Altered expression of 17‑β‑hydroxysteroid dehydrogenase type2 and its prognostic significance in non‑small cell lung cancer.

Abstract

Numerous studies have reported that oestrogens may contribute to the development of non small cell lung cancer (NSCLC). Although different steroidogenic enzymes have been detected in the lung, the precise mechanism leading to an exaggerated accumulation of active oestrogens in NSCLC remains unexplained. 17 β Hydroxysteroid dehydro genase type 2 (HSD17B2) is an enzyme involved in oestrogen and androgen inactivation by converting 17 β oestradiol into oestrone, and testosterone into 4 androstenedione. Therefore, the enzyme serves an important role in regulation of the intra cellular availability of active sex steroids. This study aimed to determine the expression levels of HSD17B2 in lung cancer (LC) and adjacent histopathologically unchanged tissues obtained from 161 patients with NSCLC, and to analyse the association of HSD17B2 with clinicopathological features. For that purpose, reverse transcription quantitative PCR, western blotting and immunohistochemistry were conducted. The results revealed that the mRNA and protein expression levels of HSD17B2 were significantly decreased in LC tissues compared with matched controls (P<10 6). Conversely, strong cytoplasmic staining of HSD17B2 was detected in the unchanged respiratory epithelium and in glandular cells. Notably, a strong association was detected between reduced HSD17B2 expression and advanced tumour stage, grade and size. Furthermore, it was revealed that HSD17B2 may have potential prognostic significance in NSCLC. A log-rank test revealed the benefit of high HSD17B2 protein expression for the overall survival (OS) of patients (P=0.0017), and multivariate analysis confirmed this finding (hazard ratio=0.21; 95% confidence interval=0.07-0.63; P=0.0043). Stratified analysis in the Kaplan Meier Plotter database indicated that patients with higher HSD17B2 expression presented better OS and post-progression survival. This beneficial effect was particularly evident in patients with adenocarcinoma and during the early stages of NSCLC. Decreased expression of HSD17B2 appears to be a frequent feature in NSCLC. Retrospective analysis suggests that the HSD17B2 mRNA and protein status might be independent prognostic factors in NSCLC and should be further investigated.