scholarly journals Prognostic value of Ki-67 in patients with hypertension and prostate cancer: A real-world study in a Chinese population

2020 ◽  
Author(s):  
Zhijun Cao ◽  
Mengqi Xiang ◽  
Zhiyu Zhang ◽  
Jianglei Zhang ◽  
Minjun Jiang ◽  
...  

Abstract Background Prostate cancer is the second most common malignancy in males worldwide, with high mortality, especially when combined with hypertension. Ki-67 is one of the most reliable markers of growth for neoplastic human cell populations. However, the prognostic value of Ki-67 in patients with hypertension and prostate cancer remains unclear.Methods We retrospectively analyzed 296 patients with hypertension and prostate cancer from May 1, 2012, to October 1, 2015. The overall survival was evaluated by Cox regression models and Kaplan-Meier analysis. In addition, a nomogram was established, and the accuracy of the model was assessed by a calibration curve.Results A total of 101 (34.1%) patients died. In the multivariate analysis, being Ki-67(+) was associated with a >5-fold increase in the risk of death (hazard ratio [HR] 5.83, 95% confidence interval [CI] 3.35-10.14, p<0.001) and a 2-fold increase in the risk of progression (HR 2.06, 95% CI 1.37-3.10, p<0.001). Multivariate Lasso regression showed that smoking, heart failure, ACS, Ki-67 expression, serum albumin, prognostic nutritional index, surgery, Gealson score, and stage were positively associated with prognosis in patients with prostate cancer. To quantify the contribution of each covariate to the prognosis, a nomogram of the Cox model was generated. The nomogram demonstrated excellent accuracy in estimating the risk of death, with a bootstrap-corrected C index of 0.829. There was also a suitable calibration curve for risk estimation.Conclusions The presence of Ki-67 predicts worsened outcomes for overall mortality. A cross-validated multivariate score including Ki-67 had excellent concordance and efficacy for predicting prostate cancer.

2019 ◽  
Author(s):  
Zhijun Cao ◽  
Mengqi Xiang ◽  
Zhiyu Zhang ◽  
Jianglei Zhang ◽  
Minjun Jiang ◽  
...  

Abstract Purpose Prostate cancer is the second most common malignancy with high mortality among males around the world, especially combine with hypertension. Ki-67 is one of the most reliable markers for growth fraction of neoplastic human cell populations. However, the prognostic value and prediction of Ki-67 in patients with hypertension and prostate cancer remain unclear. Materials and methods We launched a retrospective analysis of 296 patients with hypertension and prostate cancer from May 1, 2012, to Oct 1, 2015. The overall survival was evaluated using Cox regression models and Kaplan-Meier analysis. A nomogram was established. The accuracy of the model was assessed by calibration curve. Results Multivariate analysis showed that the Ki-67 (+) class was associated with an over 5-fold increase in the risk of death (HR 5.83, 95% CI 3.35-10.14, p<0.001) and a 2-fold increase in the risk of progression (HR 2.06, 95% CI 1.37-3.10, p<0.001). Multivariate Lasso regression showed that smoking, heart failure, ACS, Ki-67 expression, serum albumin, prognostic nutritional index, surgery, Gealson score, and stage were positively associated with prognosis in patients with prostate cancer. To quantify the contribution of each covariate to the prognosis, a nomogram of the Cox model was generated and displayed. The nomogram demonstrated excellent accuracy in estimating the risk of death, with a bootstrap-corrected C index of 0.829. There was also a suitable calibration curve for risk estimation.Conclusions Ki-67(+) predicts worsened outcomes of OM. A cross-validated multivariate score, including Ki-67(+), showed excellent concordance and efficacy of predicting prostate cancer.


2021 ◽  
pp. postgradmedj-2021-139981
Author(s):  
Shimin Tang ◽  
Hao Jiang ◽  
Zhijun Cao ◽  
Qiang Zhou

IntroductionProstate cancer is a common malignancy in men that is difficult to treat and carries a high risk of death. miR-219-5p is expressed in reduced amounts in many malignancies. However, the prognostic value of miR-219-5p for patients with prostate cancer remains unclear.MethodsWe retrospectively analysed data from 213 prostate cancer patients from 10 June 2012 to 9 May 2015. Overall survival was assessed by Kaplan-Meier analysis and Cox regression models. Besides, a prediction model was constructed, and calibration curves evaluated the model’s accuracy.ResultsOf the 213 patients, a total of 72 (33.8%) died and the median survival time was 60.0 months. We found by multifactorial analysis that miR-219-5p deficiency increased the risk of death by nearly fourfold (HR: 3.86, 95% CI): 2.01 to 7.44, p<0.001) and the risk of progression by twofold (HR: 2.79, 95% CI: 1.68 to 4.64, p<0.001). To quantify each covariate’s weight on prognosis, we screened variables by cox model to construct a predictive model. The Nomogram showed excellent accuracy in estimating death’s risk, with a corrected C-index of 0.778.ConclusionsmiR-219-5p can be used as a biomarker to predict death risk in prostate cancer patients. The mortality risk prediction model constructed based on miR-219-5p has good consistency and validity in assessing patient prognosis.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Milani ◽  
G Cavenaghi ◽  
L Obici ◽  
R Mussinelli ◽  
C Klersy ◽  
...  

Abstract Background Skeletal scintigraphy with bone tracers is a key tool for cardiac ATTR diagnosis. However its prognostic value has not been systematically assessed. Purpose We evaluated the prognostic relevance of a quantitative method to assess regional 99mTc-DPD uptake by SPECT in the heart of ATTRwt patients. Methods All ATTRwt patients (n=229) undergoing clinical assessment and bone scintigraphy at our center (from 2012 to 2019) were enrolled. Theyreceived approximately 700 MBq of 99mTc-DPD. Planar whole body acquisition 10' after the injection followed by cardiac SPECT after 3 hours were performed. SPECT data were reconstructed into 64x64 matrices with an ordered-subset expectation maximization algorithm. For each wall region and for the apex, a circular region of interest (ROI, 20 pixels) was manually drawn and a value equating to the number of counts contained in the ROI was obtained. Partial correlation of ln-transformed ROI and biomarkers was retrieved from a multivariable regression model, while controlling for each cardiac wall region. Multivariable Cox regression was used to assess the prognostic role of lnROI while adjusting for wall region, NT-proBNP, cTnI and eGFR. Hazard ratios and 95% confidence intervals (HR, 95% CI) were computed. The Harrell's c statistic was reported for model discrimination. The interaction of biomarker and regional wall on survival was assessed; also, to account for intra-subject correlation of measures, within subject robust standard errors were computed. Results Median follow-up was 21 months (IQR 11, 40) and 39 (17%) patients died. Median age was 76 years (IQR, 72–80), NT-proBNP 2944 ng/L (IQR, 1815–5319), cTnI 0.095 ng/L (IQR, 0.062–0.144) and eGFR 62 mL/min (IQR, 51–77). ROI did not correlate with any of NT-proBNP, eGFR, age, cTnI or mLVWT (R&lt;1% in all cases). All analyses were adjusted for cardiac wall. At the multivariable Cox regression (Harrell's c=0.75), there was a linear increase in the risk of death associated with lnROI (HR 2.14, P=0.014), which was independent of cardiac wall region, NTproBNP, cTnI and eGFR. Only cTnI maintained a significant prognostic value. The association of lnROI and mortality was not modified by the site of measurement test for interaction with cardiac wall p=0.818). At the predefined subgroup analysis, the risk of death was similar for all walls; we computed the optimal cut-off for 12 months survival at the apex (a region usually lately involved) to 4193 (AUC: 0.68, sensitivity 80%, specificity 68%). At the multivariable Cox regression (Harrell's c 0.76), apex ROI&gt;4193 was an independent predictor of death (HR 3.60, 95% CI 1.45–8.93, p=0.006) and outperformed all the biomarkers tested. Conclusions Quantitative assessment of ROI uptake at cardiac SPECT is a powerful predictor of survival in ATTRwt patients, independent of and outperforming the other known prognostic factors. This observation warrants validation with prolonged follow-up and in independent patient series. Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 259-259
Author(s):  
Alexander Tward ◽  
Jonathan David Tward

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.


2011 ◽  
Vol 18 (3) ◽  
pp. 113-119
Author(s):  
Daimantas MILONAS ◽  
Giedrė SMAILYTĖ ◽  
Darius TRUMBECKAS ◽  
Mindaugas JIEVALTAS

Background. The aim of the study was to present the oncologic outcomes and to determine the prognostic factors of overall (OS) and cancer-specific survival (CSS) as well as disease-progression-free survival (DPFS) after surgery for pT3b prostate cancer. Materials and methods. In 2002–2007, a pT3b stage after radical prostatectomy was detected in 56 patients. Patients were divided into groups according to the prostate-specific antigen (PSA) level (20 ng/ml), lymph nodes status (N0 vs. Nx vs. N1) and the Gleason score (6–7 vs. 8–10). The Kaplan–Meier analysis was used to calculate OS, CSS and DPFS. The Cox regression was used to identify the predictive factors of survival. Results. Five-year OS, CSS and DPFS rates were 75.1%, 79.6% and 79.3%, respectively. The survival was significantly different when comparing the Gleason 6–7 and 8–10 groups. The 5-year OS, CSS and DPFS were 91.2% vs. 48.6%, 97.1% vs. 51.1% and 93.8 vs. 51.1%, respectively. There was no difference in survival among the groups with a different PSA level. The OS and CSS but not DPFS were significantly different when comparing the N0 and N1 groups. The 5-year OS and CSS was 84.4% vs. 37.5% and 87.3% vs. 47.6%, respectively. The specimen Gleason score was a significant predictor of OS and CSS. The risk of death increased up to 4-fold when a Gleason score 8–10 was present at the final pathology. Conclusions. Radical prostatectomy may offer acceptable CSS, DPFS and OS rates in pT3b PCa. However, outcomes in patients with N1 and specimen Gleason ≥8 were significantly worse, suggesting the need of multimodality treatment in such cases. Keywords: prostate cancer, locally advanced, surgery, outcome


2021 ◽  
Vol 8 ◽  
Author(s):  
Yuxiang Fan ◽  
Xinyu Peng ◽  
Yubo Wang ◽  
Baoqin Li ◽  
Gang Zhao

Background: The histone deacetylase (HDAC) family limited accessibility to chromatin containing tumor suppressor genes by removing acetyl groups, which was deemed a path for tumorigenesis. Considering glioma remained one of the most common brain cancers with a dichotomy prognosis and limited therapy responses, HDAC inhibitors were an area of intensive research. However, the expression profiles and prognostic value of the HDACs required more elucidation.Methods: Multiple biomedical databases were incorporated, including ONCOMINE, GEPIA, TCGA, CGGA, GEO, TIMER, cBioPortal, and Metascape, to study expression profiles, prognostic value, immune infiltration, mutation status, and enrichment of HDACs in glioma. STRING and GeneMANIA databases were used to identify HDAC1-related molecules. LASSO regression, Cox regression, Kaplan-Meier plot, and receiver operating characteristic (ROC) analyses were performed for HDAC1-related signature construction and validation.Results:HDAC1 was significantly overexpressed in glioma, while HDAC11 was downregulated in glioblastoma. Except for HDAC 6/9/10, the HDAC family expression was significantly associated with glioma grade. Most of the HDAC family also correlated with glioma genetic mutations. Higher HDAC1 expression level predicted more dismal overall survival (OS) (p &lt; 0.0001) and disease-free survival (DFS) (p &lt; 0.0001), but a higher level of HDAC11 held more favorable OS (p = 2.1e−14) and DFS (p = 4.8e−08). HDAC4 displayed the highest mutation ratio, at 2.6% of the family. The prognostic value of HDAC1 was validated with ROC achieving 0.70, 0.77, 0.75, and 0.80 as separability for 1-, 3-, 5-, and 10-years OS predictions in glioma, respectively. Moreover, HDAC1 expression positively correlated with neutrophil (r = 0.60, p = 2.88e-47) and CD4+ T cell infiltration (r = 0.52, p = 3.96e-35) in lower-grade glioma. The final HDAC1-related signature comprised of FKBP3, HDAC1 (Hazard Ratio:1.49, 95%Confidence Interval:1.20–1.86), PHF21A, RUNX1T1, and RBL1, and was verified by survival analysis (p &lt; 0.0001) and ROC with 0.80, 0.84, 0.83, and 0.88 as separability for 1-, 3-, 5-, and 10-years OS predictions, respectively. The signature was enriched in chromatin binding.Conclusion: HDAC family was of clinical significance for glioma. Most of the HDAC family significantly correlated with the glioma grade, IDH1 mutation, and 1p/19q codeletion. HDAC1 was both a prognostic and immune infiltration indicator and a central component of the HDAC1-related signature for precise prognosis prediction in glioma.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Hu Qian ◽  
Ting Lei ◽  
Pengfei Lei ◽  
Yihe Hu

While the prognostic value of autophagy-related genes (ARGs) in OS patients remains scarcely known, increasing evidence is indicating that autophagy is closely associated with the development and progression of osteosarcoma (OS). Therefore, we explored the prognostic value of ARGs in OS patients and illuminate associated mechanisms in this study. When the OS patients in the training/validation cohort were stratified into high- and low-risk groups according to the risk model established using least absolute shrinkage and selection operator (LASSO) regression analysis, we observed that patients in the low-risk group possessed better prognosis ( P < 0.0001 ). Univariate/Multivariate COX regression and subgroup analysis demonstrated that the ARGs-based risk model was an independent survival indicator for OS patients. The nomogram incorporating the risk model and clinical features exhibited excellent prognostic accuracy. GO, KEGG, and GSVA analyses collectively indicated that bone development-associated pathway mediated the contribution of ARGs to the malignance of OS. Immune infiltration analysis suggested the potential pivotal role of macrophage in OS. In summary, the risk model based on 12 ARGs possessed potent capacity in predicting the prognosis of OS patients. Our work may assist clinicians to map out more reasonable treatment strategies and facilitate individual-targeted therapy in osteosarcoma.


2019 ◽  
Vol 17 (2) ◽  
pp. 161-168 ◽  
Author(s):  
Yvonne H. Sada ◽  
Brandon G. Smaglo ◽  
Joy C. Tan ◽  
Hop S. Tran Cao ◽  
Benjamin L. Musher ◽  
...  

Background: Pathologically positive lymph nodes (ypN+) after preoperative chemotherapy are associated with poor survival in patients with gastric cancer. Little is known about the association between response to preoperative therapy and the benefit of postoperative therapy. Methods: This retrospective cohort study of the National Cancer Database included patients with clinically node-positive (cN+) gastric cancer treated with preoperative therapy followed by surgery (2006–2014). Preoperative treatment modality was categorized as the inclusion of radiation therapy (RT) or chemotherapy alone. Pretreatment clinical and pathologic stages were used to determine pathologic treatment response rates. The association between overall risk of death and preoperative treatment, disease response, and adjuvant therapy use was evaluated using multivariable Cox regression. Results: Preoperative RT was used in 53.6% of 1,976 patients with cN+ gastric cancer, (74.3% cardia and 10.1% noncardia). The nodal response rate was 38.9% and was higher with RT than with chemotherapy alone (cardia, 46.0% vs 29.1%; P<.001; noncardia, 43.8% vs 31.9%; P=.06). Preoperative RT was associated with an approximate 2-fold increase in the odds of pathologic response compared with chemotherapy. Overall, use of adjuvant therapy was not associated with a decreased risk of death. A primary tumor response with residual nodal disease was not associated with survival (hazard ratio [HR], 1.03; 95% CI, 0.66–1.60). However, a nodal response with residual primary disease was significantly associated with survival (HR, 0.54; 95% CI, 0.44–0.65). Conclusions: More than one-third of node-positive gastric cancers showed pathologic nodal response with preoperative treatment. RT is associated with a higher response than chemotherapy. Patients with ypN+ disease have worse survival, regardless of whether they receive postoperative therapy. Future gastric cancer trials should evaluate the role of preoperative RT and individualize postoperative therapy use.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15594-15594
Author(s):  
A. Banu ◽  
E. Banu ◽  
D. Dionysopoulos ◽  
J. Medioni ◽  
F. Scotte ◽  
...  

15594 Background: Clinical studies suggested that the extent of neuro-endocrine differentiation in prostate cancer increases with tumor progression and the development of androgen refractory status. Chromogranine (CgA) and neuron-specific enolase (NSE) are currently explored as surrogate markers. Methods: Eligible chemonaive HRPC patients (pts) were required to have an ECOG performance status (PS) ≤ 2. Before chemotherapy initiation, we quantified NSE, CgA and PSA in the venous blood using commercial kits. We evaluated the impact of baseline NSE, CgA and PSA on overall survival (OS) using multivariate Cox regression analysis, stratified by chemotherapy regimen. Secondary, we studied the correlation between NSE, CgA, PSA and other important variables as age, Gleason score, hemoglobin, number of metastatic sites and ECOG PS. Results: Data of 39 consecutive HRPC pts treated between December 01–06 in a single French center were analyzed. Chemotherapy was docetaxel-based in 92% of pts. Median age was 71 years (range 51–86) and 79% of pts had bone metastases. Elevated NSE, CgA and PSA were observed in 6, 9 and 30% of pts and median levels were 10.8, 67 and 23.3 ng/mL, respectively. Gleason 8–10 was present in 49% of pts. Significant correlations were observed between NSE and the number of metastatic sites and between CgA and age, hemoglobin and ECOG PS. The baseline PSA was only correlated with Gleason score. Median OS for the entire cohort was 24.4 months (95% CI, 18.8–29.9). Two-year OS was 15% and only 19% of patients are dead. Univariate Cox regression analysis showed only a significant relationship between OS and baseline NSE: hazard ratio= 1.09 (95% CI, 1.03–1.16), P=0.006. No other known prognostic factors are related to outcome. A multivariate model including baseline NSE, CgA, ECOG PS and Gleason score showed a 15% rise of the risk of death related to NSE (borderline P value). Conclusions: NSE was the most powerful predictor of survival for HRPC pts. Our results emphasize the theory that cells secreting NSE are chemoresistant, with a negative impact on OS. No significant financial relationships to disclose.


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