scholarly journals Bioinformatics Analysis of Apolipoprotein H Demonstrates Its Potential as a Prognostic Biomarker in Kidney Renal Clear Cell Carcinoma

Author(s):  
Peng Wang ◽  
Guan-an Zhao

Abstract Objectives This study aimed to systematically reveal the clinical value of APOH in KIRC.Methods The expression of APOH and its methylation level in KIRC were explored. Also, the prognostic value of APOH was evaluated. In addition, the correlation of APOH and immune infiltrates in KIRC was analyzed. Finally, enrichment analysis was performed to predict the APOH-associated pathways in KIRC.Results Compared with the normal group, APOH was down-regulated in KIRC both in mRNA and protein levels. The APOH expression was related to several phenotypes of KIRC patients. Kaplan-Meier analysis showed that APOH high expression correlated with shorter OS, PFI, and DSS time. Cox regression only indicated the independent prognostic impact of APOH for PFI. ROC curve showed the better prediction performance of APOH for PFI and nomogram further revealed its contribution to survival probability. Additionally, a negative correlation between APOH expression and methylation was observed, and APOH methylation did not influence the prognosis of patients. In addition, both expression and methylation of APOH were related to immune infiltrates, suggesting the importance of immune infiltrates in KIRC. Finally, the KEGG and GSEA analyses indicated a positive relationship of APOH with Complement and coagulation cascades pathways in KIRC.Conclusions APOH was closely related to the prognosis of KIRC patients and might be involved in the Complement and coagulation cascades pathway, implying the involvement of APOH in tumorigenesis and metastasis of KIRC.

2021 ◽  
Vol 20 ◽  
pp. 153303382110362
Author(s):  
Chujie Chen ◽  
Yiyu Sheng

Kidney renal clear cell carcinoma (KIRC) is one of the most malignant diseases with poor survival rate over the world. The tumor microenvironment (TME) is highly related to the oncogenesis, development, and prognosis of KIRC. Thus, making the identification of KIRC biomarkers and immune infiltrates critically important. Microtubule Interacting and Trafficking Domain containing 1(MITD1) was reported to participate in cytokinesis of cell division. In the present study, multiple bioinformatics tools and databases were applied to investigate the expression level and clinical value of MITD1 in KIRC. We found that the expression of MITD1 was significantly increased in KIRC tissues. Further, the KIRC patients with high MITD1 levels showed a worse overall survival (OS) rate and disease free survival (DFS) rate. Otherwise, we found a significant correlation MITD1 expression and the abundance of CD8+ T cells. Functional enrichment analyses revealed that immune response and cytokine-cytokine receptor are very critical signaling pathways which associated with MITD1 in KIRC. In conclusion, our findings indicated that MITD1 may be a potential biomarker and associated with immune infiltration in KIRC.


2021 ◽  
Author(s):  
Huy Gia Vuong ◽  
Hieu Trong Le ◽  
Tam N.M. Ngo ◽  
Kar-Ming Fung ◽  
James D. Battiste ◽  
...  

Abstract Introduction: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients.Methods: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS).Result: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR = 1.446; 95% CI = 1.143-1.829) whereas ACVR1 (HR = 0.712; 95% CI = 0.518-0.976) and FGFR1 mutations (HR = 0.408; 95% CI = 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR = 0.620; 95% CI = 0.386-0.996). Adjusted for age, gender, tumor location, and the extent of resection, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors.Conclusions: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. It could help neuro-oncologists better evaluate the risk stratification of patients and consider pertinent treatments.


2021 ◽  
Vol 12 ◽  
Author(s):  
Chunxia Zhao ◽  
Yulu Wang ◽  
Famei Tu ◽  
Shuai Zhao ◽  
Xiaoying Ye ◽  
...  

BackgroundSome studies have proven that autophagy and lncRNA play important roles in AML. Several autophagy related lncRNA signatures have been shown to affect the survival of patients in some other cancers. However, the role of autophagy related lncRNA in AML has not been explored yet. Hence, this study aims to find an autophagy related lncRNA signature that can affect survival for AML patients.MethodA Pearson correlation analysis, a Kaplan–Meier survival curve, a univariate cox regression, and a multivariate cox regression were performed to establish an autophagy related lncRNA signature. A univariate cox regression, a multivariate cox regression, a Kaplan–Meier survival curve, and a ROC curve were applied to confirm if the signature is an independent prognosis for AML patients. The relationship between the signature and the clinical features was explored by using a T test. Gene Set Enrichment Analysis (GSEA) was used to investigate the potential tumor related pathways.ResultsA four-autophagy related lncRNA (MIR133A1HG, AL359715.1, MIRLET7BHG, and AL356752.1) signature was established. The high risk score based on signature was related to the short survival time of AML patients. The signature was an independent factor for the prognosis for AML patients (HR = 1.684, 95% CI = 1.324–2.142, P < 0.001). The signature was correlated with age, leukocyte numbers, and FAB (M3 or non-M3). The P53, IL6/JAK/STAT3, TNF-α, INF-γ, and IL2/STAT5 pathways might contribute to the differences between the risk groups based on signature in AML.ConclusionThe four autophagy related lncRNAs and their signature might be novel biomarkers for predicting the survival of AML patients. Some biological pathways might be the potential mechanisms of the signature for the survival of AML patients.


Author(s):  
Bo Xiao ◽  
Liyan Liu ◽  
Zhuoyuan Chen ◽  
Aoyu Li ◽  
Pingxiao Wang ◽  
...  

Melanoma is the most common cancer of the skin, associated with a worse prognosis and distant metastasis. Epithelial–mesenchymal transition (EMT) is a reversible cellular biological process that plays significant roles in diverse tumor functions, and it is modulated by specific genes and transcription factors. The relevance of EMT-related lncRNAs in melanoma has not been determined. Therefore, RNA expression data and clinical features were collected from the TCGA database (N = 447). Melanoma samples were randomly assigned into the training (315) and testing sets (132). An EMT-related lncRNA signature was constructed via comprehensive analyses of lncRNA expression level and corresponding clinical data. The Kaplan-Meier analysis showed significant differences in overall survival in patients with melanoma in the low and high-risk groups in two sets. Receiver operating characteristic (ROC) curves were used to measure the performance of the model. Cox regression analysis indicated that the risk score was an independent prognostic factor in two sets. Besides, a nomogram was constructed based on the independent variables. Gene Set Enrichment Analysis (GSEA) was applied to evaluate the potential biological functions in the two risk groups. Furthermore, the melanoma microenvironment was evaluated using ESTIMATE and CIBERSORT algorithms in the risk groups. This study indicates that EMT-related lncRNAs can function as potential independent prognostic biomarkers for melanoma survival.


2018 ◽  
Vol 28 (3) ◽  
pp. 586-593 ◽  
Author(s):  
Mette Calundann Noer ◽  
Sofie Leisby Antonsen ◽  
Bent Ottesen ◽  
Ib Jarle Christensen ◽  
Claus Høgdall

ObjectiveTwo distinct types of endometrial carcinoma (EC) with different etiology, tumor characteristics, and prognosis are recognized. We investigated if the prognostic impact of comorbidity varies between these 2 types of EC. Furthermore, we studied if the recently developed ovarian cancer comorbidity index (OCCI) is useful for prediction of survival in EC.Materials and MethodsThis nationwide register-based cohort study was based on data from 6487 EC patients diagnosed in Denmark between 2005 and 2015. Patients were assigned a comorbidity index score according to the Charlson comorbidity index (CCI) and the OCCI. Kaplan-Meier survival statistics and adjusted multivariate Cox regression analyses were used to investigate the differential association between comorbidity and overall survival in types I and II EC.ResultsThe distribution of comorbidities varied between the 2 EC types. A consistent association between increasing levels of comorbidity and poorer survival was observed for both types. Cox regression analyses revealed a significant interaction between cancer stage and comorbidity indicating that the impact of comorbidity varied with stage. In contrast, the interaction between comorbidity and EC type was not significant. Both the CCI and the OCCI were useful measurements of comorbidity, but the CCI was the strongest predictor in this patient population.ConclusionsComorbidity is an important prognostic factor in type I as well as in type II EC although the overall prognosis differs significantly between the 2 types of EC. The prognostic impact of comorbidity varies with stage but not with type of EC.


2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338
Author(s):  
Fabian Haak ◽  
Isabelle Obrecht ◽  
Nadia Tosti ◽  
Benjamin Weixler ◽  
Robert Mechera ◽  
...  

Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.


2020 ◽  
Vol 14 (18) ◽  
pp. 1733-1745
Author(s):  
Tian-Jun Zhao ◽  
Qian-Kun Yang ◽  
Chun-Yu Tan ◽  
Li-Dan Bi ◽  
Jie Li ◽  
...  

Aim: To evaluate the clinical value of plasma D-dimer/fibrinogen ratio (DFR) in patients hospitalized for heart failure (HF). Methods: Clinical data of 235 patients were retrospectively analyzed. Kaplan–Meier method and Cox regression analysis were used to identify significant prognosticators. Results: The Kaplan–Meier analysis showed that a higher DFR level was significantly associated with an increase in the end point outcomes, including HF readmission, thrombotic events and death (log-rank test: p < 0.001). The multivariate Cox regression analysis showed that the high tertile of DFR was significantly associated with the study end points (HR: 2.18; 95% CI: 1.31–3.62; p = 0.003), compared with the low tertile. Conclusion: DFR is a reliable prognostic indicator for patients hospitalized for HF.


2020 ◽  
Vol 19 ◽  
pp. 153303382097754
Author(s):  
Rongchang Zhao ◽  
Dan Ding ◽  
Wenyan Yu ◽  
Chunrong Zhu ◽  
Yan Ding

Background: As a common pathological type of lung cancer, lung adenocarcinoma (LUAD) is mainly treated by surgery, chemotherapy, targeted therapy and radiotherapy. Although a relatively mature treatment system has been established, there are few studies on the microenvironment of LUAD. Material and Methods: The immune and stromal scores of patients from the LUAD cohort in the TCGA database were obtained by using ESTIMATE. The relationship of immune and stromal scores with the clinicopathological characteristics and overall survival of LUAD patients was assessed by R. GO, KEGG and Cox regression analyses were employed to analyze intersecting genes and to identify reliable prognostic markers. The identified genes were also analyzed in the GEPIA database to assess their correlations with survival, and these relationships were verified with the Kaplan-Meier Plotter database. Results: The immune score was related to the survival time and tumor topography of LUAD patients. There was a significant correlation between stromal score and tumor metastasis. Through multivariate analysis, stage (HR = 1.640, 95% CI = 1.019-2.642, P = 0.042) and risk score (HR = 1.036, 95% CI = 1.026-1.046, P < 0.001). The genes (ARHGAP15, BTLA, CASS4, CLECL1, FAM129C, STAP1, TESPA1, and S100P) showed credible prognostic value in LUAD patients in TCGA through GEPIA database online analysis and verification in the Kaplan-Meier plotter database. Conclusions: In the microenvironment of lung adenocarcinoma, the differentially expressed genes screened by immune score and stromal score have certain value in evaluating the survival/prognosis of patients, as well as the invasion and progression of tumors.


2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Sirui Ma ◽  
Soumon Rudra ◽  
Jian L Campian ◽  
Sonika Dahiya ◽  
Gavin P Dunn ◽  
...  

Abstract Background We aimed to evaluate the clinical outcomes of molecular glioblastoma (mGBM) as compared to histological GBM (hGBM) and to determine the prognostic impact of TERT mutation, EGFR amplification, and CDKN2A/B deletion on isocitrate dehydrogenase (IDH)-wildtype GBM. Methods IDH-wildtype GBM patients treated with radiation therapy (RT) between 2012 and 2019 were retrospectively analyzed. mGBM was defined as grade II-III IDH-wildtype astrocytoma without histological features of GBM but with one of the following molecular alterations: TERT mutation, EGFR amplification, or combination of whole chromosome 7 gain and whole chromosome 10 loss. Overall survival (OS) and progression-free survival (PFS) were calculated from RT and analyzed using the Kaplan–Meier method. Multivariable analysis (MVA) was performed using Cox regression to identify independent predictors of OS and PFS. Results Of the 367 eligible patients, the median follow-up was 11.7 months. mGBM and hGBM did not have significantly different OS (median: 16.6 vs 13.5 months, respectively, P = .16), nor PFS (median: 11.7 vs 7.3 months, respectively, P = .08). However, mGBM was associated with better OS (hazard ratio [HR] 0.50, 95% CI 0.29–0.88) and PFS (HR 0.43, 95% CI 0.26–0.72) than hGBM after adjusting for known prognostic factors on MVA. CDKN2A/B deletion was associated with worse OS (HR 1.57, 95% CI 1.003–2.46) and PFS (HR 1.57, 95% CI 1.04–2.36) on MVA, but TERT mutation and EGFR amplification were not. Conclusion Criteria for mGBM may require further refinement and validation. CDKN2A/B deletion, but not TERT mutation or EGFR amplification, may be an independent prognostic biomarker for IDH-wildtype GBM patients.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3550-3550
Author(s):  
Karsten Schulmann ◽  
Sven Koepnick ◽  
Christoph Engel ◽  
Christiane Bernhardt ◽  
Verena Steinke ◽  
...  

3550 Background: Previous studies showed conflicting results regarding the value of ACT in MSI-H CC. A recent study reported differential benefits from 5-FU-based ACT comparing suspected sporadic vs suspected hereditary MSI-H CC. We sought to evaluate the prognostic impact of ACT in a large cohort of Lynch syndrome (LS) patients (pts) with stage II CC. Methods: To minimize selection bias diagnoses >2 years prior to registration in the database of the German HNPCC consortium were excluded. 278 patients (61% male, mean age 42.9y, 13% stage IIB, 51% with MMR gene mutation) were eligible. Overall Survival (OS), CC-specific Survival (CSS), and Disease Free Survival (DFS) were analyzed using Kaplan-Meier and Cox Regression analyses. Results: 5y OS, CSS and DFS were 95%, 95% and 93% respectively. Right-sided CC was independently associated with lower DFS in stage II and IIA. Increasing age was associated with lower OS, CSS and DFS in stage IIA, however we observed only trends in the multivariate analysis. Surgery alone (without ACT) was associated with a slightly lower OS in stage IIA (univariate HR 3,659; 95% CI 0,81-16,5; P=0.092); but not with lower DFS and CSS. Prognosis was not different comparing FOLFOX vs. 5-FU-based ACT. Conclusions: Our data suggest that LS pts with stage II CC do not benefit from ACT. FOLFOX was not superior to 5-FU-based ACT. If our results are confirmed, LS pts with stage IIA CC should not receive ACT. The group of stage IIB CC was too small to make definite conclusions. [Table: see text]


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