scholarly journals FAM65A as a novel prognostic biomarker in human tumors reveal by a pan-cancer analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenken Liang ◽  
Chune Mo ◽  
Jianfen Wei ◽  
Wei Chen ◽  
Weiwei Gong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Biomarker ◽  
Malignant Tumors ◽  
Sequence Similarity ◽  
Human Tumor ◽  
Colon Adenocarcinoma ◽  
Human Tumors ◽  
The Cancer Genome Atlas ◽  
Different Types ◽  
Pan Cancer

Abstract Background Family with sequence similarity 65 member A (FAM65A), also known as RIPOR1, is differentially expressed between human tumor and non-tumor tissues in kinds of cancers. In addition, it was reported that the product of FAM65A may be a biomarker for cholangiocarcinoma patients. However, there is still no evidence on the relationship between the FAM65A and different types of tumors. Our study is mainly for exploring the prognostic values of FAM65A in pan-cancer and for further discovering a potential therapeutics target. Methods We analyzed FAM65A expression, prognostic values, genetic alteration, protein phosphorylation, immune infiltration and enrichment analysis across different types of human malignant tumors based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Additionally, Real-Time PCR (RT-qPCR) was performed to further confirm the roles of FAM65A in the pathogenesis of colorectal cancer. Results We found that FAM65A expression was associated with the prognosis of multiple human tumors, especially colorectal cancer. Moreover, we also observed that FAM65A was highly expressed in colorectal cancer through RT-qPCR. We observed that decreasing phosphorylation level of the S351 locus in colon adenocarcinoma, uterine corpus endometrial carcinoma and lung adenocarcinoma. And the expression of FAM65A was positively related to cancer-associated fibroblasts (CAFs) infiltration in many tumors, such as colon adenocarcinoma. Therefore, FAM65A may be a potential prognostic biomarker of human tumors.

scholarly journals Prognostic Value and Immune Characteristics of RUNX Family in Human Cancers: A Pan-cancer Analysis

2021 ◽  
Author(s):  
Han Zhao ◽  
Yun Chen ◽  
Peijun Shen ◽  
Lan Gong
Keyword(s):  
Gene Expression ◽  
Gene Family ◽  
Immune Cell ◽  
Malignant Tumors ◽  
Genetic Alterations ◽  
Genetic Mutation ◽  
The Cancer Genome Atlas ◽  
Different Types ◽  
Cancer Types ◽  
Pan Cancer

Abstract Background: Runt‑related transcription factors (RUNX) are involved in numerous fundamental biological processes and play crucial parts in tumorigenesis and metastasis both directly and indirectly. However, the pan-cancer evidence of RUNX gene family is no available. Methods: In this study, we analyzed the potential association between RUNX gene family expression and patient’s prognosis, immune cell infiltration, drug response, and genetic mutation data across different types of tumors using based on The Cancer Genome Atlas, Gene Expression Omnibus, and Oncomine database. Results: The results showed that the expression of the RUNX family varied among different cancer types, revealing its heterogeneity in cancers, and that expression of RUNX2 was lower than that of RUNX1 and RUNX3 across all cancer types. RUNX family gene expression was related to prognosis in several cancers. Furthermore, our study revealed a clear association between RUNX family expression and ESTIMATE score, RNA stemness, and DNA stemness scores. Compared with RUNX1 and RUNX2, RUNX3 showed relatively low levels of genetic alterations. RUNX family genes had clear associations with immune infiltrate subtypes, and their expression was positively related to immune checkpoint genes and drug sensitivity in most cases. Conclusions: These findings will help to elucidate the potential oncogenic roles of RUNX family genes in different types of cancer and it can function as a prognostic marker in various malignant tumors.

scholarly journals Modularity of the metabolic gene network as a prognostic biomarker for hepatocellular carcinoma

2017 ◽  
Author(s):  
Fengdan Ye ◽  
Dongya Jia ◽  
Mingyang Lu ◽  
Herbert Levine ◽  
Michael W Deem
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Biomarker ◽  
Malignant Tumors ◽  
Aerobic Glycolysis ◽  
Expression Patterns ◽  
Cancer Recurrence ◽  
Metabolic Reprogramming ◽  
The Cancer Genome Atlas ◽  
Driver Genes ◽  
Tumor Stages

AbstractAbnormal metabolism is an emerging hallmark of cancer. Cancer cells utilize both aerobic glycolysis and oxidative phosphorylation (OXPHOS) for energy production and biomass synthesis. Understanding the metabolic reprogramming in cancer can help design therapies to target metabolism and thereby to improve prognosis. We have previously argued that more malignant tumors are usually characterized by a more modular expression pattern of cancer-associated genes. In this work, we analyzed the expression patterns of metabolism genes in terms of modularity for 371 hepatocellular carcinoma (HCC) samples from the Cancer Genome Atlas (TCGA). We found that higher modularity significantly correlated with glycolytic phenotype, later tumor stages, higher metastatic potential, and cancer recurrence, all of which contributed to poorer prognosis. Among patients with recurred tumor, we found the correlation of higher modularity with worse prognosis during early to mid-progression. Furthermore, we developed metrics to calculate individual modularity, which was shown to be predictive of cancer recurrence and patients’ survival and therefore may serve as a prognostic biomarker. Our overall conclusion is that more aggressive HCC tumors, as judged by decreased host survival probability, had more modular expression patterns of metabolic genes. These results may be used to identify cancer driver genes and for drug design.

TRPV4 is a Prognostic Biomarker That Correlates With the Immunosuppressive Microenvironment and Chemoresistance of Anti-Cancer Drugs

2021 ◽  
Author(s):  
kai wang ◽  
Jun xing Feng ◽  
Zhi ling Zheng ◽  
Ying ze Chai ◽  
Hui jun Yu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Transient Receptor Potential ◽  
Immune Cell ◽  
Colon Adenocarcinoma ◽  
Enrichment Analysis ◽  
Receptor Potential ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Free Interval ◽  
Pan Cancer

Abstract Background: Transient receptor potential cation channel subfamily V member 4 (TRPV4) has been reported to regulate tumor progression in many tumor types. However, its association with the tumor immune microenvironment remains unclear.Methods: TRPV4 expression was assessed using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. The clinical features and prognostic roles of TRPV4 were assessed using TCGA cohort. Gene set enrichment analysis (GSEA) of TRPV4 was conducted using the R package clusterProfiler. We analyzed the association between TRPV4 and immune cell infiltration scores of TCGA samples downloaded from published articles and the TIMER2 database.Results: TRPV4 was highly expressed and associated with worse overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) in colon adenocarcinoma (COAD) and ovarian cancer. Furthermore, TRPV4 expression was closely associated with immune regulation-related pathways. Moreover, tumor-associated macrophage (TAM) infiltration levels were positively correlated with TRPV4 expression in TCGA pan-cancer samples. Immunosuppressive genes such as PD-L1, PD-1, CTLA4, LAG3, TIGIT, TGFB1, and TGFBR1 were positively correlated with TRPV4 expression in most tumors.Conclusions: Our results suggest that TRPV4 is an oncogene and a prognostic marker in COAD and ovarian cancer. High TRPV4 expression is associated with tumor immunosuppressive status and may contribute to TAM infiltration based on TCGA data from pan-cancer samples.

scholarly journals The Role of lncRNA PCAT6 in Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Siying Wang ◽  
Zhenyao Chen ◽  
Jingyao Gu ◽  
Xin Chen ◽  
Zhaoxia Wang
Keyword(s):  
Breast Cancer ◽  
Prognostic Biomarker ◽  
Malignant Tumors ◽  
Vital Role ◽  
Cancer Breast ◽  
Non Coding Rna ◽  
Different Types ◽  
Cancer Côlon ◽  
Long Non Coding Rna

Long non-coding RNA (lncRNA) PCAT6 is a member of the Prostate Cancer Associated Transcripts family of molecules. In this review, we focus on the latest studies involving PCAT6 in the diagnosis, treatment, and prognosis of malignant tumors of the digestive, respiratory, urinary, reproductive, motion, and nervous systems. PCAT6 was found to be highly expressed in gastric cancer, colon cancer, hepatocellular carcinoma, lung cancer, bladder cancer, ovarian cancer, breast cancer, cervical cancer, osteosarcoma, glioblastoma, and other tumors. PCAT6 can promote the development and progression of different types of malignant tumors through various mechanisms. Overall, these findings suggest that PCAT6 may play an increasingly vital role in the clinical assessment of these malignant tumors. It can function as an oncogene and may be used as a potential new prognostic biomarker of these tumors.

scholarly journals Potential Biomarkers of Colon Adenocarcinoma Based on Weighted Gene Co-Expression Network Analysis

2021 ◽  
Author(s):  
Zhongze Cui ◽  
Shuang He ◽  
Feifei Wen ◽  
Xiaoyang Xu ◽  
Yangyang Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Colon Cancer ◽  
Network Analysis ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Colon Adenocarcinoma ◽  
The Cancer Genome Atlas ◽  
Future Research ◽  
Related Gene

Abstract Background: Colon adenocarcinoma (COAD) is one of the most common malignancies worldwide. Although a large number of studies have elucidated the aetiology of colorectal cancer, the exact mechanism of colorectal cancer development remains to be determined.To identify key modules and prognostic genes that may be involved in the occurrence and development of COAD, weighted gene coexpression network analysis (WGCNA) and differential expression analysis were performed on datasets GSE41657 and GSE74602 from the Gene Expression Omnibus (GEO) database to screen for prognostic differentially expressed genes. Gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database for verification.Results: Through WGCNA and DEGs analysis, 439 genes in key functional modules were obtained, and 26 prognostic related genes were finally obtained through prognostic analysis: (1) We screened 5 genes（RPP40, DUSP18, PPRC1, MFSD11 and PDCD11） that have not been studied in COAD.（2）We obtained the most critical module in the occurrence and development of colon cancer and obtained one prognosis-related gene, NUP85, from the most critical module.The relationship between it and tumor immune microenvironment was verified.（3） A prognostic model comprising four coexpressed differential genes was constructed; TIMP1, PMM2, E2F3 and MORC2 were selected as the key prognosis-related genes.Conclusions: （1）As new biomarkers，prognostic genes RPP40, DUSP18, PPRC1, MFSD11 and PDCD11 may be potential therapeutic targets for COAD, and provide new ideas for future research on the mechanism of COAD. （2）NUP85 may be an immune-related gene which was negatively correlated with CD4+ T cell and M2 macrophagesthat plays an important role in inhibiting the occurrence and development of colorectal adenocarcinoma. （3）A Cox proportional risk model based on gene expression can be used to predict the prognosis and survival time of patients with colon cancer.

scholarly journals A Pan-cancer Analysis of Thioredoxin-interacting Protein as an Immunological and Prognostic Biomarker

2022 ◽  
Author(s):  
Xuxue Guo ◽  
Mei Huang ◽  
Haonan Zhang ◽  
Qianhui Chen ◽  
Ying Hu ◽  
...  
Keyword(s):  
Immune Cell ◽  
Prognostic Biomarker ◽  
Redox Homeostasis ◽  
Critical Role ◽  
The Cancer Genome Atlas ◽  
Inflammasome Activation ◽  
Post Translational Modification ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Pan Cancer

Abstract BackgroundThe critical role of thioredoxin-interacting protein (TXNIP) in cellular sulfhydryl redox homeostasis and inflammasome activation is already widely known, however, no pan-cancer analysis is currently available. MethodsWe thus first explored the potential roles of TXNIP across thirty-three tumors mainly based on The Cancer Genome Atlas and Gene Expression Omnibus datasets. ResultsTXNIP is lowly expressed in most cancers, and distinct associations exist between TXNIP expression and the prognosis of tumor patients. TXNIP expression was associated with tumor mutational burden, microsatellite instability, mismatch repair genes, tumor infiltrating immune cell abundance as well as cancer-associated fibroblasts. Moreover, ubiquitin mediated proteolysis, protein post-translational modification and other related pathways were involved in the functional mechanisms of TXNIP. ConclusionsOur first pan-cancer study offers a relatively comprehensive understanding of the carcinostatic roles of TXNIP across different tumors. And this molecule may be considered as a potential immunological and prognostic biomarker.

scholarly journals INHBB Is a Novel Prognostic Biomarker Associated with Cancer-Promoting Pathways in Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Jinpeng Yuan ◽  
Aosi Xie ◽  
Qiangjian Cao ◽  
Xinxin Li ◽  
Juntian Chen
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Disease Free Survival ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction

Background. Inhibin subunit beta B (INHBB) is a protein-coding gene that participated in the synthesis of the transforming growth factor-β (TGF-β) family members. The study is aimed at exploring the clinical significance of INHBB in patients with colorectal cancer (CRC) by bioinformatics analysis. Methods. Real-time PCR and analyses of Oncomine, Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases were utilized to evaluate the INHBB gene transcription level of colorectal cancer (CRC) tissue. We evaluated the INHBB methylation level and the relationship between expression and methylation levels of CpG islands in CRC tissue. The corresponding clinical data were obtained to further explore the association of INHBB with clinical and survival features. In addition, Gene Set Enrichment Analysis (GSEA) was performed to explore the gene ontology and signaling pathways of INHBB involved. Results. INHBB expression was elevated in CRC tissue. Although the promoter of INHBB was hypermethylated in CRC, methylation did not ultimately correlate with the expression of INHBB. Overexpression of INHBB was significantly and positively associated with invasion depth, distant metastasis, and TNM stage. Cox regression analyses and Kaplan-Meier survival analysis indicated that high expression of INHBB was correlated with worse overall survival (OS) and disease-free survival (DFS). GSEA showed that INHBB was closely correlated with 5 cancer-promoting signaling pathways including the Hedgehog signaling pathway, ECM receptor interaction, TGF-β signaling pathway, focal adhesion, and pathway in cancer. INHBB expression significantly promoted macrophage infiltration and inhibited memory T cell, mast cell, and dendritic cell infiltration. INHBB expression was positively correlated with stromal and immune scores of CRC samples. Conclusion. INHBB might be a potential prognostic biomarker and a novel therapeutic target for CRC.

scholarly journals MicroRNA-Related Prognosis Biomarkers from High-Throughput Sequencing Data of Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xiao-Liang Xing ◽  
Zhi-Yong Yao ◽  
Ti Zhang ◽  
Ning Zhu ◽  
Yuan-Wu Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Differential Expression ◽  
High Throughput Sequencing ◽  
Survival Rates ◽  
Colon Adenocarcinoma ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
High Throughput Sequencing Data ◽  
Differential Expression Genes ◽  
Cancer Genome Atlas

Background. Colorectal cancer (CRC) is the third most common cancer in the world, and most of them are adenocarcinomas. CRC could be classified as colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) according to the original tumorigenesis position. Increasing evidences indicated that microRNAs (miRNAs) play an important role in the occurrence of multiple tumors. Methods. In this study, we firstly downloaded miRNA (COAD, 8 controls vs. 455 tumors; READ, 3 controls vs. 161 tumors) and mRNA (COAD, 41 controls vs. 478 tumors; READ, 10 controls vs. 166 tumors) data from The Cancer Genome Atlas (TCGA) database and then used DESeq2, RegParallel, miRDB, TargetScanHuman 7.2, DAVID 6.8, STRING, and Cytoscape software to identify the potential prognosis biomarkers. Results. We identified 175 differential expression miRNAs (DEMs) and 3747 differential expression genes (DEGs) in COAD and 184 DEMs and 3928 DEGs in READ. And then, we obtained 21 (13 in COAD and 8 in READ) DEMs associated with the survival rates, which correlated with 440 (217 in COAD and 223 in READ) overlapping DEGs. Through survival analysis for those overlapping DEGs, we found 11 (8 in COAD and 3 in READ) overlapping DGEs associated with survival rates of patients, which were correlated with 9 (7 in COAD and 2 in READ) DEMs significantly. Conclusion. In this study, we found several candidate prognostic biomarkers which have been identified in various cancers and also found several new prognosis biomarkers of COAD and READ. In conclusion, this analysis based on theoretical knowledge and clinical outcomes we have done needs further confirmation by more researches.

The predictive values of loss-of-function variants in histone methyltransferases for response to immune checkpoint inhibitors in solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2586-2586
Author(s):  
Naixin Liang ◽  
Yanling Niu ◽  
Xin Zhang ◽  
Tonghui Ma
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Cancer Colorectal ◽  
Checkpoint Inhibitors ◽  
Loss Of Function ◽  
Cancer Dataset ◽  
Predictive Values ◽  
Histone Methyltransferases ◽  
Different Types ◽  
Pan Cancer

2586 Background: Dysregulation of histone methyltransferases (HMTs) has been reported to play critical roles in cancer development. Previous studies showed that many HMTs were recruited to DNA damage sites where they posttranslationally modified chromatin to regulate chromatin-based DNA damage repair (DDR) activities. We hypothesized that loss-of-function (LOF) variants of HMTs may associate with genome instability and tumor mutational burden (TMB). Thus, we explored the associations of LOF variants in some HMTs with TMB and benefit from immune checkpoint inhibitors (ICIs) in solid tumors. Methods: An ICIs treatment cohort from the Memorial Sloan Kettering Cancer Center (MSKCC) was analyzed. The following solid tumor types were enrolled: NSCLC (n = 350), colorectal cancer (n = 110), bladder cancer (n = 215), breast cancer (n = 44), esophagogastric cancer (n = 126), head and neck cancer (n = 139), glioma (n = 117), melanoma (n = 320), and renal cell carcinoma (n = 151). We evaluated 15 HMTs (KMT2A, KMT2B, KMT2C, KMT2D, SETD2, SETD8, EZH1, EZH2, PRDM1, PRDM14, SMYD3, NSD1, WHSC1, WHSC1L1, and DOT1L). Results: The data revealed that LOF variants of KMT2D, SETD2, and KMT2C were more frequent in pan-cancer dataset. Furthermore, we found that LOF variants of 7 HMTs, including KMT2A, KMT2B, KMT2C, KMT2D, NSD1, SETD2, and EZH2, were associated with higher TMB (P < 0.0001). Then we analyzed the associations between LOF variants and overall survival (OS) after ICIs therapy. The results indicated that LOF variants of KMT2A (P = 0.0295), KMT2B (P = 0.0329), KMT2C (P = 0.0122), and SETD2 (P = 0.0004) were significantly associated with prolonged median OS for all the enrolled patients. In this cohort, LOF variants of KMT2A, KMT2B, KMT2C, and SETD2 were most common in bladder cancer, colorectal cancer, colorectal cancer, and renal cell carcinoma, respectively. Then we assessed the predictive values of these four genes for each type of cancer. It was noteworthy that KMT2C LOF variants were significantly correlated with longer median OS in colorectal cancer (P = 0.0171), but not in other cancer types. Surprisingly, we did not observe the predictive roles of LOF variants in KMT2A, KMT2B, and SETD2 genes for response to ICIs therapy in any types of cancer. Conclusions: In pan-cancer dataset, we found that LOF variants of 4 HMTs, such as KMT2A, KMT2B, KMT2C, and SETD2, were correlated with better outcomes of ICIs treatment. However, for different types of cancer, only KMT2C LOF variants were associated with longer median OS in colorectal cancer, suggesting that it may be used as a predictive biomarker for ICIs efficacy in colorectal cancer. Because the sample sizes of patients with KMT2A, KMT2B, or SETD2 LOF variants were small, we did not find the predictive values of LOF variants in these three genes for different types of cancer. Next, we will enroll more patients to address this question.

scholarly journals Hyperprogressive Disease Caused by PD-1 Inhibitors for the Treatment of Pan-Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Shiyun Chen ◽  
Miaomiao Gou ◽  
Huan Yan ◽  
Mengjiao Fan ◽  
Yuting Pan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Tumor Markers ◽  
Malignant Tumors ◽  
Hepatic Metastases ◽  
Lactate Dehydrogenase Level ◽  
Tumor Growth Rate ◽  
Hyperprogressive Disease ◽  
Metastatic Sites ◽  
Pan Cancer

Background. Nowadays, PD-1/PD-L1 inhibitors are widely used to treat various malignant tumors. However, during the immunotherapy in a few patients, a flare-up of tumor growth occurred. This new pattern of progression is called hyperprogressive disease (HPD). Patients and Methods. The retrospective study included 377 patients with various malignant tumors treated with PD-1 inhibitors (nivolumab or pembrolizumab) in the Chinese PLA General Hospital from January 2015 to January 2019. Clinicopathologic variables, tumor growth rate (TGR), and treatment outcomes were analyzed in patients with pan-cancer treated with PD-1 inhibitors. HPD was defined as the difference of TGR before and during immunotherapy exceeding 50%. Results. In 38 of 377 patients (10.08%), HPD occurred after treatment with PD-1 inhibitors. Patients with HPD had lower overall survival (OS) than those without HPD (median OS, 3.6months (95% CI, 3.0–4.2) vs. 7.3 months (95% CI, 5.9–8.7); P < 0.01 ). Factors related to HPD include more than 2 metastatic sites, ECOG performance status ≥ 2 , hepatic metastases, and lactate dehydrogenase level greater than normal upper limit. KRAS status was significantly associated with HPD in patients with colorectal cancer. In the exploratory predictors’ analysis, the rapid increase of characteristic tumor markers (such as CEA in colorectal cancer, CA199 in pancreatic cancer and cholangiocarcinoma) within one month was found to be associated with the occurrence of HPD. Conclusions. HPD was developed with different rates in a variety of malignant tumor patients treated with PD-1 inhibitors and related to some clinicopathological features and poor prognosis. Tumor markers, especially CA199, might be served as early predictors of HPD.

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