A pan-cancer analysis based on weighted gene co-expression network analysis identifies the biomarker utility of lamin B1 in human tumors

2021 ◽  
pp. 1-17
Author(s):  
Youwei Hua ◽  
Zhihui He ◽  
Xu Zhang
Keyword(s):  
Network Analysis ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Lamin B1 ◽  
Cancer Genome Atlas ◽  
Mrna Binding ◽  
Functional Mechanisms ◽  
Pan Cancer

Emerging evidence has revealed a relationship between lamin B1 (LMNB1) and several cancers such as cervical cancer, liver cancer, and prostate cancer. But no systematic pan-cancer analysis is available. Little is known about the clinical significance and biomarker utility of LMNB1. In this study, we first revealed the key role of LMNB1 in esophageal carcinoma (ESCA) through weighted gene co-expression network analysis (WGCNA) and disease-free survival (DFS) analysis. Based on this result and the datasets of the cancer genome atlas (TCGA), we explored the biomarker utility of LMNB1 across thirty-three tumors. We found that LMNB1 was highly expressed in most of the cancers and significant associations existed between LMNB1 expression and prognosis of cases of nearly half of the cancers. We also found that LMNB1 expression was associated with the infiltration level of Macrophages M1 and T cells CD4 memory activated in some cancers. Moreover, LMNB1 was mainly involved in the functional mechanisms of MRNA binding, olfactory transduction, and gene silencing. Our study first provides a pan-cancer study of LMNB1, thereby offering a relatively comprehensive understanding of the biomarker utility of LMNB1 across thirty-three tumors.

High preoperative levels of circulating SFRP5 predict better prognosis in colorectal cancer patients

2020 ◽  
Vol 16 (31) ◽  
pp. 2499-2509
Author(s):  
Chandra Kirana ◽  
Eric Smith ◽  
Doan T Ngo ◽  
Markus I Trochsler ◽  
Peter J Hewett ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Value ◽  
Disease Free Survival ◽  
Normal Mucosa ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Cancer Genome Atlas ◽  
Colorectal Cancer Patients ◽  
Diagnostic And Prognostic Value

The purpose of this research was to investigate the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC). We evaluated preoperative cSFRP5 levels in CRC patients and controls (n = 208). We found significantly higher cSFRP5 levels in CRC patients compared with non-CRC controls (p < 0.001). Levels of cSFRP5 were significantly lower in CRC patients with either vascular invasion (p = 0.001) or liver metastasis (p = 0.016). High cSFRP5 levels were associated with longer disease-free survival in both univariate (p = 0.024) and multivariate (p = 0.015) analyses. Analysis of an independent tissue cohort from The Cancer Genome Atlas database revealed significantly lower SFRP5 RNA expression in CRC tumor tissue compared with adjacent normal mucosa (n = 590 vs 47; p < 0.0001). Our findings confirm the role of cSFRP5 as a physiologic tumor suppressor and demonstrate its potential diagnostic and prognostic value in CRC.

scholarly journals Prognostic and Immunological Role of Gasdermin E in Pan-Cancer Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Zheng Zhang ◽  
Shuangshuang Zhao ◽  
Haizhen Yang ◽  
Yanwei Chen ◽  
Huahui Feng ◽  
...  
Keyword(s):  
The Cancer Genome Atlas ◽  
Survival Prognosis ◽  
Cancer Management ◽  
Cancer Associated Fibroblast ◽  
Cancer Genome Atlas ◽  
Cancer Types ◽  
Functional Mechanisms ◽  
Pan Cancer

Despite accumulating cell- or animal-based experiments providing the relationship between Gasdermin E (GSDME) and human diseases, especially in malignant cancers, no pan-cancer analysis about the function of GSMDE in cancer management can be available up to date. Our research, for the first time, explored the potential carcinogenic role of GSDME across 33 tumors from the public platform of TCGA (The cancer genome atlas) database. GSDME is highly expressed in most malignant cancers, and obvious relationship exists between GSDME level and survival prognosis of cancer patients. The expression of GSDME was statically associated with the cancer-associated fibroblast infiltration in diverse cancer types, such as BLCA, CHOL, GBM, KIRC, LIHC, MESO, STAD, and UCEC. Furthermore, pyroptosis, sensory perception of sound, and defense response to bacterium were involved in the functional mechanisms of GSDME expression from GO analysis. Last but not the least, in vitro experiments were also performed to identify GSDME-induced pyroptosis. Our first pan-cancer analysis of GSDME not only broadens the understanding of the carcinogenic roles of GSDME but also provides a promising therapeutic strategy for benefiting an increasing number of cancerous patients based on GSDME-induced pyroptosis.

Lamin B1 promotes tumor progression and metastasis in primary prostate cancer patients

2020 ◽  
Author(s):  
Fei Luo ◽  
Jiaxi Han ◽  
Yatong Chen ◽  
Kuo Yang ◽  
Zhihua Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Progression ◽  
Cancer Metastasis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Lamin B1 ◽  
Kaplan Meier ◽  
Primary Prostate Cancer ◽  
Clinical Relationship

Aims: To determine the role of lamin B1 (LMNB1) in the progression and metastasis of primary prostate cancer (PC). Patients & methods: Two PC cohorts were used to investigate the clinical relationship between LMNB1 expression and tumor progression and metastasis. Results: The qRT-PCR results revealed that LMNB1 expression was markedly increased in patients with aggressive features and was associated with worse prognosis. Logistic regression analyses indicated that LMNB1 expression is an independent risk factor for distant metastasis. Kaplan–Meier analysis showed that increased LMNB1 levels were related to poor disease-free survival in the primary PC cohort. Conclusion: This study reveals that upregulation of LMNB1 is associated with cancer metastasis and poor survival outcomes in primary PC patients.

scholarly journals Krüppel-Like Factor 7 is a Marker of Aggressive Gastric Cancer and Poor Prognosis

2017 ◽  
Vol 43 (3) ◽  
pp. 1090-1099 ◽  
Author(s):  
Zhonghua Jiang ◽  
Tingting Yu ◽  
Zhining Fan ◽  
Hongmei Yang ◽  
Xin Lin
Keyword(s):  
Gastric Cancer ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Strong Negative Correlation ◽  
Functional Studies ◽  
Expression Of Genes ◽  
Cancer Genome Atlas

Background/Aims: Krüppel-like factor (KLF) 7 protein is a member of the KLF transcription factor family, which plays important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation and metabolism. However, the role of KLF7 in gastric cancer (GC) is unknown. The aim of this study is to explore the role of KLF7 in GC and its correlation with clinicopathological characteristics and prognosis of GC patients. Methods: We first systematically evaluated dysregulation of the KLF family in The Cancer Genome Atlas (TCGA) GC database. Then, 252 patients who underwent surgery for GC were enrolled to validate the results from the TCGA. Functional studies were also used to explore the role of KLF7 in GC. Results: In the TCGA database, we found that KLF7 was an independent predictor for survival by both univariate and multivariate analysis (P<0.05). In a validation cohort, KLF7 expression was significantly increased in GC tissues compared with adjacent normal controls (P=0.013). High KLF7 expression correlated with inferior prognostic factors, such as T stage (P=0.022), N stage (P =0.005) and lymphovascular invasion (P=0.009). Furthermore, we observed a strong negative correlation between KLF7 expression and 5-year overall survival and disease-free survival in GC patients (P<0.05). Moreover, our in vitro studies showed a notable decrease in migration in KLF7 knockdown cells. Conclusion: KLF7 has an important role in GC progression, as it inhibits GC cell migration and may serve as a prognostic marker.

scholarly journals Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu Pan ◽  
Geng-yuan Hu ◽  
Shi Jiang ◽  
Shun-jie Xia ◽  
Hendi Maher ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Aerobic Glycolysis ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Sorafenib Therapy ◽  
Tumor Tissues ◽  
Cancer Genome Atlas ◽  
Advanced Stages ◽  
Disease Free

Hepatocellular carcinoma (HCC) is a deadly tumor with high heterogeneity. Aerobic glycolysis is a common indicator of tumor growth and plays a key role in tumorigenesis. Heterogeneity in distinct metabolic pathways can be used to stratify HCC into clinically relevant subgroups, but these have not yet been well-established. In this study, we constructed a model called aerobic glycolysis index (AGI) as a marker of aerobic glycolysis using genomic data of hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) project. Our results showed that this parameter inferred enhanced aerobic glycolysis activity in tumor tissues. Furthermore, high AGI is associated with poor tumor differentiation and advanced stages and could predict poor prognosis including reduced overall survival and disease-free survival. More importantly, the AGI could accurately predict tumor sensitivity to Sorafenib therapy. Therefore, the AGI may be a promising biomarker that can accurately stratify patients and improve their treatment efficacy.

scholarly journals Identification of ST7 Alteration Profile, Frequency of Alteration and Correlation with ST7-Related Genes using TCGA Data

2019 ◽  
Vol 16 (3) ◽  
pp. 217-230
Author(s):  
Nurdina CHARONG ◽  
Moltira PROMKAN
Keyword(s):  
Disease Free Survival ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Cancer Genome Atlas ◽  
Stomach Adenocarcinoma ◽  
Using Data ◽  
Liver Hepatocellular Carcinoma ◽  
Disease Free ◽  
Genome Atlas

ST7 (Suppression of Tumorigenicity 7) was reported as a protein playing a role in maintaining cellular structure. This study aims to investigate the ST7 alteration profiles and frequency of alteration in different cancers using data from The Cancer Genome Atlas (TCGA). The correlation between alterations of ST7 and angiogenesis-related genes, SERPINE1, MMP13, and VEGFA, was determined and the relation between ST7 and genes involved in suppression of ST7 transcription, PRMT5 and SMARCA4, were also analyzed. Data of 6 cancer groups from The Cancer Genome Atlas (TCGA) including ovarian serous cystadenocarcinoma (OSC), liver hepatocellular carcinoma (LHC), bladder urothelial adenocarcinoma (BUA), stomach adenocarcinoma (SC), prostate adenocarcinoma (PRAD) and glioblastoma multiforme (GBM) were downloaded for this study. The results indicated that 3 alteration patterns including amplification, missense mutation, and deletion were observed in 6 cancer studies. Gene pair between ST7 and SERPINE1 indicated the co-occurrent alteration in BUC, OSC and SC (p < 0.05). However, no association between alterations of these 2 genes and survival events in our study was observed. Shorter overall survival rate and disease-free survival were found in BUC patients with ST7, PRMT5, and  SMARCA4 alterations. These findings suggest that using TCGA data can target the potential genes involved in carcinogenesis. Combining ST7 with PRMT5 and SMARCA4 could be used as indicators for analyzing the patient survival in BUC patients and may serve as the potential therapeutic target for cancer in the future.

scholarly journals Prognostic and Immunological Role of THBS2 in Colorectal cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Bin Deng ◽  
Xiu-Ping Liu ◽  
Xiong Wang
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Bioinformatic Analysis ◽  
Histological Subtype ◽  
Free Survival ◽  
Immune Infiltration ◽  
Prognostic Analysis ◽  
Functional Mechanisms ◽  
Disease Free

Objective. Thrombospondin 2 (THBS2) acts as oncogenic or tumor suppressive gene in diverse cancers. Here we studied the prognostic and immunological role of THBS2 in colorectal cancer (CRC) using bioinformatic analysis. Methods. The genetic and protein expression of THBS2 in CRC were explored across several databases, including ONCOMINE, GEPIA2, TIMER 2.0, UALCAN and HPA databases. Correlation between THBS2 expression and clinical features in CRC was assessed using UALCAN tool. Prognostic analysis was performed using GEPIA2 and PrognoScan. Immune infiltration correlation with THBS2 in CRC was investigated with TIMER 2.0 and TISIDB. THBS2 binding and correlated genes were analyzed using String, GEPIA2, and TIMER 2.0. Results. THBS2 was significantly higher in CRC across multiple databases. Age and histological subtype were correlated with THBS2 level. High THBS2 expression correlated with short overall and disease-free survival. THBS2 expression was positively correlated with immune infiltrates in CRC. Moreover, extracellular matrix structural constituent and organization, PI3K-Akt pathway, were involved in the functional mechanisms of THBS2. Conclusions. THBS2 correlates with poor prognosis and immune infiltration in CRC. THBS2 may act as a prognostic and immunological biomarker for CRC.

scholarly journals The B7H4-PDL1 classifier stratifies immuno-phenotype in cervical cancer

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Lingyan Chen ◽  
Jianfeng Dong ◽  
Zeying Li ◽  
Yu Chen ◽  
Yan Zhang
Keyword(s):  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Sequencing Data ◽  
T Cell Infiltration ◽  
Quantitative Immunofluorescence ◽  
Ki67 Antigen ◽  
Cancer Genome Atlas ◽  
Pan Cancer

Abstract Background It has been revealed that B7H4 is negatively correlated with PDL1 and identifies immuno-cold tumors in glioma. However, the application of the B7H4-PDL1 classifier in cancers has not been well testified. Methods A pan-cancer analysis was conducted to evaluate the immunological role of B7H4 using the RNA-sequencing data downloaded from the Cancer Genome Atlas (TCGA). Immunohistochemistry (IHC) and multiplexed quantitative immunofluorescence (QIF) were performed to validate the primary results revealed by bioinformatics analysis. Results The pan-cancer analysis revealed that B7H4 was negatively correlated with PDL1 expression and immune cell infiltration in CeCa. In addition, patients with high B7H4 exhibited the shortest overall survival (OS) and relapse-free survival (RFS) while those with high PDL1 exhibited a better prognosis. Multiplexed QIF showed that B7H4 was mutually exclusive with PDL1 expression and the B7H4-high group exhibited the lowest CD8 + T cell infiltration. Besides, B7H4-high predicted highly proliferative subtypes, which expressed the highest Ki67 antigen. Moreover, B7H4-high also indicated a lower response to multiple therapies. Conclusions Totally, the B7H4-PDL1 classifier identifies the immunogenicity and predicts proliferative subtypes and limited therapeutic options in CeCa, which may be a convenient and feasible biomarker in clinical practice.

scholarly journals High miR-93 Expression Predicts Good Prognosis in Acute Myeloid Leukemia

2021 ◽  
Author(s):  
Yan Liu ◽  
Longzhen Cui ◽  
Lin Fu
Keyword(s):  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Good Prognosis ◽  
The Cancer Genome Atlas ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Prognostic Effect ◽  
Cancer Genome Atlas ◽  
Gastric Cancer Patients

Abstract Background: Overexpression of microRNA-93 (miR-93) predicted worse outcome in non-small cell lung cancer (NSCLC) and gastric cancer patients, yet the prognostic role of miR-93 in AML is still unclear.Methods: To further verify the prognostic significance of miR-93, the Cancer Genome Atlas database (TCGA) was screened and 161 AML patients with miR-93 expression information were included in our study.Results: Compared with the patients who received chemotherapy alone with lower miR-93 expression, those with higher miR-93 expression had significantly longer event-free survival (EFS) and overall survival (OS) (all P < 0.05). Moreover, the expression levels of miR-93 was no association with either EFS or OS in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Multivariate analysis confirmed that high miR-93 expression was an independent favorable factor for EFS and OS in AML patients only receiving chemotherapy (all P < 0.05).Conclusion: our study proved that high miR-93 expression could predict favorable prognosis in AML, but its prognostic effect could be overcome by allo-HSCT.

scholarly journals TP53 mutations as potential prognostic markers for specific cancers: Analysis of data from The Cancer Genome Atlas and the International Agency for Research on Cancer TP53 Database

2018 ◽  
Author(s):  
Victor Li ◽  
Karen Li ◽  
John T. Li
Keyword(s):  
Survival Time ◽  
Disease Free Survival ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
International Agency ◽  
Free Survival ◽  
Tp53 Mutations ◽  
Cancer Genome Atlas ◽  
Disease Free ◽  
Genome Atlas

AbstractMutations in the tumor suppressor gene TP53 are associated with a variety of cancers. Therefore, it is important to know the occurrence and the prognostic effects of TP53 mutations in certain cancers. Over 29,000 cases of TP53 mutations were obtained from the April 2016 release of the Internal Agency for Research on Cancer (IARC) TP53 Database, and 7,893 cancer cases were compiled in the cBioPortal for Cancer Genomics from the 33 most recent studies of The Cancer Genome Atlas (TCGA). The data was analyzed, and it was found that the majority of TP53 mutations were missense and the major mutational hotspots were located at codons 248, 273, 175, and 245 in exons 4–8 for somatic mutations with the addition of codon 337 and other mutations in exons 9–10 for germline mutations. Out of 33 TGCA studies, the effects of TP53 mutations were statistically significant in ten cancers (ovarian serous cystadenocarcinoma, lung adenocarcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, acute myeloid leukemia, clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, uterine endometrial carcinoma, and thymoma) for survival time and in six cancers (ovarian serous cystadenocarcinoma, pancreatic adenocarcinoma, hepatocellular carcinoma, chromophobe RCC, acute myeloid leukemia, and thymoma) for disease-free survival time. Also, it was found that the most common p53 mutation in hepatocellular carcinomas (R249S) was a much better indicator for poor prognosis than TP53 mutations as a whole.Author summaryThe TP53 gene codes for the tumor suppressor protein, p53, which is essential for DNA repair, cell cycle arrest, and apoptosis. It is commonly inactivated or partially disabled by mutations, contributing to the development of a variety of human cancers. In this study, over 29,000 cases from the April 2016 release of the International Agency for Research on Cancer TP53 Database (IARC) were analyzed to determine the distribution of mutations in the TP53 gene. Data was also collected from the 33 most recent The Cancer Genome Atlas (TCGA) studies to determine the prevalence of TP53 mutations in cancers and their effects on survival and disease-free survival time. It was found that there were statistically significant differences between cases with and without TP53 mutations in ten cancers when comparing survival time, and in six cancers when comparing disease-free survival time. This indicates that TP53 mutations are potential prognostic markers that can be used to further improve the accuracy of predicting the survival time and disease-free survival time of cancer patients.

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