These data collectively showing that KLF9 substantially inhibits AKT activation and abrogates tumor growth of PCa cells, suggest the potential of either genetic or pharmacological activation of KLF9 in the therapeutic treatment of castration-resistant PCa.

Prostate cancer is a heterogeneous disease and optimum gene targeting treatment is often impermissible. We aim to determine the intratumoral genomic heterogeneity of prostate cancer and explore candidate genes for targeted therapy. Exome sequencing was performed on 37 samples from 16 patients with prostate cancer. Somatic variant analysis, copy number variant (CNV) analysis, clonal evolution analysis and variant spectrum analysis were used to study the intratumoral genomic heterogeneity and genetic characteristics of metastatic prostate cancer. Our study confirmed the high intratumoral genetic heterogeneity of prostate cancer in many aspects, including number of shared variants, tumor mutation burden (TMB), variant genes, CNV burden, weighted genome instability index (wGII), CNV profiles, clonal evolutionary process, variant spectrum and mutational signatures. Moreover, we identified several common genetic characteristics of prostate cancer. Alterations of DNA damage repair genes, RTK/RAS pathway associated gene RASGRF1 and autophagy gene EPG5 may be involved in tumorigenesis in prostate cancer. CNV burden and DNA damage repair (DDR) genes may be associated with metastasis of prostate cancer.B.W., X.L. and H.S. contributed equally to this work Additional Supporting Information may be found in the online version of this article.

Kruppel-like factors (KLFs) play an important role in many biological processes including cell proliferation, differentiation and development. Our study showed that the level of KLF9 is lower in PCa cell lines compared to a benign prostate cell line; the androgen-independent cell line PC3 expresses significantly lower KLF9 than the androgen-dependent cell line, LNCaP. Forced overexpression of KLF9 suppressed cell growth, colony formation, and induced cell apoptosis in LNCaP cells. We also found that KLF9 expression was induced in response to apoptosis caused by flutamide, and further addition of dihydrotestosterone antagonized the action of flutamide and significantly decreased KLF9 expression. Furthermore, activation of the androgen receptor (AR) was inhibited by the overexpression of KLF9. Our research shows that KLF9 is lower in androgen-independent cell lines than in androgen-dependent cell lines; Overexpression of KLF9 dramatically suppresses the proliferation, anchorage-independent growth, and induces apoptosis in androgen-dependent cells; KLF9 inhibition on prostate cancer cell growth may be acting through the AR pathway. Our results therefore suggest that KLF9 may play a significant role in the transition from androgen-dependent to androgen-independent prostate cancer and is a potential target of prevention and therapy.

Background: This study aimed to investigate the characteristics and extent of glycometabolism impairment in patients with adrenal diseases, including Cushing syndrome, primary aldosteronism, pheochromocytoma, and nonfunctional adrenal incidentaloma. Methods: This study enrolled thirty-two patients with adrenal diseases as adrenal disease groups and eight healthy individuals as healthy controls. Blood glucose levels were indicated by glucose concentration in interstitial fluid, which was documented using flash glucose monitoring system. According to flash glucose monitoring system data, parameters representing general blood glucose alterations, within-day and day-today glucose variability, and glucose-target-rate were calculated. Furthermore, blood glucose levels at nocturnal, fasting, and postprandial periods were analyzed. Besides, islet b-cell function and insulin resistance were assessed.

Background Dealing with the giant pheochromocytomas (maximum diameter ≥ 6cm) has long been a tough challenge for urologists. We introduced a new retroperitoneoscopic adrenalectomy method modified with renal-rotation techniques to treat giant pheochromocytomas. Methods 28 diagnosed patients were prospectively recruited as the intervention group. Meanwhile, by referring to the historical records in our database, matched patients who had undergone routine retroperitoneoscopic adrenalectomy (RA), transperitoneal laparoscopic adrenalectomy (TA), or open adrenalectomy (OA) for giant pheochromocytomas were selected as controls. Perioperative and follow-up data were collected for comparative assessment. Results Among all the groups, the intervention group had the minimal bleeding volume (28.93 ± 25.94 ml, p < 0.05), the least intraoperative blood pressure variation (59.11 ± 25.68 mmHg, p < 0.05), the shortest operation time (115.32 ± 30.69 mins, p < 0.05), the lowest postoperative ICU admission rates (7.14%, p < 0.05), and shortest drainage time length (2.57 ± 0.50 days, p < 0.05). Besides, compared with TA and OA groups, intervention group was also characterized by lower pain scores (3.21 ± 0.63, p < 0.05), less postoperative complications (p < 0.05), earlier diet initiation time (1.32 ± 0.48 postoperative days, p < 0.05) and ambulation time (2.68 ± 0.48 postoperative days, p < 0.05). Follow-up blood pressure and metanephrine and normetanephrine levels in all intervention group patients remained normal. Conclusion Compared with RA, TA, and OA, retroperitoneoscopic adrenalectomy with renal-rotation techniques is a more feasible, efficient, and secure surgical treatment for giant pheochromocytomas. Trial registration: This study has been prospectively registered on the Chinese Clinical Trial Registry website (ChiCTR2200059953, date of first registration: 14/05/2022).