LncRNA GAS5 enhances tumor stem cell-like medicated sensitivity of paclitaxel and inhibits epithelial-to-mesenchymal transition by targeting the miR-18a-5p/STK4 pathway in prostate cancer.

The onset of prostate cancer (PCa) is often hidden, and recurrence and metastasis are more likely to occur due to chemotherapy resistance. Herein, we identified downregulated long noncoding RNA (lncRNA) growth arrest-specific 5 (GAS5) in PCa that was associated with metastasis and paclitaxel resistance. GAS5 acted as a tumor suppressor in suppressing the proliferation and metastasis of paclitaxel-resistant PCa cells. GAS5 overexpression in vivo inhibited the tumor growth of xenografts and elevated PCa sensitivity to paclitaxel. Combination of GAS5 and paclitaxel treatment showed great potential in PCa treatment. Moreover, mechanistic analysis revealed a novel regulatory network of GAS5/miR-18a-5p/serine/threonine kinase 4 (STK4) that inhibits epithelial-to-mesenchymal transition (EMT) and enhances tumor stem cell-like-mediated sensitivity to paclitaxel in PCa. These findings provide a novel direction for the development of a potential adjunct to cancer chemotherapy that aims to improve the sensitivity of chemotherapy drugs in PCa.

[Predictive factors for clinically significant elevation of post-prostatectomy Gleason score in patients with biopsy Gleason score ≤7].

OBJECTIVE: To investigate the prognostic factors for clinically significant increase in post-prostatectomy Gleason score (pGS) in patients with biopsy Gleason score (bGS) ≤7. METHODS: This retrospective study included 170 cases of prostate cancer treated by radical prostatectomy in our hospital from January 2010 to December 2017. We analyzed the clinical and pathological data on the patients, including the age, preoperative serum tPSA, fPSA, fPSA / tPSA, prostate volume, PSA density (PSAD), and positive puncture rate of the patients with clinically significant elevation of pGS, as well as the possible factors for clinically significant pGS increase in patients with bGS = 7 and those with bGS ≤ 6. RESULTS: The pGS was found consistent with the bGS in 95 (55.9%) of the 170 patients, decreased in 11 (6.5%) and increased in 64 (37.6%). Among those with elevated pGS, 55 (32.4%) were shown with and the other 9 (5.3%) without clinical significance. Clinically significant escalation of pGS was markedly correlated with the positive puncture rate in the patients with bGS = 7 (P = 0.021) and with the age (P = 0.018) and PSAD (P = 0.033) of those with bGS ≤ 6. ROC curve analysis further showed the positive puncture rate > 0.528 in the patients with bGS = 7 and a higher risk of clinically significant pGS increase in those aged > 64.5 years with bGS ≤ 6 and PSAD > 0.267 µg/(L·g). CONCLUSIONS: Clinically significant elevation of pGS is correlated with the rate of positive punctures in prostate cancer patients with bGS = 7 and with age and PSAD in those with bGS ≤ 6.