.2%). After age 10 years, female risk was elevated compared with male risk. Standardized cancer incidence ratio analysis of 102 nonproband DICER1 carriers, which represented 3,344 person-years of observation, showed significant cancer excesses overall, particularly of gynecologic and thyroid cancers.ConclusionThis work provides the first quantitative analysis of site-specific neoplasm risk and excess malignancy risk in 102 systematically characterized nonproband DICER1 carriers. Our findings inform DICER1 syndrome phenotype, natural history, and genetic counseling.

Project description:The aldokatoreductases (AKRs) represent a gene superfamily that code for monomeric, soluble NAD(P)H-dependent oxidoreductases that mediate elimination reactions. AKR1B10, an AKR that functions to eliminate retinals, has been observed to be upregulated in squamous metaplasma and non small cell lung cancer, and has been suggested as a diagnostic marker specific to tobacco-related carcinogenesis. In the context of the link of smoking and lung cancer and the enhanced expression of AKR1B10 expression in lung cancer, we hypothesize that enhanced expression of AKR1B10 may be initiated in healthy smokers, prior to the development of any evidence of lung cancer. For this purpose, expression of AKR1B10 was assessed at the mRNA level using microarrays in the large airway epithelium (21 healthy nonsmokers, 31 health smokers) and small airway epithelium (51 healthy nonsmokers, 58 healthy smokers) obtained by fiberoptic bronchoscopy and brushing, as well as assessment in a subset of this population by TaqMan PCR and in endobronchial biopsies by Western analysis and immunohistochemistry. Compared to healthy nonsmokers, ARK1B10 mRNA levels were markedly upregulated in both the large and small airway epithelium of healthy smokers (large airway microarray p<0.0001, small airway p<0.0001; TaqMan large airway, p<0.02, small airway p<0.01). Consistent with the mRNA data, AKR1B10 protein was significantly upregulated in the airway epithelium of healthy smokers as assessed by Western analysis and by immunohistochemistry, with AKR1B10 expressed in both differentiated and basal cells of the normal epithelium. Finally, cigarette smoke extract mediated up-regulation of AKR1B10 in airway epithelial cells in vitro. Thus, smoking per se mediates up-regulation of AKR1B10 expression in the airway epithelium of healthy smokers with no evidence of lung cancer. In the context of these observations, and the link of AKR1B10 to the metabolism of retinals and to lung cancer, the smoking-induced up-regulation of AKR1B10 may be an early process in the multiple events leading to the develop of lung cancer.

Dataset Information

SLPI and AnxA2 expression in neoplasm-free palatine tonsils is associated with smoking habit of individuals.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets