17β hydroxysteroid dehydrogenase type 12 (HSD17B12) is a marker of poor prognosis in ovarian carcinoma

Abstract

Objective 17β-hydroxysteroid dehydrogenase isoform 12 (HSD17B12) overexpression is associated with poor clinical outcome in invasive ductal carcinoma of the breast. Here, we evaluated HSD17B12 overexpression and its activity in ovarian carcinoma (OvCa) to determine its role in growth and progression of this tumor. Methods Immunohistochemical analysis of HSD17B12 expression was performed in 100 tissue samples of untreated OvCa and was correlated with clinicopathologic characteristics and patient outcome. In A2780 OvCa cell line expressing HSD17B12, siRNA knockdown of the enzyme was performed, and its effects on tumor cell growth and Annexin V binding were determined. Results HSD17B12 expression was detected in all tumor samples, but the staining intensity was variable. Normal ovarian epithelium was negative. Patients with tumor showing weak/moderate expression of HSD17B12 had a better overall survival than those with strongly positive tumors (p<0.001). The time to first recurrence was longer for patients with tumors with heterogenous staining relative to patients with tumors that were uniformly positive (p<0.001). Upon silencing of HSD17B12 in tumor cells, their growth was inhibited (p<0.005) and apoptosis was increased (p<0.05). Arachidonic acid but not estradiol reversed the growth inhibition mediated by HSD17B12 knockdown. Conclusion HSD17B12 overexpression is shown to be a marker of poor survival in patients with OvCa. Expression in the tumor and function of this enzyme facilitates OvCa progression.

Impact of 17β-HSD12, the 3-ketoacyl-CoA reductase of long-chain fatty acid synthesis, on breast cancer cell proliferation and migration

“…Of the four enzymatic entities participating in LCFA synthesis, 17β-HSD12 has garnered attention regarding its role in cancer through studies yielding conflicting results. While some studies reported an association of 17β-HSD12 with more aggressive tumor progression and poor outcome [21][22][23], others found a suppressive role [25]. Using different breast cancer cells, we showed that silencing of 17β-HSD12 either increases or decreases cancer cell proliferation and migration depending on the cellular context.…”

“…Interestingly, in two earlier reports, silencing of 17β-HSD12 expression, the enzyme performing the first reduction step in LCFA elongation (Fig. 1a), in one breast cancer and one ovarian cell line led to decreased proliferation, which could be reverted by AA supplementation [21,22]. These and one additional study found a correlation between high 17β-HSD12 expression and poor prognosis for survival in patients with breast and ovarian tumors [23].…”

“…High 17β-HSD12 expression has been associated with poor prognosis in breast and ovarian cancer patients [21][22][23].…”

Candidate Gene Association Analysis of Neuroblastoma in Chinese Children Strengthens the Role of LMO1

“…The HSD17B12 gene encodes human 17 beta-hydroxysteroid dehydrogenase type 12, an enzyme involved in lipid metabolism [ 25 ]. Previous studies revealed that HSD17B12 could be a prognosis marker for several human cancers [ 26 – 28 ]. A recent study by Nguyễn et al showed that SNPs in HSD17B12 were associated with low-risk NBs, and rs11037575 was the most significant SNP in the HSD17B12 gene [ 11 ].…”

Biological markers of prognosis, response to therapy and outcome in ovarian carcinoma

“…In the normal ovary HSD17B is detected in granulosa cells of developing follicles, but not in the surface epithelium. In contrast, epithelial OvCa is positive for HSD17B, and its expression in OvCa is associated with poor prognosis [40]. The clinical implications attributed to HSD17B12 overexpression in OvCa suggest that it could serve not only as biomarker but also as candidate for T-cell based immunotherapy [41].…”