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

2020 ◽  
Author(s):  
Tianwei Wang ◽  
Yunyan Wang

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.

2021 ◽  
Author(s):  
Pei-Min Hsieh ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Gin-Ho Lo ◽  
I-Cheng Lu ◽  
...  

Abstract Background: The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages.Methods: Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed.Results: In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0-96) months for the total cohort and was subdivided into 52 (8-96), 32 (1-96), 19 (0-84), and 12 (0-79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were 1) SR and cirrhosis; 2) SR, cirrhosis, and Child-Pugh (C-P) class; 3) SR, hepatitis B virus (HBV) infection, and C-P class; and 4) SR, HBV infection, and C-P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs non-SR were 44.0% vs 28.7%, 72.2% vs 42.6%, 42.6% vs 36.2, 44.6% vs 23.5%, and 41.4% vs 15.3% (all p-values<0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages.Conclusion: SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.


2021 ◽  
Author(s):  
Chao Zhang ◽  
Haixiao Wu ◽  
Guijun Xu ◽  
Wenjuan Ma ◽  
Lisha Qi ◽  
...  

Abstract Background: Osteosarcoma is the most common primary malignant bone tumor. The current study was conducted to describe the general condition of patients with primary osteosarcoma in a single cancer center in Tianjin, China and to investigate the associated factors in osteosarcoma patients with lung metastasis. Methods: From February 2009 to October 2020, patients from Tianjin Medical University Cancer Institute and Hospital, China were retrospectively analyzed. The Kaplan–Meier method was used to evaluate the overall survival of osteosarcoma patients. Prognostic factors of patients with osteosarcoma were identified by the Cox proportional hazard regression analysis. Risk factor of lung metastasis in osteosarcoma were investigated by the logistic regression model. Results: A total of 203 patients were involved and 150 patients were successfully followed up for survival status. The 5-year survival rate of osteo-sarcoma patients was 70.0%. Surgery, bone and lung metastasis were the significant prognostic factors in multivariable Cox regression analysis. Twenty-one (10.3%) patients showed lung metastasis at the diagnosis of osteosarcoma and 67 (33%) lung metastases during the later course. T3 stage (OR=11.415, 95%CI 1.362-95.677, P=0.025) and synchronous bone metastasis (OR=6.437, 95%CI 1.69-24.51, P=0.006) were risk factors of synchronous lung metastasis occurrence. Good necrosis (≥90%, OR=0.097, 95%CI 0.028-0.332, P=0.000) and elevated Ki-67 (≥50%, OR=4.529, 95%CI 1.241-16.524, P=0.022) were proved to be significantly associated with metachronous lung metastasis occurrence. Conclusion: The overall survival, prognostic factors and risk factors for lung metastasis in this single center provided insight about osteosarcoma management.


2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Huamei Tang ◽  
Lijuan Kan ◽  
Tong Ou ◽  
Dayang Chen ◽  
Xiaowen Dou ◽  
...  

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.


2020 ◽  
Author(s):  
Dong Han ◽  
Fei Gao ◽  
Nan Li ◽  
Hao Wang ◽  
Qi Fu

Abstract Background Lung large cell neuroendocrine carcinoma (L-LCNEC) has a poor prognosis with lower survival rate than other NSCLC patients. The estimation of an individual survival rate is puzzling. The main purpose of this study was to establish a more accurate model to predict the prognosis of L-LCNEC.Methods Patients aged 18 years or older with L-LCNEC were identified from the Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2015. Cox regression analysis was used to identify factors associated with survival time. The results were used to construct a nomogram to predict 1-year, and 3-year survival probability in L-LCNEC patients. Overall survival (OS) were compared between low risk group and high risk group by the Kaplan–Meier analysis.Results A total of 3216 patients were included in the study. We randomly divided all included patients into 7:3 training and validating groups. In multivariable analysis of training cohort, age at diagnosis, sex, stage of tumor, surgical treatment, radiotherapy and chemotherapy were independent prognostic factors for OS. All these factors were incorporated to construct a nomogram, which was tested in the validating cohort.Conclusions we constructed a visual nomogram prognosis model, which had the potential to predict the 1-year and 3-year survival rate of L-LCNEC patients, and could be used as an assistant prediction tool in clinical practice.


2021 ◽  
Vol 30 ◽  
pp. 096368972110550
Author(s):  
Jiarui Chen ◽  
Xingyu Liu ◽  
Qiuji Wu ◽  
Xueping Jiang ◽  
Zihang Zeng ◽  
...  

Chemokines exhibited complicated functions in antitumor immunity, with their expression profile and clinical importance of lung adenocarcinoma (LUAD) patients remaining largely undetermined. This study aimed to explore the expression patterns of chemokine family in LUAD and construct a predictive chemokine family-based signature. A total of 497 samples were downloaded from the Cancer Genome Atlas (TCGA) data portal as the training set, and the combination of 4 representative Gene Expression Omnibus (GEO) datasets, including GSE30219, GSE50081, GSE37745, and GSE31210, were utilized as the validation set. A three gene-based signature was constructed using univariate and stepwise multivariate Cox regression analysis, classifying patients into high and low risk groups according to the overall survival. The independent GEO datasets were utilized to validate this signature. Another multivariate analysis revealed that this signature remained an independent prognostic factor in LUAD patients. Furthermore, patients in the low risk group featured immunoactive tumor microenvironment (TME), higher IPS scores and lower TIDE scores, and was regarded as the potential beneficiaries of immunotherapy. Finally, the role of risky CCL20 was validated by immunohistochemistry (IHC), and patients possessed higher CCL20 expression presented shorter overall survival ( P = 0.011).


2021 ◽  
Author(s):  
Yushu Liu ◽  
Jiantao Gong ◽  
Yanyi Huang ◽  
Qunguang Jiang

Abstract Background:Colon cancer is a common malignant cancer with high incidence and poor prognosis. Cell senescence and apoptosis are important mechanisms of tumor occurrence and development, in which aging-related genes(ARGs) play an important role. This study aimed to establish a prognostic risk model based on ARGs for diagnosis and prognosis prediction of colon cancer .Methods: We downloaded transcriptome data and clinical information of colon cancer patients from the Cancer Genome Atlas(TCGA) database and the microarray dataset(GSE39582) from the Gene Expression Omnibus(GEO) database. Univariate COX, least absolute shrinkage and selection operator(LASSO) regression algorithm and multivariate COX regression analysis were used to construct a 6-ARG prognosis model and calculated the riskScore. The prognostic signatures is validated by internal validation cohort and external validation cohort(GSE39582).In addition, functional enrichment pathways and immune microenvironment of aging-related genes(ARGs) were also analyzed. We also analyzed the correlation between rsikScore and clinical features and constructed a nomogram based on riskScore. We are the first to construct prognostic nomogram based on ARGs.Results: Through univariate COX,LASSO regression algorithm and multivariate COX regression analysis,6 prognostic ARGs (PDPK1,RAD52,GSR,IL7,BDNF and SERPINE1) were screened out and riskScore was constructed. We have verified that riskScore has good prognostic value in both internal validation cohort and external validation cohort. Pathway enrichment and immunoanalysis of ARGs provide a direction for the treatment of colon cancer patients. We also found that riskScore was closely related to the clinical characteristics of patients. Based on riskScore and related clinical features, we constructed a nomogram, which has good predictive performance.Conclusion: The 6-ARG prognostic signature we constructed has a certain clinical predictive ability. Its riskScore is also closely related to clinical characteristics, and nomogram based on this has stronger predictive ability than a single indicator. ARGs and the nomogram we constructed may provide a promising treatment for colon cancer patients.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 266-266
Author(s):  
Carl Fredrik Warfvinge ◽  
Jacob Elebro ◽  
Margareta Heby ◽  
Bjorn Nodin ◽  
Jakob Eberhard ◽  
...  

266 Background: Periampullary cancers can be divided into different morphological subtypes where those having an intestinal-type (I-type) morphology have a better prognosis than those with a pancreatobiliary-type (PB-type) morphology. In recent years much focus of antineoplastic research has been directed towards the central role played by various subsets of T-lymphocytes. Yet, very little is known of their role in different subtypes of periampullary cancer. Therefore, the aim of this study was to analyze the density of CD8+ (cytotoxic) and FoxP3+ (regulatory) T-cells in periampullary cancer, with particular reference to their relationship with survival by morphological subtype. Methods: Immunohistochemical expression of CD8 and FoxP3-positive tumor-infiltrating lymphocytes (TILs) was analyzed in tissue microarrays with tumors from 175 consecutive cases of periampullary adenocarcinoma, 110 of PB-type and 65 of I-type morphology, treated with pancreaticoduodenectomy. Kaplan-Meier and univariable and multivariable Cox regression analysis, adjusted for age, T-stage, N-stage, grade, sex, invasion of blood vessels, lymphatic vessels, adjuvant chemotherapy and resection margins were applied to determine the impact of CD8 and FoxP3 expression on 5-year overall survival (OS). Results: In I-type tumors, a high density of CD8+ as well as FoxP3+ TILs was significantly associated with a prolonged overall survival (HR = 0.39, 95% CI 0.19-0.80 and HR = 0.32, 95% CI 0.15 –0.67). The association between high density of FoxP3+ TILs and survival remained significant in multivariable analysis (HR = 0.37, 95% CI 0.17-0.84) while the association between CD8+ TILs and survival did not. The density of CD8+ and FoxP3+ TILs was not prognostic in PB-type tumors. Conclusions: High density of CD8+ and FoxP3+ TILs correlates with a prolonged overall survival in I-type but not in PB-type periampullary adenocarcinomas. Thus, morphological subtype appears to be an important determinant of the prognostic and predictive impact of the inflammatory microenvironment in periampullary carcinoma, and should be considered in future studies.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 556-556
Author(s):  
Yaw A. Nyame ◽  
Kelsey K. Baker ◽  
Robert B. Montgomery ◽  
Petros Grivas ◽  
Mary Weber Redman ◽  
...  

556 Background: Disparities in bladder cancer outcomes exist by race/ethnicity and sex. However, limited data exists on differences in tumor biology by race/ethnicity and sex. Methods: This is a retrospective analysis of non-synonymous mutational data from the cBioPortal open access platform. A total of eight unique cohorts were identified. The cohort was divided into groups by sex and race. Somatic mutations were selected from those with frequency > 7% from TCGA and DNA damage repair (DDR) genes. Univariable analysis was performed using Student’s t-test and Fischer’s exact test. For those genes with significant differences, multivariate Cox regression analysis was performed, including a test for interaction for genes significantly associated with race or gender. Results: A total of 917 unique patients were identified from cBioPortal for this analysis. Median age for the cohort was 68 years (range: 25-98) and 227 (25%) were identified as female. The cohort was majority white (85%). TP53 (54% vs. 31%, p < 0.001), ARID1A (29% vs. 7%, p < 0.001), ERBB3 (12% vs. 3%, p = 0.01) and CDKN1A (8% vs 18%, p = 0.02) were differentially mutated in white tumors compared to non-white tumors. ERBB2 was more common among male (13%) compared to female (6%) patients in the cohort (p < 0.01). There were no differences in DDR genes by race/ethnicity and sex. The median age for those with ERCC2 (70.4 vs. 66.8 years) and RAD51 (76.3 vs. 67.0 years) mutations was higher compared to those without the mutations, respectively. On multivariable analysis, ERCC2 (HR 0.45, 95% CI 0.25, 080), SPTAN1 (HR 0.50, 95% CI 0.29, 0.84), and EP300 (HR 0.60, 95% CI 0.39, 0.92) were associated with survival. There was a significant interaction between white race and CDKN1A in the survival analysis, with non-white patients with CKDN1A mutations having increased hazard for mortality (HR 3.1, 95% CI 1.14, 8.42). Conclusions: Somatic mutational differences existed by both race and gender in a large cohort of patients with bladder cancer. These findings are limited by poor representation of non-white patients and retrospective design; advocating for representative patient cohorts to assess tumor biology in bladder cancer disparities research.


BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yusheng Huang ◽  
Zhiguo Liu ◽  
Limei Zhong ◽  
Yi Wen ◽  
Qixiang Ye ◽  
...  

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is a fatal malignancy owing to the lack of effective tools to predict overall survival (OS). MicroRNAs (miRNAs) play an important role in HNSCC occurrence, development, invasion and metastasis, significantly affecting the OS of patients. Thus, the construction of miRNA-based risk signatures and nomograms is desirable to predict the OS of patients with HNSCC. Accordingly, in the present study, miRNA sequencing data of 71 HNSCC and 13 normal samples downloaded from The Cancer Genome Atlas (TCGA) were screened to identify differentially expressed miRNAs (DEMs) between HNSCC patients and normal controls. Based on the exclusion criteria, the clinical information and miRNA sequencing data of 67 HNSCC samples were selected and used to establish a miRNA-based signature and a prognostic nomogram. Forty-three HNSCC samples were assigned to an internal validation cohort for verifying the credibility and accuracy of the primary cohort. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the functions of 11 miRNA target genes. Results In total, 11 DEMs were successfully identified. An 11-miRNA risk signature and a prognostic nomogram were constructed based on the expression levels of these 11 DEMs and clinical information. The signature and nomogram were further validated by calculating the C-index, area under the curve (AUC) in receiver-operating characteristic curve analysis, and calibration curves, which revealed their promising performance. The results of the internal validation cohort shown the reliable predictive accuracy both of the miRNA-based signature and the prognostic nomogram. GO and KEGG analyses revealed that a mass of signal pathways participated in HNSCC proliferation and metastasis. Conclusion Overall, we constructed an 11-miRNA-based signature and a prognostic nomogram with excellent accuracy for predicting the OS of patients with HNSCC.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuelong Wang ◽  
Bin Zhou ◽  
Yuxin Xia ◽  
Jianxin Zuo ◽  
Yanchao Liu ◽  
...  

Abstract Background DNA methylation alteration is frequently observed in Lung adenocarcinoma (LUAD) and may play important roles in carcinogenesis, diagnosis, and prognosis. Thus, this study aimed to construct a reliable methylation-based nomogram, guiding prognostic classification screening and personalized medicine for LUAD patients. Method The DNA methylation data, gene expression data and corresponding clinical information of lung adenocarcinoma samples were extracted from The Cancer Genome Atlas (TCGA) database. Differentially methylated sites (DMSs) and differentially expressed genes (DEGs) were obtained and then calculated correlation by pearson correlation coefficient. Functional enrichment analysis and Protein-protein interaction network were used to explore the biological roles of aberrant methylation genes. A prognostic risk score model was constructed using univariate Cox and LASSO analysis and was assessed in an independent cohort. A methylation-based nomogram that included the risk score and the clinical risk factors was developed, which was evaluated by concordance index and calibration curves. Result We identified a total of 1362 DMSs corresponding to 471 DEGs with significant negative correlation, including 752 hypermethylation sites and 610 hypomethylation sites. Univariate cox regression analysis showed that 59 DMSs were significantly associated with overall survival. Using LASSO method, we constructed a three-DMSs signature that was independent predictive of prognosis in the training cohort. Patients in high-risk group had a significant shorter overall survival than patients in low-risk group classified by three-DMSs signature (log-rank p = 1.9E-04). Multivariate cox regression analysis proved that the three-DMSs signature was an independent prognostic factor for LUAD in TCGA-LUAD cohort (HR = 2.29, 95%CI: 1.47–3.57, P = 2.36E-04) and GSE56044 cohort (HR = 2.16, 95%CI: 1.19–3.91, P = 0.011). Furthermore, a nomogram, combining the risk score with clinical risk factors, was developed with C-indexes of 0.71 and 0.70 in TCGA-LUAD and GSE56044 respectively. Conclusions The present study established a robust three-DMSs signature for the prediction of overall survival and further developed a nomogram that could be a clinically available guide for personalized treatment of LUAD patients.


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