Altered expression of 17‑β‑hydroxysteroid dehydrogenase type�2 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 dehydrogenase 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 intracellular 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.

Long non‐coding RNA LGALS8‐AS1 facilitates PLAGL2‐mediated malignant phenotypes in gastric cancer

“…The Kaplan–Meier plotter survival tool evaluated the correlation between more than 30 thousand gene expression and survival in 21 tumors, including breast cancer, lung cancer, GC, etc. Some of the survival data were derived from TCGA database and were also widely used in the basic research of cancer 28–31 . In the present study, we identified a novel GC‐related lncRNA LGALS8‐AS1 through TCGA database combined with the Kaplan–Meier plotter survival tool.…”

“…Some of the survival data were derived from TCGA database and were also widely used in the basic research of cancer. [28][29][30][31] In the present study, we identified a novel GC-related lncRNA LGALS8-AS1 through TCGA database combined with the Kaplan-Meier plotter survival tool.…”

Comparative RNA-sequencing analysis of the prostate in a mouse model of benign prostatic hyperplasia with bladder outlet obstruction

“…For example, in the lncRNA-related ceRNA network, NEAT1 can regulate the expression of Hsd17b2, an mRNA related to steroid metabolism, via miR-181a-5p [ 86 ]. Steroid hormones were inactivated by HSD17B2, and their balance was regulated in a variety of tissues by this molecule [ 87 ]. The elevation in HSD17B2 levels may have been due to the supraphysiological dose of steroid hormone used in this experiment.…”

“…The elevation in HSD17B2 levels may have been due to the supraphysiological dose of steroid hormone used in this experiment. In the circRNA-related reRNA network, circRNA Snx5 regulates Aldh1a2 (a retinoic acid synthase) via miR-129-5p, and elevated Aldh1a2 promotes retinoic acid synthesis, while retinoic acid (a vitamin A metabolite) also exhibits anti-inflammatory effects by preventing oxidative stress [ 87 ]; these findings suggest feedback regulation by mouse prostate tissue in response to intense oxidative stress. The above findings also suggest that steroid hormone-induced BPH in mice was regulated by a dynamic balance of oxidative stress and antioxidative stress.…”

17β-Hydroxysteroid Dehydrogenase Type 1 Inhibition: A Potential Treatment Option for Non-Small Cell Lung Cancer

“…17β-HSD1 catalyzes the conversion of the weakly active E1 to the potent E2, and 17β-HSD2 is its biological counterpart. The expression levels of these enzymes were found to be altered in NSCLC cells compared to healthy tissue, providing a significant prognostic factor and contributing to tumor progression in a stimulatory fashion, probably by increasing the E2/E1 ratio. − Selective inhibition of 17β-HSD1 seems therefore a potential approach for the treatment of NSCLC and might be superior to aromatase inhibition in terms of potential side effects: 17β-HSD1 inhibition would result in only a local, intracellular drop in estradiol levels in the target cells while aromatase inhibition would decrease systemic circulating estradiol levels.…”