scholarly journals The role of resistin gene polymorphisms in bladder cancer

2020 ◽  
Author(s):  
Shi Deng ◽  
Yin sheng He ◽  
pan zhao ◽  
Peng Zhang
Keyword(s):  
Risk Factors ◽  
Bladder Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Heterozygous Genotype ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Homozygous Genotype ◽  
Potential Biomarker ◽  
Normal Controls

Abstract Background: Published studies have demonstrated that resistin, a recently discovered adipokine, is connected to insulin resistance, type 2 diabetes mellitus, obesity, inflammation, and atherosclerotic vascular disease. A comprehensive study of the adipocytokine family and tumor pathogenesis indicates an intimate relationship between resistin and the incidence, progression, and metastasis of gastric cancer, esophageal cancer, choriocarcinoma, colorectal cancer, pancreatic cancer, and biliary tract cancer. To date, the connection between resistin and bladder cancer has not been thoroughly investigated and remains unclear. Methods: Overall, 322 patients with bladder cancer and 366 normal controls were included in the study. Two SNPs of the resistin gene, rs1862513 (also known as −420 C/G) and rs10401670 (3’UTR C/T) were genotyped across the entire cohort. Next, the association between the two SNPs and the incidence, risk factors, and prognosis of bladder cancer, were analyzed. Results: The frequency of T allele and CT/TT genotype of rs10401670 was significantly lower in bladder cancer patients (P=0.03, OR=0.79 and P = 0.018, OR = 0.68, respectively) compared to normal controls. No differences were found with regards to the rs1862513 genotype frequency and the distribution of allele frequency between the two groups. Stratified analyses showed that the CT heterozygous genotype of rs10401670 was associated with bladder cancer at an earlier age (OR=1.97, 95% CI=1.14–3.40) and the CG heterozygous genotype of rs1862513 was correlated with high incidence of bladder cancer in smokers (OR=1.73, 95 % CI=1.05–2.87). Multiple Cox regression analysis showed that for bladder cancer patients, the presence of a CG heterozygous genotype of rs1862513 was associated with a decrease in the risk of recurrence in MIBC patients (P = 0.04，OR= 0.49). Additionally, the rs1040167 CT/TT genotype (P = 0.03，OR= 2.45), especially the TT homozygous genotype (P = 0.02，OR= 3.00) was associated with high risk of death. These results indicate that the rs1040167 CT/TT and TT homozygous genotype may be a risk factor for overall survival of bladder cancer patients. Conclusions: Our results suggest that resistin genotype serves as a risk factors for the occurrence and prognosis of bladder cancer, and could be be a potential biomarker for this devastating disease.

Prognostic Nomogram Incorporating Immunohistochemical Results for the Overall Survival of Patients with Bladder Cancer.

2020 ◽  
Author(s):  
Tianwei Wang ◽  
Yunyan Wang
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Bladder Cancer ◽  
Risk Model ◽  
Cox Regression ◽  
Validation Cohort ◽  
Multivariable Analysis ◽  
Clinical Information ◽  
Internal Validation ◽  
Cox Regression Analysis

Abstract Objectives: In this study, we want to combine GATA3, VEGF, EGFR and Ki67 with clinical information to develop and validate a prognostic nomogram for bladder cancer.Methods: A total of 188 patients with clinical information and immunohistochemistry were enrolled in this study, from 1996 to 2018. Univariable and multivariable cox regression analysis was applied to identify risk factors for nomogram of overall survival (OS). The calibration of the nomogram was performed and the Area Under Curve (AUC) was calculated to assess the performance of the nomogram. Internal validation was performed with the validation cohort., the calibration curve and the AUC were calculated simultaneously.Results: Univariable and multivariable analysis showed that age (HR: 2.229; 95% CI: 1.162-4.274; P=0.016), histology (HR: 0.320; 95% CI: 0.136-0.751; P=0.009), GATA3 (HR: 0.348; 95% CI: 0.171-0.709; P=0.004), VEGF (HR: 2.295; 95% CI: 1.225-4.301; P=0.010) and grade (HR: 4.938; 95% CI: 1.339-18.207; P=0.016) remained as independent risk factors for OS. The age, histology, grade, GATA3 and VEGF were included to build the nomogram. The accuracy of the risk model was further verified with the C-index. The C-index were 0.65 (95% CI, 0.58-0.72) and 0.58 (95% CI, 0.46-0.70) in the training and validation cohort respectively. Conclusions: A combination of clinical variables with immunohistochemical results based nomogram would predict the overall survival of patients with bladder cancer.

scholarly journals Development of a novel prognostic signature for predicting the overall survival of bladder cancer patients

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Huamei Tang ◽  
Lijuan Kan ◽  
Tong Ou ◽  
Dayang Chen ◽  
Xiaowen Dou ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Overall Survival ◽  
Bladder Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Test Group ◽  
Training Group ◽  
The Cancer Genome Atlas ◽  
Methylation Site ◽  
Cox Regression Analysis

Abstract Background: Bladder cancer is one of the most common malignancies. So far, no effective biomarker for bladder cancer prognosis has been identified. Aberrant DNA methylation is frequently observed in the bladder cancer and holds considerable promise as a biomarker for predicting the overall survival (OS) of patients. Materials and methods: We downloaded the DNA methylation and transcriptome data for bladder cancer from The Cancer Genome Atlas (TCGA), a public database, screened hypo-methylated and up-regulated genes, similarly, hyper-methylation with low expression genes, then retrieved the relevant methylation sites. Cox regression analysis was used to identify a nine-methylation site signature of a training group. Predictive ability was validated in a test group by receiver operating characteristic (ROC) analysis. Results: We identified nine bladder cancer-specific methylation sites as potential prognostic biomarkers and established a risk score system based on the methylation site signature to evaluate the OS. The performance of the signature was accurate, with area under curve was 0.73 in the training group and 0.71 in the test group. Taking clinical features into consideration, we constructed a nomogram consisting of the nine-methylation site signature and patients’ clinical variables, and found that the signature was an independent risk factor. Conclusions: Overall, the significant nine methylation sites could be novel prediction biomarkers, which could aid in treatment and also predict the overall survival likelihoods of bladder cancer patients.

scholarly journals Sepsis-associated Encephalopathy In ICU Admissions: Prevalence, Early Risk of Death, and its Early Prevent and Control

2020 ◽  
Author(s):  
Dao-Ming Tong ◽  
Shao-Dan Wang ◽  
Yuan-Wei Wang ◽  
Ying Wang ◽  
Yuan-Yuan Gu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Critically Ill ◽  
Cox Regression ◽  
Abdominal Cavity ◽  
Early Prevention ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Early Risk ◽  
Early Risk Factors ◽  
And Control

Abstract Background: Sepsis-associated encephalopathy (SAE) is a common encephalopathy in ICU. We are to definite whether SAE present an high prevalence rate and early risk factors for death in ICU 48 hours, while to cognize its important of early prevention/ control.Methods: We retrospectively enrolled patients with acute critically ill from ICU (January, 2015 to January, 2017). All patients were selected from onset to ICU ≤3 hours. The prevalence and some early risk factors of death in SAE was estimated by using a continuous head and thorax /abdominal cavity CT scans. Results: 748 critically ill adults were analyzed. The prevalence of sepsis within initial 48 hours was 40.4% (302/748). The median time from infection to sepsis was 9 hours ( range, 1-48 ). The SAE (93.4%, 282/302) was diagnosed in sepsis patients, and most of them (96.8%) presented multiple organ dysfunction syndromes (MODS). While the fatality of SAE was in 32.0% at initial 48 hours and 69.1% at initial 14 days. Cox regression analysis, unused antibiotic within initial 3 hours (OR, 0.39; 95% CI, 0.22-0.89), severe inflammatory storm (OR, 0.70; 95% CI, 0.58- 0.94), lower GCS (OR, 2.7; 95% CI, 1.5-3.6), and MODS (OR, 0.37; 95% CI, 0.26-0.96) were early risk factors for death in SAE. Early risk factors for predicting SAE were related to severe inflammatory storm (OR, 3.10; 95% CI, 2.28-4.33), MODS (OR, 3.57; 95% CI, 2.73- 4.67), and unused antibiotics within initial 3 hours (OR, 0.25; 95% CI, 0.11-0.56).Conclusions: SAE in ICU is an high prevalent acute brain dysfunction and most with MODS. The early bad prognosis in SAE was related to the failure of early prevention and control.

Chemoradiation-related lymphopenia and its association with survival in patients with anal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 3-3
Author(s):  
Grace Lee ◽  
Daniel W. Kim ◽  
Vinayak Muralidhar ◽  
Devarati Mitra ◽  
Nora Horick ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Anal Cancer ◽  
Cox Regression ◽  
Cox Model ◽  
Rank Test ◽  
Anal Squamous Cell Carcinoma ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Kaplan Meier ◽  
Increased Risk

3 Background: While treatment-related lymphopenia (TRL) is common and associated with poorer survival in multiple solid malignancies, little data exists for anal cancer. We evaluated TRL and its association with survival in anal cancer patients treated with chemoradiation (CRT). Methods: A retrospective analysis of 140 patients with non-metastatic anal squamous cell carcinoma (SCC) treated with definitive CRT was performed. Total lymphocyte counts (TLC) at baseline and monthly intervals up to 12 months after initiating CRT were analyzed. Multivariable Cox regression analysis was performed to evaluate the association between overall survival (OS) and TRL, dichotomized by G4 TRL ( < 0.2k/μl) two months after initiating CRT. Kaplan-Meier and log-rank tests were used to compare OS between patients with versus without G4 TRL. Results: Median time of follow-up was 55 months. Prior to CRT, 95% of patients had a normal TLC ( > 1k/μl). Two months after initiating CRT, there was a median of 71% reduction in TLC from baseline and 84% of patients had TRL: 11% G1, 31% G2, 34% G3, and 8% G4. On multivariable Cox model, G4 TRL at two months was associated with a 3.7-fold increased risk of death (p = 0.013). On log-rank test, the 5-year OS rate was shorter in the cohort with versus without G4 TRL at two months (32% vs. 86%, p < 0.001). Conclusions: TRL is common and may be another prognostic marker of OS in anal cancer patients treated with CRT. The association between TRL and OS supports the hypothesis that host immunity plays an important role in survival among patients with anal cancer. These results support ongoing efforts of randomized trials underway to evaluate the potential role of immunotherapy in localized anal cancer.

scholarly journals Development and validation of Pyroptosis‑related lncRNAs prediction model for bladder cancer

2022 ◽  
Author(s):  
Thongher Lia ◽  
Yanxiang Shao ◽  
Parbatraj Regmi ◽  
Xiang Li
Keyword(s):  
Bladder Cancer ◽  
Regression Analysis ◽  
Cancer Patients ◽  
Risk Score ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis

Bladder cancer is one of the highly heterogeneous disorders accompanied by a poor prognosis. This study aimed to construct a model based on pyroptosis‑related lncRNA to evaluate the potential prognostic application in bladder cancer. The mRNA expression profiles of bladder cancer patients and corresponding clinical data were downloaded from the public database from The Cancer Genome Atlas (TCGA). Pyroptosis‑related lncRNAs were identified by utilizing a co-expression network of Pyroptosis‑related genes and lncRNAs. The lncRNA was further screened by univariate Cox regression analysis. Finally, 8 pyroptosis-related lncRNA markers were established using Lasso regression and multivariate Cox regression analysis. Patients were separated into high and low-risk groups based on the performance value of the median risk score. Patients in the high-risk group had significantly poorer overall survival (OS) than those in the low-risk group (p &lt; 0.001), and In multivariate Cox regression analysis, the risk score was an independent predictive factor of OS ( HR&gt;1, P&lt;0.01). The area under the curve (AUC) of the 3- and 5-year OS in the receiver operating characteristic (ROC) curve were 0.742 and 0.739 respectively. In conclusion, these 8 pyroptosis-related lncRNA and their markers may be potential molecular markers and therapeutic targets for bladder cancer patients.

scholarly journals А New Combination of Prognostic Markers in Follicular Lymphoma That Influences the Choice of Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4520-4520
Author(s):  
Ekaterina S. Nesterova ◽  
Nataliya A. Severina ◽  
Bella V. Biderman ◽  
Andrey B. Sudarikov ◽  
Tatiana N. Obukhova ◽  
...  
Keyword(s):  
Risk Factors ◽  
Regression Analysis ◽  
Follicular Lymphoma ◽  
Tumor Size ◽  
Cox Regression ◽  
Proliferation Index ◽  
Ki 67 ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Probability Of Death

Abstract Background: Follicular lymphoma (FL) is characterized by clinical and morphological heterogeneity. It is based on the pathogenetic mechanisms of the development of tumor cells. The identification and assessment of risk factors associated with the course of the disease and treatment outcome in FL is an important task, as it allows to evaluate and predict the effectiveness of therapy. Objective: Identify and estimate risk factors for overall survival (OS) and progression free survival (PFS) in FL. Patients and Methods: The prospective exploratory study conducted at National Research Center for Hematology (Moscow) from 01/2017 to 04/2021 included patients (pts)(in total, 80) with FL. Morpho-immunohistochemical, cytogenetic and molecular studies were performed on biopsies of lymph nodes taken before the start of therapy. The mutational status of exon 16 and intron polymorphism rs_2072407 of the EZH2 gene were investigated by Sanger sequencing. 18q21/BCL-2 rearrangements were determined by conventional cytogenetic analysis and/or FISH study. The results obtained in a blind study were compared with the effect of the therapy. Results: Of the 80 pts 34 were male: Me (median) age 50 years (range 30-72) and 46 were female: Me 56 (range 21-81). The median follow-up (FU) time was 53 months. As a result of the study in the multivariate Cox regression model (likelihood-ratio test, p=0.01) of significant factors, selected in the previously univariate analysis, the following statistically significant (Wald test) risk factors for OS and PFS (the events: progression, relapse, or death) were obtained: • BCL-2 gene rearrangements (no vs yes) • EZH2 gene genotypes (AA/AG vs GG) • proliferation index Ki-67 (&gt;35%) • morphological grade (3А vs 1/2) • tumor size (&gt;6 cm /bulky/) (Tab. 1, Fig. 1) The BCL-2 rearrangements were found in 45 from 80 pts (56%; 95 % CI 45-66). The probability of BCL-2 rearrangements is estimated to be about 0.5 (50%). According to the results of Cox-regression analysis (by OS) in the absence of BCL-2 rearrangements, the risk of death in FL was generally significantly (p = 0.01) higher than in the group with its presence: HR = 4.3 (95 % CI 1.5-13.0) (Fig. 2) Mutations in the 16th exon of the EZH2 gene (mutEZH2) were found in 10/80 (13%) pts. Analysis of EZH2 gene mutations with BCL-2 rearrangements revealed that in the mutEZH2 group with the presence of BCL-2 rearrangements, the number of deaths associated with progression is significantly less than in the control initial groups (mutEZH2 with BCL-2 rearrangements - 0/6, mutEZH2 without BCL-2 rearrangements - 2/4, wEZH2 with BCL-2 rearrangements - 3/39 (8%), wEZH2 without BCL-2 rearrangements - 11/31 (35%)) . The prognostic significance of EZH2 genotypes in lymphomas was studied for the first time in this study. The frequencies of rs_2072407 genotypes were: AA - 24% (19), AG - 42% (34), and GG - 34% (27). AA and AG genotypes of the EZH2 gene in pts with FL were associated with an increased risk of death (compared to the GG genotype) : HR = 2.9 (95% CI: 1.2-10.6), p = 0.01 (Fig. 3). The GG variant in most cases was associated with wEZH2 (26/27 (96%)) with BCL-2 rearrangements (16/26 (62%)) and a favorable prognosis (26/27 (96%)) (p = 0.01). Index of proliferative activity Ki-67&gt; 35% (n = 40) and Ki-67 ≤ 35% (n = 40) were equally common in the study group. With a Ki-67&gt; 35%, the probability of death is 2.9 (95% CI 1.1-9.7) times higher. The frequency distribution of morphological grade was as follows: grade 3A - 53% (n = 43) and grade 1-2 - 47% (n = 37). At grade 3A, the probability of death is 2.5 (95% CI 1.1-7.8) times higher. The number of pts with tumor size &gt;6 cm (bulky) and ≤ 6 cm in the sample is approximately the same (41 and 39, respectively), the presence of bulky increased the mortality risk by 2.1 (95% CI 1.0-6.5) times. A short time from the manifestation of the disease to appeal to medical care is a predictor of poor prognosis, but this result we received earlier on a large sample of pts was not significant on a smaller sample. Conclusions: As a result of the multivariable Cox regression analysis, we identified and confirmed the previously obtained factors (bulky, grade 3A, Ki-67 &gt; 35%, short medical history), and discovered new biogenetic factors (BCL-2 rearrangements and the GG rs2072407 genotype of the EZH2 gene). The model based on these independent risk factors improves the accuracy of predicting adverse events and allows to use more personalized treatment options for patients with FL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The timing from perioperative chemotherapy and disease recurrence could have clinical impact on survival in bladder cancer patients treated with salvage chemotherapy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 444-444
Author(s):  
Eiji Kikuchi ◽  
Nozomi Hayakawa ◽  
Koichirou Ogihara ◽  
Minami Omura ◽  
Ryuichi Mizuno ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Cancer Patients ◽  
Radical Cystectomy ◽  
Cox Regression ◽  
Prognostic Indicator ◽  
Disease Recurrence ◽  
Salvage Chemotherapy ◽  
Perioperative Chemotherapy ◽  
Cox Regression Analysis

444 Background: Our aim was to clarify whether the duration between perioperative chemotherapy and disease recurrence could affect therapeutic efficacy of salvage chemotherapy in bladder cancer patients treated with radical cystectomy. Methods: We retrospectively identified 201 patients treated with radical cystectomy and perioperative chemotherapy of neoadjuvant chemotherapy (NAC) and/or adjuvant chemotherapy (AC) for bladder cancer at our 7 institutions between 2003 and 2015. Of them 56 patients received salvage chemotherapy for disease recurrence and were included in the present analysis. We classified these patients according to the time from perioperative chemotherapy received to disease recurrence ( < 12 months, 12-24 months, and 24 < months) and compared their clinical characteristics and survival outcomes. Results: Overall, 33, 14, and 9 patients developed disease recurrence in < 12 months, 12-24 months, and < 24 months, respectively after perioperative chemotherapy. Patients in the 12-24 months group had a higher smoking rate compared to those in the other two groups, and were higher rate of female in comparison to the < 24 months group. Twenty-four (42.8%) patients received NAC alone, 23 (41.1%) received AC alone, and 9 (16.1%) received both NAC and AC. Twenty-two (66.7%), 9 (64%), and 4 (44.4%) patients received NAC in the < 12 months group, the 12-24 months group, and the < 24 months group, respectively. Furthermore, 19 (57.6%), 7 (50%), and 6 (66.7%) patients received AC in the < 12 months group, the 12-24 months group, and the < 24 months group, respectively. The 5 year overall survival in the < 12 months group was 26.6%, which was significantly lower than those in the 12-24 months group (51.1%, p < 0.001) and in the 24 months group (46.9%, p = 0.014). Multivariate Cox regression analysis revealed that disease recurrence after perioperative chemotherapy within 12 months was the only independent prognostic indicator for overall death (p = 0.032). Conclusions: Bladder cancer patients with disease recurrence within 12 months from their perioperative chemotherapy have a worse overall survival after salvage chemotherapy.

scholarly journals Mannose Receptor as a Potential Biomarker for Gastric Cancer: A Pilot Study

2017 ◽  
Vol 32 (3) ◽  
pp. 278-283 ◽  
Author(s):  
Deng-Rui Liu ◽  
Quan-Lin Guan ◽  
Ming-Tai Gao ◽  
Lei Jiang ◽  
Hong-Xia Kang
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Mannose Receptor ◽  
Receptor Expression ◽  
High Expression ◽  
Cox Regression Analysis ◽  
Potential Biomarker ◽  
High Mannose ◽  
Gastric Cancer Patients

Background The mannose receptor is an immune adhesion molecule mainly expressed on the surface of antigen-presenting cells such as nonmature dendritic cells and macrophages. This study aimed to investigate mannose receptor expression and its predictive role in papillary gastric cancer patients. Methods The expression of the mannose receptor was measured in 120 samples of gastric cancer tissues and corresponding paracarcinoma tissues, by immunohistochemical and quantitative real-time PCR analysis. The relationships between mannose receptor expression and clinicopathological features of gastric cancer patients were analyzed. Results The expression rate of the mannose receptor in gastric cancer cells was 45.8% (54/120), significantly higher than that in the paracarcinoma tissue (20.0%, 36/120) (χ2 = 6.286, p = 0.012). High expression of the mannose receptor was closely related to tumor size, T stage, N stage and Union for International Cancer Control (UICC) stage of gastric cancer (p<0.05). A Kaplan-Meier survival model indicated that the survival of patients in the high-expression mannose receptor group was significantly shorter than in the low-expression mannose receptor group (p<0.05). Cox regression analysis showed that high mannose receptor expression was an independent predictor for the prognosis of patients with gastric cancer. Conclusions High mannose receptor expression indicates poor prognosis for gastric cancer patients. The mannose receptor may be an important molecular marker for gastric cancer prognosis.

scholarly journals Association of Perioperative Cell-free DNA (cfDNA) Concentrations with Risk of Recurrence in Patients with Breast Cancer

2021 ◽  
Author(s):  
Fara Hassan ◽  
Jiang Huai Wang ◽  
Carolyn Cullinane ◽  
Michael Ita ◽  
Mark Corrigan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Perioperative Period ◽  
Breast Cancer Patients ◽  
Cell Free Dna ◽  
Cox Regression Analysis ◽  
Free Dna ◽  
Post Operative Period ◽  
Potential Biomarker

Abstract Background: Circulating cell-free DNA (cfDNA) is a potential biomarker of disease status in cancer patients and provides valuable diagnostic and prognostic information in breast cancer. In this study, we sought to quantify the cfDNA concentrations in the perioperative period and to investigate its prognostic relevance in breast cancer patients.Methods: Sixty-three (n=63) breast cancer patients undergoing curative surgery were screened for inclusion. Blood samples were collected: pre-operatively (Pre-op), post-operatively (POD) within weeks 1-2, weeks 3-4 and weeks 5-12 following surgery. cfDNA was extracted and quantified using nanodrop spectrophotometer. All patients were followed up for 5 years.Results: The median age was 52(26-84) years. During the perioperative period, patients with high cfDNA concentrations(cutoff:480ng/ml) had inferior recurrence free survival (RFS) than those with lower cfDNA concentrations (pre-operative period: median RFS: 30(3-60) months versus 60(6-60) months (p<0.0001), post-operative period: median RFS: 24(3-60) months versus 60(6-60) months (p<0.0001). Multivariate Cox regression analysis showed that post op cfDNA concentration (p=0.017), subtypes (p=0.011) and tumour size (p=0.006) were negative prognostic factor for RFS in the pre-operative period and post-operative period.Conclusion: Our study demonstrated the prognostic ability of perioperative cfDNA concentrations in breast cancer patients. Further, prospective studies are warranted to validate its clinical utility in breast cancer.

scholarly journals Identification of an 11-Autophagy-Related-Gene Signature as Promising Prognostic Biomarker for Bladder Cancer Patients

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 375
Author(s):  
Chaoting Zhou ◽  
Alex Heng Li ◽  
Shan Liu ◽  
Hong Sun
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Regression Analysis ◽  
Cancer Patients ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Related Gene ◽  
Training Cohort ◽  
Cox Regression Analysis ◽  
Therapeutic Decisions

Background: Survival rates for highly invasive bladder cancer (BC) patients have been very low, with a 5-year survival rate of 6%. Accurate prediction of tumor progression and survival is important for diagnosis and therapeutic decisions for BC patients. Our study aims to develop an autophagy-related-gene (ARG) signature that helps to predict the survival of BC patients. Methods: RNA-seq data of 403 BC patients were retrieved from The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) database. Univariate Cox regression analysis was performed to identify overall survival (OS)-related ARGs. The Lasso Cox regression model was applied to establish an ARG signature in the TCGA training cohort (N = 203). The performance of the 11-gene ARG signature was further evaluated in a training cohort and an independent validation cohort (N = 200) using Kaplan-Meier OS curve analysis, receiver operating characteristic (ROC) analysis, as well as univariate and multivariate Cox regression analysis. Results: Our study identified an 11-gene ARG signature that is significantly associated with OS, including APOL1, ATG4B, BAG1, CASP3, DRAM1, ITGA3, KLHL24, P4HB, PRKCD, ULK2, and WDR45. The ARGs-derived high-risk bladder cancer patients exhibited significantly poor OS in both training and validation cohorts. The prognostic model showed good predictive efficacy, with the area under the ROC curve (AUCs) for 1-year, 3-year, and 5-year overall survival of 0.702 (0.695), 0.744 (0.640), and 0.794 (0.658) in the training and validation cohorts, respectively. A prognostic nomogram, which included the ARGs-derived risk factor, age and stage for eventual clinical translation, was established. Conclusion: We identified a novel ARG signature for risk-stratification and robust prediction of overall survival for BC patients.

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