Identification and Validation of a Prognostic Signature for Prostate Cancer Based on Ferroptosis-Related Genes.

Ferroptosis, an iron-dependent form of selective cell death, is involved in the development of many cancers. However, ferroptosis related genes (FRGs) in prostate cancer (PCa) are not been well studied. In this study, we collected the mRNA expression profiles and clinical information of PCa patients from TCGA and MSKCC databases. The univariate, LASSO, and multivariate Cox regression analyses were performed to construct a prognostic signature. Seven FRGs, AKR1C3, ALOXE3, ATP5MC3, CARS1, MT1G, PTGS2, and TFRC, were included to establish a risk model, which was validated in the MSKCC dataset. The results showed that the high-risk group was apparently correlated with copy number alteration load, tumor burden mutation, immune cell infiltration, mRNAsi, immunotherapy, and bicalutamide response. Moreover, we found that TFRC overexpression induced the proliferation and invasion of PCa cell lines in vitro. These results demonstrate that this risk model can accurately predict prognosis, suggesting that FRGs are promising prognostic biomarkers and potential drug targets in PCa patients.

Characteristics and risk differences of different tumor size on localized prostate cancer: A retrospective cohort study in the SEER database.

OBJECTIVE: We aimed to evaluate the role of tumor size in predicting tumor risk for localized prostate cancer (PCa) patients undergoing radical prostatectomy (RP). METHODS: Twenty-five thousand, one hundred twenty-seven men with PCa receiving RP from 2010 to 2015 were extracted from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier plots and multivariable Cox regression analyses were used to illustrate overall survival (OS) according to the tumor size. The tumor size was confirmed by postoperative pathology after RP. RESULTS: Among overall localized PCa, 84.6% were high-risk PCa, 9.2% were intermediate-risk PCa, and 6.2% were low-risk PCa. Multivariate analyses demonstrated that tumor size ≥21 mm was an independent risk predict factor of low-risk PCa (odds ratio [OR]: 11.940; 95% CI, 9.404-15.161; p < 0.001) and intermediate-risk PCa (OR: 1.887; 95% CI, 1.586-2.245; p < 0.001). Tumor sizes ≤5 mm significantly correlated with high-risk PCa (p < 0.001). Tumor size ≤5 mm had the worst OS in overall localized PCa and high-risk PCa (p < 0.001). CONCLUSIONS: In localized PCa, tumor sizes ≥21 mm may help predict low or intermediate-risk PCa, while tumor sizes ≤5 mm might help predict high-risk PCa. In clinical practice, we should be on high alert for patients with tumors size ≤5 mm due to its poor prognosis after RP.

Erratum: Silencing miR-454 suppresses cell proliferation, migration and invasion via directly targeting MECP2 in renal cell carcinoma.

[This corrects the article on p. 4277 in vol. 12, PMID: 32913504.].

Incidental para-ureteral aggressive angiomyxoma: a rare case report and literature review.

BACKGROUND: Aggressive angiomyxoma (AA) is a rare tumor that typically occurs in the pelvis and perineum, most commonly in women of reproductive age. However, no para-ureteral AA has been reported according to the literature. Case presentation We herein describe the first case of para-ureteral AA. A 62-year-old male presented to our institute in March 2017 with a para-ureteral mass that was 15 mm in diameter incidentally. No symptom was observed and laboratory analysis was unremarkable. Magnetic resonance and computed tomography imaging showed a non-enhancing mass abutting the left ureter without causing obstruction. Laparoscopic resection of the mass was performed without injury to the ureter. Pathologic and immunohistochemical results were consistent with AA. Till now, no recurrence was noticed. CONCLUSIONS: We reported a rare case of para-ureteral AA, along with a literature review. Early diagnosis, proper surgical plan and long-term close follow-up is recommended for its high risk of recurrence and malignant potential.

Silencing miR-454 suppresses cell proliferation, migration and invasion via directly targeting MECP2 in renal cell carcinoma.

Renal cell cancer (RCC) is one of the most common malignant tumors of the urinary system. MicroRNA-454 (miR-454) has been reported to play an important role in various cancer progressions, such as hepatocellular carcinoma, breast cancer and glioblastoma. Nevertheless, its effect on RCC still remains unknown. We aimed to investigate the biological function and underlying mechanisms of miR-454 in RCC. The expressions of miR-454 and MECP2 in RCC tissues were assessed using data from TCGA database and our own clinical samples. Functional experiments Cell Counting Kit-8 (CCK-8), colony formation, wound healing and Transwell assays were applied to detect the effects of miR-454 and MECP2 in RCC. The interaction between miR-454 and MECP2 was assessed by western blot and luciferase reporter assays. MiR-454 was upregulated in RCC tissues and cell lines compared with matched adjacent normal tissues and the normal kidney tubular epithelial cell line HK-2. MiR-454 inhibition and methyl-CpG binding protein 2 (MECP2) overexpression could both decrease the proliferative, migrative and invasive abilities of RCC cells. Higher expression of miR-454 predicted a poor overall survival (OS) (HR: 1.8; P < 0.05), while MECP2 level was positively related with RCC OS (HR: 0.55; P < 0.05) and disease-free survival (HR: 0.56; P < 0.05). Mechanistically, we showed that miR-454 could directly target the downstream gene MECP2. Our findings indicated that miR-454 accelerates RCC progression via suppressing MECP2 expression, which may provide a novel potential target of RCC treatment in the future.

Perioperative Chemotherapy on Survival in Patients With Upper Urinary Tract Urothelial Carcinoma Undergoing Nephroureterectomy: A Population-Based Study.

Objectives: To estimate the stage-specific impact of perioperative chemotherapy on survival for upper urinary tract urothelial carcinoma (UTUC) patients treated with nephroureterectomy (NU). Methods: Overall, 7,278 UTUC patients treated with NU from 2004 to 2015 were identified within the SEER database. Kaplan-Meier plots were used to elucidate overall survival (OS) and cancer-specific survival (CSS) rates. Multivariable Cox regression analyses were used to test the impact of chemotherapy on survival rates, after stratifying according to pathological stage. Results: Chemotherapy was performed in 17.3% of patients and in 5.7, 11.5, 25.4, and 51.3% of patients with, respectively, pT1, pT2, pT3, and pT4 disease (P < 0.001). In multivariable analyses, perioperative chemotherapy was associated with a lower OS in pT2 patients and a lower CSS in pT1 disease (both P < 0.05), while predisposed to a higher OS in pT3 and pT4 patients (both P < 0.01). Moreover, perioperative chemotherapy was prone to a higher OS or CSS in pN+ disease compared to no chemotherapy (both P < 0.01). Conclusion: Perioperative chemotherapy was more frequently performed in locally advanced UTUC patients. The beneficial effect of chemotherapy on OS was evident in pT3/pT4 and pN+ patients. In addition, a clear CSS benefit was observed in patients who received chemotherapy for pN+ UTUC, while perioperative chemotherapy may reduce CSS for pT1 and OS for pT2 patients following NU.

Impact of peri-prostatic fat measurements using MRI on the prediction of prostate cancer with transrectal ultrasound-guided biopsy.

OBJECTIVES: To estimate the impact of peri-prostatic fat (PPF) measurements using preoperative magnetic resonance imaging on the prediction of prostate cancer (PCa) with transrectal ultrasound-guided biopsy. PATIENTS AND METHODS: We performed a retrospective 2-center study on 660 consecutive patients receiving transrectal ultrasound-guided biopsy-biopsy from June 2016 to October 2018. Pathologic and immunohistochemical characteristics were collected. PPF measurements including PPF area (PPFA) and PPFA to prostate area (PA) ratio (PPFA/PA) were assessed by preoperative staging magnetic resonance imaging. Clinical variables were correlated with Gleason score by using Spearman (ρ) correlation coefficients. Multivariable analysis was performed to identify independent predictors of PCa. The diagnostic performance was estimated using ROC curves. RESULTS: The Gleason score was significantly correlated with age (ρ = 0.114, P = 0.035), prostate-specific antigen (PSA) (ρ = 0.482, P < 0.001), PIRADS scoring (ρ = 0.403, P < 0.001) and PPFA/PA (ρ = 0.238, P < 0.001). Multivariate analysis revealed that PPFA/PA, age, digital rectal examination, family history of PCa, PSA, and PIRADS scoring were independently predictive of PCa. The ROC AUC to detect PCa or clinically significant PCa (CS-PCa; Gleason Score 3 + 4 or greater) improved with the addition of PPFA/PA (PCa: 0.93 vs. 0.89; CS-PCa: 0.92 vs. 0.90). CONCLUSION: PPFA/PA is an independent predictor for PCa along with age, digital rectal examination, family history of PCa, PSA, and PIRADS scoring. PPF measurements especially PPFA/PA may help detect PCa or CS-PCa, thus helping improve PCa risk stratification and screening to avoid unnecessary biopsies.

Effect of lymph node dissection on stage-specific survival in patients with upper urinary tract urothelial carcinoma treated with nephroureterectomy.

BACKGROUND: We aimed to estimate the stage-specific impact of lymph node dissection (LND) on survival for upper urinary tract urothelial carcinoma (UTUC) patients treated with nephroureterectomy (NU). METHODS: Overall, 7278 UTUC patients undergoing NU within the SEER database from 2004 to 2015 were identified. Kaplan-Meier plots illustrated overall survival (OS) and cancer-specific survival (CSS) rates according to LND status. Multivariable Cox regression analyses assessed the effect of LND on OS and CSS rates stratified by pathological tumor stage. RESULTS: LND was performed in 26.9% of patients, and in 18.6, 23.3, 31.2 and 45.9% for pT1, pT2, pT3 and pT4 patients, respectively (P <  0.001). In multivariable Cox regression analyses, LND was associated with a higher OS or CSS in UTUC patients with pT3 and pT4 disease (all P <  0.05), but failed to achieve independent predictor status in patients with pT1 and pT2 disease (all P > 0.05). LND with 1 to 3 regional lymph nodes removed was prone to a higher OS or CSS only in pT4 compared to no LND (both P <  0.01). LND with 4 or more regional lymph nodes removed predisposed to a higher OS or CSS in pT3 or pT4 (all P <  0.05). CONCLUSIONS: The beneficial effect of LND especially LND with 4 or more regional lymph nodes removed on survival was evident in pT3/4 patients. LND can be considered for pT3 and pT4, for pT1/2 remains to be seen, both of which will be verified by further prospective studies.

Elevated visceral fat area is associated with adverse postoperative outcome of radical colectomy for colon adenocarcinoma patients.

OBJECTIVE: To assess the impact of visceral obesity quantified by preoperative computed tomography on short-term postoperative outcomes compared with body mass index (BMI) in stage I-III colon adenocarcinoma patients. METHODS: In this retrospective study, 107 patients treated with radical colectomy for stage I-III colon adenocarcinoma were classified as obese or non-obese by computed tomography-based measures or BMI (obese: BMI ≥28 kg/m2 , visceral fat area (VFA) to subcutaneous fat area ratio (V/S) ≥0.4, and VFA ≥100 cm2 ). Clinical variables, operation time, estimated blood loss, pathologic stage, histologic grade, postoperative complications, postoperative stay and hospitalization expenses were compared. RESULTS: Obese patients by VFA were more likely to have higher postoperative complication rate (32.9 versus 11.8%, P = 0.021), have longer operation time (184.6 ± 49.5 versus 163.1 ± 44.1 min, P = 0.033), postoperative stay (15.21 ± 7.59 versus 12.29 ± 5.40 days, P = 0.047) and cost more ($10 758.7 ± 3271.7 versus $9232.0 ± 2994.6, P = 0.023) than non-obese. CONCLUSION: Visceral obesity graded by VFA is associated with increased postoperative morbidity, operation time, postoperative stay and hospitalization expenses for colon adenocarcinoma patients and may be superior to BMI or V/S for the prediction of colon surgery.