scholarly journals Novel Gene Signatures Predictive of Patient Recurrence-Free Survival and Castration Resistance in Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 917
Author(s):  
Jun A ◽  
Baotong Zhang ◽  
Zhiqian Zhang ◽  
Hailiang Hu ◽  
Jin-Tang Dong
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Characteristic Curve ◽  
Treatment Decision ◽  
Rank Aggregation ◽  
Lymph Node Status ◽  
Calibration Plot ◽  
Recurrence Free Survival ◽  
Castration Resistance ◽  
Free Survival

Molecular signatures predictive of recurrence-free survival (RFS) and castration resistance are critical for treatment decision-making in prostate cancer (PCa), but the robustness of current signatures is limited. Here, we applied the Robust Rank Aggregation (RRA) method to PCa transcriptome profiles and identified 287 genes differentially expressed between localized castration-resistant PCa (CRPC) and hormone-sensitive PCa (HSPC). Least absolute shrinkage and selection operator (LASSO) and stepwise Cox regression analyses of the 287 genes developed a 6-gene signature predictive of RFS in PCa. This signature included NPEPL1, VWF, LMO7, ALDH2, NUAK1, and TPT1, and was named CRPC-derived prognosis signature (CRPCPS). Interestingly, three of these 6 genes constituted another signature capable of distinguishing CRPC from HSPC. The CRPCPS predicted RFS in 5/9 cohorts in the multivariate analysis and remained valid in patients stratified by tumor stage, Gleason score, and lymph node status. The signature also predicted overall survival and metastasis-free survival. The signature’s robustness was demonstrated by the C-index (0.55–0.74) and the calibration plot in all nine cohorts and the 3-, 5-, and 8-year area under the receiver operating characteristic curve (0.67–0.77) in three cohorts. The nomogram analyses demonstrated CRPCPS’ clinical applicability. The CRPCPS thus appears useful for RFS prediction in PCa.

scholarly journals Establishment And Validation Of Coagulation Factor-based Nomogram For Predicting The Recurrence-free Survival Of Prostate Cancer

2021 ◽  
Author(s):  
Jialin Meng ◽  
Zichen Bian ◽  
Chenyu Zhu ◽  
Zhi Tao ◽  
Xiaoyan Jin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Coagulation Factor ◽  
Calibration Plot ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Coagulation Pathway

Abstract Background: We aimed to establish and validate a coagulation-feature-based nomogram to predict recurrence-free survival for prostate cancer patients.Methods: The study contained 168 prostate cancer patients who had received radical prostatectomy between 2012 and 2018. The Kaplan-Meier plot and log-rank analysis were used to screen recurrence-free survival-related features. The nomogram was established by combining the significant coagulation features with clinicopathological characteristics by using Cox regression analysis. The accuracy and clinical significance of the nomogram model were assessed by receiver operating characteristic (ROC) curve, Kaplan-Meier plot, and calibration plot. Besides, we explored the correlation between coagulation pathway activity and patients’ prognosis based on public datasets by using gene set variation analysis (GSVA) analysis.Results: The results suggested that patients in the high-risk subgroup showed unfavorable prognoses than those in the low-risk subgroup classified by the nomogram model in both the training (log-rank P < 0.0001) and validation (log-rank P = 0.0004) cohorts. The nomogram model exhibited high discriminative accuracy in the training cohort [1-year area under the curve (AUC) of 0.74, and 3-year AUC of 0.69], which was confirmed in the internal validation cohort (C-index = 0.651). Besides, the calibration plots confirmed good concordance for the prediction of recurrence-free survival at 1 and 3 years. Besides, the subgroup analyses confirmed the usage of this model in different clinicopathological subgroups. Finally, GSVA analyses suggested that patients with higher coagulation pathway scores mostly had unfavorable prognoses than those with lower scores, a result consistent with the findings obtained above.Conclusions: In conclusion, we develop a practical nomogram model for the recurrence-free survival predicting of prostate cancer patients. This model may offer clinicians prognostic assessments and facilitate personalized treatment.

Oncological outcomes in high-risk prostate cancer after radical prostatectomy based on Gleason score: USC experience with 3,755 cases.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 60-60
Author(s):  
Hooman Djaladat ◽  
Weichen Xu ◽  
Jie Cai ◽  
Gary Lieskovsky ◽  
Siamak Daneshmand
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Cox Regression ◽  
Adjuvant Radiation ◽  
Recurrence Free Survival ◽  
Clinical Recurrence ◽  
Free Survival ◽  
Oncological Outcomes

60 Background: Gleason score is an important predictor of oncological outcomes after radical prostatectomy. However, it remains unclear whether there is a difference in outcomes between Gleason score (GS) 8 and 9-10 disease. We compare oncological outcomes after open radical prostatectomy for prostate cancer patients with GS of 8 versus 9-10. Methods: Of 3,755 radical prostatectomy patients (1987-2008), 360 patients with final pathology of GS 8, 9 or 10 and N0M0 were included. No significant differences between age, race and surgical margins between the two groups. Impact of GS on outcomes was controlled for preoperative PSA, pathological stage, use of adjuvant radiation therapy and use of neoadjuvant/adjuvant hormone deprivation therapy in multivariable analyses. Outcomes of interest were biochemical recurrence free survival (BCRFS), clinical recurrence free survival (CRFS) and overall survival (OS). Kaplan Meier plots, log rank tests and multivariable Cox regression model were used to analyze the data. Results: Median follow-up for GS 8 and GS 9-10 were 10.0 years and 8.6 years, respectively (p=0.43). Conclusions: Long term follow up after radical prostatectomy reveals significant differences in BCRFS and CRFS but not OS between patients with GS 8 vs. 9-10 prostate cancers. Further studies may examine sub-stratification of GS 8 tumors into a lower risk category than GS 9-10 tumors. [Table: see text] [Table: see text]

scholarly journals Postoperative non-steroidal anti-inflammatory drug use and oncological outcomes of rectal cancer

BJS Open ◽  
2021 ◽  
Vol 5 (1) ◽  
Author(s):  
O Grahn ◽  
M Lundin ◽  
M-L Lydrup ◽  
E Angenete ◽  
M Rutegård
Keyword(s):  
Rectal Cancer ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Instrumental Variables ◽  
Cox Regression ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Oncological Outcomes ◽  
Anti Inflammatory ◽  
Instrumental Variables Approach

Abstract Background Non-steroidal anti-inflammatory drugs (NSAIDs) are known to suppress the inflammatory response after surgery and are often used for pain control. This study aimed to investigate NSAID use after radical surgical resection for rectal cancer and long-term oncological outcomes. Methods A cohort of patients who underwent anterior resection for rectal cancer between 2007 and 2013 in 15 hospitals in Sweden was investigated retrospectively. Data were obtained from the Swedish Colorectal Cancer Registry and medical records; follow-up was undertaken until July 2019. Patients who received NSAID treatment for at least 2 days after surgery were compared with controls who did not, and the primary outcome was recurrence-free survival. Cox regression modelling with confounder adjustment, propensity score matching, and an instrumental variables approach were used; missing data were handled by multiple imputation. Results The cohort included 1341 patients, 362 (27.0 per cent) of whom received NSAIDs after operation. In analyses using conventional regression and propensity score matching, there was no significant association between postoperative NSAID use and recurrence-free survival (adjusted hazard ratio (HR) 1.02, 0.79 to 1.33). The instrumental variables approach, including individual hospital as the instrumental variable and clinicopathological variables as co-variables, suggested a potential improvement in the NSAID group (HR 0.61, 0.38 to 0.99). Conclusion Conventional modelling did not demonstrate an association between postoperative NSAID use and recurrence-free survival in patients with rectal cancer, although an instrumental variables approach suggested a potential benefit.

Stage at presentation and oncologic outcomes for agent orange exposed and non-exposed United States veterans diagnosed with prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 259-259
Author(s):  
Alexander Tward ◽  
Jonathan David Tward
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Cox Regression ◽  
Smoking Status ◽  
Initial Therapy ◽  
Agent Orange ◽  
Oncologic Outcomes ◽  
Free Survival ◽  
Risk Of Death ◽  
Increased Risk

259 Background: Exposure of Vietnam War Veterans to the defoliant Agent Orange (AO) has been linked to increased tumor stage of Veterans diagnosed with prostate cancer. However, information on the effect of exposure to treatment outcomes is lacking. The goal of this study was to evaluate oncologic outcomes in Veterans based on AO exposure history, accounting for known prognostic covariates not previously studied. Methods: United States military Veterans diagnosed with prostate adenocarcinoma born between the years 1930-1956 were identified from a large professionally curated institutional database. Evaluable patients had to have known AO exposure status, age, NCCN risk group, Charlson comorbidity score, smoking status, and whether initial therapy was surgical, radiation, or systemic. Risk of death, metastasis, and progression stratified by the type of initial therapy received was analyzed using Cox regression. Results: There were 70 AO exposed and 561 non-exposed Veterans identified, with a median follow-up of 10.0 years. AO exposure Veterans (AOeV) were significantly younger (64.0 versus 65.7 years, p=0.013) at diagnosis and presented at more advanced stages (e.g. Stage 4: 14.3% versus 2.5%) than non-exposed Veterans (non-AOeV). There was no difference for overall survival (HR=0.86, p=0.576, metastasis-free survival (HR=1.5, p=0.212), or progression-free survival (HR=0.67, p 0.060) between AOeV versus non-AOeV in analyses stratified by treatment received accounting for other prognostic covariates. Cigarette smoking was associated with a 2- 3-fold increased risk of death over those who quit or never smoked. Conclusions: Although AOeV do present at younger age and higher clinical stages than non-AOeV, the oncologic outcomes after accounting for treatments received and other prognostic covariates are similar. The implication is that AOeV are more likely to be recommended multimodality or systemic therapies at presentation.

scholarly journals The impact of method of distal ureter management during radical nephroureterectomy on tumour recurrence

2014 ◽  
Vol 8 (11-12) ◽  
pp. 845 ◽  
Author(s):  
Anil Kapoor ◽  
Shawn Dason ◽  
Christopher B. Allard ◽  
Bobby Shayegan ◽  
Louis Lacombe ◽  
...  
Keyword(s):  
Cox Regression ◽  
Tumour Recurrence ◽  
Management Approach ◽  
Management Technique ◽  
Recurrence Free Survival ◽  
Radical Nephroureterectomy ◽  
Distal Ureter ◽  
Free Survival ◽  
Cox Regression Analysis

Introduction: Radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) must include some form of distal ureter management to avoid high rates of tumour recurrence. It is uncertain which distal ureter management technique has the best oncologic outcomes. To determine which distal ureter management technique resulted in the lowest tumour recurrence rate, we analyzed a multiinstitutional Canadian radical nephroureterectomy database.Methods: We retrospectively analyzed patients who underwent radical nephroureterectomy with distal ureter management for UTUC between January 1990 and June 2010 at 10 Canadian tertiary hospitals. Distal ureter management approaches were divided into 3 categories: (1) extravesical tenting for ureteric excision without cystotomy (EXTRAVESICAL); (2) open cystotomy with intravesical bladder cuff excision (INTRAVESICAL); and (3) extravesical excision with endoscopic management of ureteric orifice (ENDOSCOPIC). Data available for each patient included demographic details, distal ureter management approach, pathology and operative details, as well as the presence and location of local or distant recurrence. Clinical outcomes included overall recurrence-free survival and intravesical recurrence-free survival. Survival analysis was performed with the Kaplan-Meier method. Multivariable Cox regression analysis was also performed.Results: A total of 820 patients underwent radical nephroureterectomy with a specified distal ureter management approach at 10 Canadian academic institutions. The mean patient age was 69.6 years and the median follow-up was 24.6 months. Of the 820 patients, 406 (49.5%) underwent INTRAVESICAL, 316 (38.5%) underwent EXTRAVESICAL, and 98 (11.9%) underwent ENDOSOPIC distal ureter management. Groups differed significantly in their proportion of females, proportion of laparoscopic cases, presence of carcinoma in situ and pathological tumour stage (p < 0.05). Recurrence-free survival at 5 years was 46.3%, 35.6%, and 30.1% for INTRAVESICAL, EXTRAVESICAL and ENDOSCOPIC, respectively (p < 0.05). Multivariable Cox regression analysis confirmed that INTRAVESICAL resulted in a lower hazard of recurrence compared to EXTRAVESICAL and ENDOSCOPIC. When looking only at intravesical recurrence-free survival (iRFS), a similar trend held up with INTRAVESICAL having the highest iRFS, followed by ENDOSCOPIC and then EXTRAVESICAL management (p < 0.05). At last follow-up, 406 (49.5%) patients were alive and free of disease.Conclusion: Open intravesical excision of the distal ureter (INTRAVESICAL) during radical nephroureterectomy was associated with improved overall and intravesical recurrence-free survival compared with extravesical and endoscopic approaches. These findings suggest that INTRAVESICAL should be considered the gold standard oncologic approach to distal ureter management during radical nephroureterectomy. Limitations of this study include its retrospective design, heterogeneous cohort, and limited follow-up.

scholarly journals Identification and Validation of a Prognostic 5-Protein Signature for Biochemical Recurrence Following Radical Prostatectomy for Prostate Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Daojun Lv ◽  
Zanfeng Cao ◽  
Wenjie Li ◽  
Haige Zheng ◽  
Xiangkun Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Analysis ◽  
Biochemical Recurrence ◽  
Cox Regression ◽  
Characteristic Curve ◽  
The Cancer Genome Atlas ◽  
Medical Decision ◽  
Regression Analyses ◽  
Cox Regression Analysis ◽  
Protein Signature

Background: Biochemical recurrence (BCR) is an indicator of prostate cancer (PCa)-specific recurrence and mortality. However, there is a lack of an effective prediction model that can be used to predict prognosis and to determine the optimal method of treatment for patients with BCR. Hence, the aim of this study was to construct a protein-based nomogram that could predict BCR in PCa.Methods: Protein expression data of PCa patients was obtained from The Cancer Proteome Atlas (TCPA) database. Clinical data on the patients was downloaded from The Cancer Genome Atlas (TCGA) database. Lasso and Cox regression analyses were conducted to select the most significant prognostic proteins and formulate a protein signature that could predict BCR. Subsequently, Kaplan–Meier survival analysis and Cox regression analyses were conducted to evaluate the performance of the prognostic protein-based signature. Additionally, a nomogram was constructed using multivariate Cox regression analysis.Results: We constructed a 5-protein-based prognostic prediction signature that could be used to identify high-risk and low-risk groups of PCa patients. The survival analysis demonstrated that patients with a higher BCR showed significantly worse survival than those with a lower BCR (p &lt; 0.0001). The time-dependent receiver operating characteristic curve showed that the signature had an excellent prognostic efficiency for 1, 3, and 5-year BCR (area under curve in training set: 0.691, 0.797, 0.808 and 0.74, 0.739, 0.82 in the test set). Univariate and multivariate analyses indicated that this 5-protein signature could be used as independent prognosis marker for PCa patients. Moreover, the concordance index (C-index) confirmed the predictive value of this 5-protein signature in 3, 5, and 10-year BCR overall survival (C-index: 0.764, 95% confidence interval: 0.701–0.827). Finally, we constructed a nomogram to predict BCR of PCa.Conclusions: Our study identified a 5-protein-based signature and constructed a nomogram that could reliably predict BCR. The findings might be of paramount importance for the prediction of PCa prognosis and medical decision-making.Subjects: Bioinformatics, oncology, urology.

Obesity is a predictor in prostate cancer patients receiving prostatectomy after neoadjuvant hormonal therapy

2019 ◽  
Vol 106 (2) ◽  
pp. 133-138
Author(s):  
Lijiang Sun ◽  
Ting Xu ◽  
Xiaoliang Yuan ◽  
Feng Liu ◽  
Fengju Guan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hormonal Therapy ◽  
Roc Curve ◽  
Normal Weight ◽  
Castration Resistance ◽  
Free Survival ◽  
Positive Margins ◽  
Neoadjuvant Hormonal Therapy ◽  
Pathologic Features ◽  
Significant Difference

Objective: This study aimed to investigate the relationship between obesity and pathologic features and biochemical recurrence in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP) after neoadjuvant hormonal therapy (NHT). Methods: A total of 422 consecutive patients with clinically localized PCa who received NHT before RP were retrospectively analyzed. Unconditional multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) regarding probability. A receiver operating characteristic (ROC) curve was used to assess the efficacy of the predictive variables. Castration resistance free survival curves were obtained using the Kaplan-Meier method, and were compared using the log-rank test. Results: Being overweight was associated with an increased risk of positive margins (OR 2.281; 95% CI 1.292–4.028) after adjusting for potential confounders. The area under the ROC curve for overweight patients was larger than that for patients in the normal weight range. There was no significant difference between the overweight and normal weight groups regarding castration resistance free survival. Conclusions: Being overweight was associated with positive margins in patients with PCa undergoing RP after NHT.

scholarly journals Five lncRNAs Associated With Prostate Cancer Prognosis Identified by Coexpression Network Analysis

2020 ◽  
Vol 19 ◽  
pp. 153303382096357
Author(s):  
Xiaoyong Gong ◽  
Bobin Ning
Keyword(s):  
Prostate Cancer ◽  
Network Analysis ◽  
Cox Regression ◽  
Characteristic Curve ◽  
Interaction Network ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Normal Prostate ◽  
Cox Regression Analysis ◽  
Incidence And Mortality

Prostate cancer (PCa) is a highly malignant tumor, with increasing incidence and mortality rates worldwide. The aim of this study was to identify the prognostic lncRNAs and construct an lncRNA signature for PCa diagnosis by the interaction network between lncRNAs and protein-coding genes (PCGs). The differentially expressed lncRNAs (DElncRNAs) and PCGs (DEPCGs) between PCa and normal prostate tissues were screened from The Cancer Genome Atlas (TCGA) database. The DEPCGs were functionally annotated in terms of the enriched pathways. Weighted gene co-expression network analysis (WGCNA) of 104 PCa samples identified 15 co-expression modules, of which the Turquoise module was negatively correlated with cancer and included 5 key lncRNAs and 47 PCGs. KEGG pathway analyses of the core 47 PCGs showed significant enrichment in classic PCa-related pathways, and overlapped with the enriched pathways of the DEPCGs. LINC00857, LINC00900, LINC00908, LINC00900, SNHG3 and FENDRR were significantly associated with the survival of PCa and have not been reported previously. Finally, Multivariable Cox regression analysis was used to establish a prognostic risk formula, and the patients were accordingly stratified into the low- and high-risk groups. The latter had significantly worse OS compared to the low-risk group (P < 0.01), and the area under the receiver operating characteristic curve (ROC) of 14-year OS was 0.829. The accuracy of our prediction model was determined by calculating the corresponding concordance index (C-index) and risk curves. In conclusion, we established a 5-lncRNA prognostic signature that provides insights into the biological and clinical relevance of lncRNAs in PCa.

Sign in / Sign up

Export Citation Format

Share Document