scholarly journals A Multilevel Systemic Pan-cancer Analysis: Collagen Triple Helix Repeat Containing-1 is a Potential Target for Tumor Immunotherapy

2021 ◽  
Author(s):  
Jiangtao Zhang ◽  
Xianghua Wu ◽  
Huichao Ruan ◽  
Changli Wang ◽  
Rong qiang Yang ◽  
...  
Keyword(s):  
Immune Cell ◽  
Tumor Immunotherapy ◽  
Genomic Changes ◽  
Collagen Triple Helix ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
Bioinformatics Databases ◽  
Cell Components ◽  
Cancer Tissues ◽  
Pan Cancer

Abstract Background: Cancer is one of the leading causes of pathological death in humans. Although CTHRC1 is a prooncogene highly expressed in a variety of tumor tissues, the specific biological mechanisms of CTHRC1 involvement in cancer development need to be elucidated. Methods: In the present study, nine online bioinformatics databases were employed to explore the potential prognostic and grading value of CTHRC1 in generalized cancer as well as its potential role in regulating tumor immunity. Results: Data from GEPIA2.0, Oncomine, TNMplot, Kaplan-Meier Plotter and TISIDB database had consistently demonstrated that CTHRC1 was associated with the expression, prognosis and typing in most cancer tissues. Cbioportal and SMART analysis revealed that genomic changes and methylation of CTHRC1 in most tumor tissues. Finally, Sangerbox and TIMER database analysis suggested that CTHRC1 was involved in the changes of immune cell components in tumor immune microenvironment, with certain heterogeneity. Meanwhile, CTHRC1 was correlated with TMB, MSI, neoantigen and tumor immune checkpoint, especially CD276. Conclusion: CTHRC1 had the potential as a prognostic and grading molecular marker for pan-cancer. And CTHRC1-related targeting agents may be a novel breakthrough in tumor immunotherapy.

scholarly journals SLC2A5 Correlated with Immune Infiltration: A Candidate Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Lianxiang Luo ◽  
Jiating Su ◽  
Yushi Zheng ◽  
Fangfang Huang ◽  
Riming Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Clinical Feature ◽  
Lung Cancer Patients ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
Kaplan Meier Plotter

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer with a relatively poor prognosis, requiring novel therapeutic approaches. Great advances in new immunotherapy strategies have shown encouraging results in lung cancer patients. This study is aimed at elucidating the function of SLC2A5 in the prognosis and pathogenesis of LUAD by analyzing public databases. The differential expression of SLC2A5 in various tissues from Oncomine, GEPIA, and other databases was obtained, and SLC2A5 expression at the protein level in normal and tumor tissues was detected with the use of the HPA database. Then, we used the UALCAN database to analyze the expression of SLC2A5 in different clinical feature subgroups. Notably, in both PrognoScan and Kaplan-Meier plotter databases, we found a certain association between SLC2A5 and poor OS outcomes in LUAD patients. Studies based on the TIMER database show a strong correlation between SLC2A5 expression and various immune cell infiltrates and markers. The data analysis in the UALCAN database showed that the decreased promoter methylation level of SLC2A5 in LUAD may lead to the high expression of SLC2A5. Finally, we used the LinkedOmics database to evaluate the SLC2A5-related coexpression and functional networks in LUAD and to investigate their role in tumor immunity. These findings suggest that SLC2A5 correlated with immune infiltration can be used as a candidate diagnostic and prognostic biomarker in LUAD patients.

scholarly journals Systematic Analysis of the Oncogenic Role of WDR62 in Human Tumors

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Yulan Bu ◽  
Lihua Zhang ◽  
Xiaolin Ma ◽  
Rui Wang ◽  
Xuecheng Zhang ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Immune Cell ◽  
Treg Cells ◽  
Human Tumors ◽  
Systematic Analysis ◽  
Kaplan Meier ◽  
Promoter Dna ◽  
Underlying Mechanisms ◽  
Pan Cancer

Background. Emerging studies support the oncogenic role of WD repeat domain 62 (WDR62) in few tumors, while no pan-cancer analysis is available. In this study, we analyzed systematically the oncogenic role of WDR62 across a series of human tumors based on bioinformatic data mining. Methods. The expression level of WDR62 was analyzed via GEPIA2, TIMER, UALCAN, and StarBase databases. The prognostic role was analyzed via GEPIA2, TIMER, UALCAN, StarBase, TISIDB, TCGA portal, Kaplan-Meier Plotter, and PrognoScan databases. Then, we explored the causes for WDR62 abnormal expression via TCGA portal and UALCAN databases. Subsequently, the STRING and GeneMANIA databases were used to find the interactive networks for WDR62. Furthermore, we analyzed the correlation between WDR62 expression and immune features via TIMER and TISIDB databases. Results. We found that WDR62 was significantly upregulated in most of the tumors and correlated with poor prognosis mainly in 6 candidate tumors—BLCA, BRCA, KIRC, KIRP, LIHC, and LUAD. Abnormal WDR62 expression may be probably attributed to TP53 mutation and promoter DNA methylation. Relative network analysis demonstrated that WDR62 was mainly involved in MAPK and toll-like receptor signaling pathway. WDR62 expression was associated with various immune cell infiltrations, especially cancer-associated fibroblasts (CAF) and T cell regulatory (Treg) cells, and was markedly correlated with poor prognosis. Moreover, WDR62 expression was closely associated with the expression of some immunomodulators such as PD-L1 and has a significant prognostic value. Conclusions. Our study revealed that WDR62 could serve as a diagnostic and prognostic biomarker for several cancers. Importantly, WDR62 was closely associated with various immune cell infiltration, and to a certain extent, it can predict the effect of immunotherapy in particular PD1/PD-L1 inhibitors. Our pan-cancer study provided useful information on the oncogenic role of WDR62, contributing to further exploring the underlying mechanisms.

scholarly journals Non-immune Cell Components in the Gastrointestinal Tumor Microenvironment Influencing Tumor Immunotherapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhengshuo Li ◽  
Xiaoyue Zhang ◽  
Can Liu ◽  
Jian Ma
Keyword(s):  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Immune Cell ◽  
Tumor Immunotherapy ◽  
Gastrointestinal Tumor ◽  
Key Factors ◽  
Immune Microenvironment ◽  
Soluble Factors ◽  
Susceptibility Factors ◽  
Cell Components

Interactions of genetic susceptibility factors, immune microenvironment, and microbial factors contribute to gastrointestinal tumorigenesis. The suppressive immune microenvironment reshaped by the tumors during gastrointestinal tumorigenesis directly contributes to T-cell depletion in tumor immunotherapy. Soluble factors secreted by tumor cells or stromal cells collectively shape the suppressive immune environment. Here, we reviewed the key factors in the gastrointestinal tumor microenvironment that influence tumor immunotherapy, focusing on the effects of fibroblasts, neuronal cells, soluble cytokines, exosomes, and the microbiome in tumor microenvironment. Research in this field has helped to identify more precise and effective biomarkers and therapeutic targets in the era of tumor immunotherapy.

scholarly journals Identification of a five-gene prognostic signature related to B cells infiltration in pancreatic adenocarcinoma

2021 ◽  
Author(s):  
Shaomei Tang ◽  
Xiaoliang Huang ◽  
Haixing Jiang ◽  
Shanyu Qin
Keyword(s):  
B Cells ◽  
Pancreatic Adenocarcinoma ◽  
Immune Cells ◽  
Immune Cell ◽  
Cox Regression ◽  
Risk Scores ◽  
Prognostic Signature ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Cell Components

Abstract Background: Pancreatic adenocarcinoma (PAAD) is an extremely malignant cancer. Immunotherapy is a promising avenue for elevating survival time of PAAD patients.Methods: The RNA sequencing and clinical data of PAAD were downloaded from the TCGA database. The ssGSEA method and weighted gene co-expression network analysis were used to calculate the relative abundance of tumor-infiltrated immune cells and identified the immune cells closely related module. Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis were used to construct a prognostic model. MCPcounter and EPIC were also applied to assess the immune cell components using gene expression profile.Results: The B cells closely related module was identified and five genes including ARID5A, CLEC2B, MICAL1, MZB1 and RAPGEF1 were ultimately selected to establish the prognostic signature for calculating risk scores of PAAD patients. Kaplan-Meier curves presented a worse survival in the high-risk patients (p<0.05) and the area under the Receiver operating characteristic (ROC) curve of risk score for 1-year and 3-year survival were 0.78 and 0.80 based on the training set. Also, similar results were verified in the validated and combined sets. Interestingly, low-risk group presented significantly elevated immune, stroma scores and proportion of B cells and associations between these five genes and B cells were identified by using multiple methods including ssGSEA, MCPcounter and EPIC. Conclusions: This is the first attempt to study a B cells related prognostic signature, which is instrumental in exploration of novel prognostic biomarkers in PAAD.

scholarly journals Prognostic and Immunological Role of Key Genes of Ferroptosis in Pan-Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhi-Zhou Shi ◽  
Hao Tao ◽  
Ze-Wen Fan ◽  
Sheng-Jie Song ◽  
Jie Bai
Keyword(s):  
Expression Patterns ◽  
Disease Free Survival ◽  
M2 Macrophage ◽  
Expression Levels ◽  
Interactive Analysis ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
Apoptosis Inducing Factor ◽  
Pan Cancer

Solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), and apoptosis inducing factor mitochondria associated 2 (AIFM2) are the key regulators in ferroptosis. However, the expression patterns and prognostic roles of these genes in pan-cancer are still largely unclear. The expression patterns and prognostic roles of SLC7A11, GPX4, and AIFM2 and the relationships between the expression levels of these genes and immune infiltration levels in pan-cancer were analyzed by using TIMER, gene expression profiling interactive analysis (GEPIA), Oncomine, and Kaplan–Meier databases. Our results showed that both SLC7A11 and GPX4 were overexpressed in colorectal cancer, and SLC7A11 was overexpressed in lung cancer. High levels of SLC7A11 and AIFM2 were significantly linked with the shortened disease-free survival and overall survival (OS) in adrenocortical carcinoma (ACC), respectively. And high expression of SLC7A11, GPX4, and AIFM2 were significantly correlated with the shortened OS of acute myeloid leukemia patients. In esophageal carcinoma (ESCA), GPX4 expression was significantly associated with the infiltration of macrophage and myeloid dendritic cell, and AIFM2 expression was significantly associated with the infiltration of CD4+ T cell. Importantly, GPX4 expression was positively correlated with the expression levels of monocyte markers (CD14 and CD115) and M2 macrophage markers (VSIG4 and MS4A4A) both in ESCA and in head and neck squamous cell carcinoma (HNSC). In summary, SLC7A11, GPX4, and AIFM2 are dysregulated in many types of cancers, and are candidate prognostic biomarkers for many types of cancers, and can be used to evaluate the infiltration of immune cells in tumor tissues.

scholarly journals High Apelin Level Indicates a Poor Prognostic Factor in Muscle-Invasive Bladder Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Long Yang ◽  
Yan-Lei Li ◽  
Xiao-Qing Li ◽  
Zheng Zhang
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Vascular Invasion ◽  
Tumor Stage ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
High Tumor Stage ◽  
Muscle Invasive

Purpose. To compare the expression level of apelin in muscle-invasive bladder cancer and matched paracarcinoma tissues and investigate the relationship between apelin and clinical prognosis in the patients. Methods. To assess apelin expression by using immunohistochemical method compared with bladder tumors and matched paracarcinoma tissues. Subsequently, the correlation of apelin expression with the clinicopathological features of bladder cancer patients was analyzed. Kaplan-Meier survival curves method was used to analyze apelin prognostic significance for muscle-invasive bladder cancer patients (including 404 muscle-invasive bladder cancer patients and 28 normal bladder tissues, in TCGA dataset). Results. Apelin protein level was overexpressed in bladder tumor tissues compared with paracarcinoma tissues. Furthermore, high apelin expression was associated with high tumor stage (P<0.05), distant metastasis (P<0.05), and vascular invasion (P<0.05). Kaplan-Meier curve analyses showed that the overexpression of apelin was a potential predictor of overall survival and disease-free survival. Conclusion. Apelin was upregulated in bladder tumor tissues compared with matched adjacent noncancer tissues, especially in the high tumor stage, distant metastasis, and vascular invasion. What is more, high expression of apelin in muscle-invasive bladder cancer indicates the poor prognosis. These data suggested that apelin might be a therapeutic potential biomarker in muscle-invasive bladder cancer patients.

scholarly journals Pan-cancer characterization of lncRNA modifiers of immune microenvironment reveals clinically distinct de novo tumor subtypes

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zicheng Zhang ◽  
Congcong Yan ◽  
Ke Li ◽  
Siqi Bao ◽  
Lei Li ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Immune Cell ◽  
De Novo ◽  
Solid Cancer ◽  
Immune Microenvironment ◽  
Cancer Subtypes ◽  
Tumor Subtypes ◽  
Cancer Immunity ◽  
Systems Immunology ◽  
Pan Cancer

AbstractThe emerging field of long noncoding RNA (lncRNA)-immunity has provided a new perspective on cancer immunity and immunotherapies. The lncRNA modifiers of infiltrating immune cells in the tumor immune microenvironment (TIME) and their impact on tumor behavior and disease prognosis remain largely uncharacterized. In the present study, a systems immunology framework integrating the noncoding transcriptome and immunogenomics profiles of 9549 tumor samples across 30 solid cancer types was used, and 36 lncRNAs were identified as modifier candidates underlying immune cell infiltration in the TIME at the pan-cancer level. These TIME lncRNA modifiers (TIL-lncRNAs) were able to subclassify various tumors into three de novo pan-cancer subtypes characterized by distinct immunological features, biological behaviors, and disease prognoses. Finally, a TIL-lncRNA-derived immune state index (TISI) that was reflective of immunological and oncogenic states but also predictive of patients’ prognosis was proposed. Furthermore, the TISI provided additional prognostic value for existing tumor immunological and molecular subtypes. By applying the TISI to tumors from different clinical immunotherapy cohorts, the TISI was found to be significantly negatively correlated with immune-checkpoint genes and to have the ability to predict the effectiveness of immunotherapy. In conclusion, the present study provided comprehensive resources and insights for future functional and mechanistic studies on lncRNA-mediated cancer immunity and highlighted the potential of the clinical application of lncRNA-based immunotherapeutic strategies in precision immunotherapy.

scholarly journals RNA-sequencing identified miR-3681 as a negative regulator in the proliferation and migration of cervical cancer cells via the posttranscriptional suppression of HGFR

RSC Advances ◽  
2019 ◽  
Vol 9 (39) ◽  
pp. 22376-22383 ◽  
Author(s):  
Fan Shi ◽  
Yingbing Zhang ◽  
Juan Wang ◽  
Jin Su ◽  
Zi Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Rna Sequencing ◽  
Negative Regulator ◽  
Tumor Tissues ◽  
Differentially Expressed Mirnas ◽  
Cervical Cancer Cells ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

In this study, RNA-sequencing was used to investigate the differentially expressed miRNAs between cervical cancer tissues and matched adjacent non-tumor tissues.

scholarly journals TSP-1-1223 A/G Polymorphism as a Potential Predictor of the Recurrence Risk of Bladder Cancer in a Chinese Population

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Xiao Yang ◽  
Pengchao Li ◽  
Xuejian Yang ◽  
Chao Qin ◽  
Qiang Cao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Chinese Population ◽  
Recurrence Risk ◽  
Taqman Assay ◽  
Control Subjects ◽  
Kaplan Meier ◽  
Genotype Frequencies ◽  
Healthy Control ◽  
First Recurrence ◽  
Cancer Tissues

Backgrounds. TSP-1 is a glycoprotein that functions in the biology of bladder cancer. We investigated the relationship between the distribution ofTSP-1-1223 A/G polymorphism (rs2169830) and the clinical characteristics of bladder cancer.Materials and Methods. TaqMan assay was performed to determine the genotype of 609 cases and 670 control subjects in a Chinese population. Logistic regression was used to assess the association between the polymorphism and the risk of bladder cancer. Quantitative real-time polymerase chain reaction was performed to determineTSP-1mRNA expression. Survival curves were generated using the Kaplan-Meier method.Results. No significant differences were detected in the genotype frequencies of healthy control subjects and patients with bladder cancer. By contrast, the time until the first recurrence differed significantly between genotypes (P=0.017). The expression ofTSP-1mRNA in bladder cancer tissues was lower in patients with an AG genotype than in those with an AA genotype. The lowest expression was observed in patients with a GG genotype.Conclusions. In conclusion,TSP-1-1223 A/G polymorphism may contribute to the recurrence of bladder cancer in Chinese population.

scholarly journals NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Ji-sheng Jing ◽  
Hongbo Li ◽  
Shun-cai Wang ◽  
Jiu-ming Ma ◽  
La-qing Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Survival Curve ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Clinicopathological Characteristics ◽  
Pcr Analysis ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
The Relationship

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.

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