Prognostic and immunological role of Fam20C in pan-cancer

Abstract Background: The family with sequence similarity 20-member C (Fam20C) kinase plays important roles in physiopathological process and is responsible for majority of the secreted phosphoproteome, including substrates associated with tumor cell migration. However, it remains unclear whether Fam20C plays a role in cancers. Here, we aimed to analyze the expression and prognostic value of Fam20C in pan-cancer and to gain insights into the association between Fam20C and immune infiltration. Methods: We analyzed Fam20C expression patterns and the associations between Fam20C expression levels and prognosis in pan-cancer via the ONCOMINE, TIMER (Tumor Immune Estimation Resource), PrognoScan, GEPIA (Gene Expression Profiling Interactive Analysis), and Kaplan–Meier Plotter databases. After that, GEPIA and TIMER databases were applied to investigate the relations between Fam20C expression and immune infiltration across different cancer types, especially BLCA (bladder urothelial carcinoma), LGG (brain lower grade glioma), and STAD (stomach adenocarcinoma). Results: Compared with adjacent normal tissues, Fam20C was widely expressed across many cancers. In general, Fam20C showed a detrimental role in pan-cancer, it was positively associated with poor survival of BLCA, LGG, and STAD patients. Specifically, based on TCGA (The Cancer Genome Atlas) database, a high expression level of Fam20C was associated with worse prognostic value in stages T2–T4 and stages N0–N2 in the cohort of STAD patients. Moreover, Fam20C expression had positive associations with immune infiltration, including CD4+ T cells, macrophages, neutrophils, and dendritic cells, and other diverse immune cells in BLCA, LGG, and STAD. Conclusion: Fam20C may serve as a promising prognostic biomarker in pan-cancer and has positive associations with immune infiltrates.

Download Full-text

Predicting STAT1 as a prognostic marker in patients with solid cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920917558 ◽

2020 ◽

Vol 12 ◽

pp. 175883592091755

Author(s):

Jinguo Zhang ◽

Fanchen Wang ◽

Fangran Liu ◽

Guoxiong Xu

Keyword(s):

Ovarian Cancer ◽

Prognostic Value ◽

Renal Carcinoma ◽

The Cancer Genome Atlas ◽

Solid Cancer ◽

Lower Grade ◽

High Grade ◽

Large Tumor ◽

Normal Tissues ◽

Tumor Types

Background: Aberrant activities of signal transducer and activator of transcription 1 (STAT1) have been implicated in cancer development. However, the prognostic value of STAT1 remains unclear. This report identified the role of STAT1 in prognosis in patients with solid cancer through open literature and The Cancer Genome Atlas (TCGA) database. Methods: Published articles were obtained from PubMed, Web of Science, and Embase databases according to a search strategy up to October 2019. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to assess the prognostic factors of patients. TCGA datasets were used to explore the prognostic value of STAT1 in various cancers. Results: A total of 15 studies incorporating 2839 patients with solid cancers were included. Pooled data showed that overexpressed STAT1 favored long overall survival (OS) (HR = 0.604, 95% CI = 0.431–0.846, p = 0.003) and disease-specific survival (DSS) (HR = 0.650, 95% CI = 0.512–0.825, p = 0.000). In subgroup analyses, highly expressed STAT1 was correlated with long OS of patients with high-grade serous ovarian cancer and oral squamous cell carcinoma. Data extracted from TCGA datasets unveiled that STAT1 expression was significantly higher in 12 cancers (e.g. bladder and breast) than their adjacent normal tissues. Again, highly expressed STAT1 favored long OS of patients with ovarian cancer as well as rectum adenocarcinoma, sarcoma, and skin cutaneous melanoma. However, in renal carcinoma, brain lower grade glioma, lung adenocarcinoma, and pancreatic cancer, highly expressed STAT1 was correlated with poor OS of patients. Particularly in renal carcinoma, increased STAT1 expression was associated with high grade, later stage, large tumor size, and lymph node and distant metastasis. Conclusion: STAT1 has been identified to have prognostic value in patients with solid cancer. Highly expressed STAT1 may predict prognosis in cancer patients based on their tumor types.

Download Full-text

Prognosis and immune function of Synaptotagmin-4 in gastric cancer and brain low-grade glioma

10.21203/rs.3.rs-21652/v1 ◽

2020 ◽

Author(s):

Siyuan Jiang ◽

Lizhe Zhu ◽

Chao Jiang ◽

Shibo Yu ◽

Bin Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Immune Function ◽

Treg Cells ◽

Low Grade Glioma ◽

Low Grade ◽

Lower Grade ◽

Expression Levels ◽

Immune Infiltration ◽

Normal Tissues ◽

Kaplan Meier

Abstract Background Synaptotagmins (SYTs) are a family of proteins whose primary feature is the calcium sensor in vesicle transport and exocytosis. SYT4 is one of them, but the relationship between SYT4 and cancer remains unclear. We aim to explore the prognosis and immune function of SYT4 in gastric cancer and low-grade glioma. Methods These databases were used to study the immunological and prognostic role of SYT4 in cancers, including the Oncomine database, Kaplan-Meier plotter, GEPIA2, TIMER, and CGGA. Results The study suggested that the expression levels of SYT4 were lower in both gastric cancer and glioma, compared to the normal tissues. And SYT4 played a protective and harmful role in low-grade gliomas and gastric cancer, respectively. Moreover, we found that a difference between SYT4 expression and the levels of immune infiltration in stomach adenocarcinoma (STAD) and brain lower-grade glioma (LGG). Besides, after exploring the association between the expression levels of SYT4 and markers of immune cells in these two cancers, we found that markers of monocytes, M1/ M2, tumor-associated macrophages (TAMs), Treg cells and SYT4 expressions had an opposite correlation in STAD and LGG. Conclusions SYT4 had an effect on the prognosis of gastric cancer and glioma patients and was related to immune infiltration by regulating TAMs and Treg cells. SYT4 can be used as a prognostic biomarker for STAD and LGG.

Download Full-text

Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research?

Frontiers in Oncology ◽

10.3389/fonc.2021.630417 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chuanxi Yang ◽

Tingting Wu ◽

Jing Zhang ◽

Jinhui Liu ◽

Kun Zhao ◽

...

Keyword(s):

T Cells ◽

Cell Carcinoma ◽

Marker Gene ◽

Gene Marker ◽

Immune Infiltration ◽

Normal Tissues ◽

Kaplan Meier ◽

Positive Correlations ◽

Liver Hepatocellular Carcinoma ◽

Pan Cancer

BackgroundNAT10 (also known as human N-acetyltransferase-like protein) is a critical gene that regulates N4-acetylcytidine formation in RNA, similar to the multiple regulators of N6-methyladenosine. However, the underlying functions and mechanisms of NAT10 in tumor progression and immunology are unclear.MethodsIn this study, we systematically analyzed the pan-cancer expression and correlations of NAT10, using databases including Oncomine, PrognoScan, GEPIA2, and Kaplan-Meier Plotter. The potential correlations of NAT10 with immune infiltration stages and gene marker sets were analyzed using the Tumor Immune Estimation Resource and GEPIA2.ResultsCompared with normal tissues, NAT10 showed higher expression in most cancers based on combined data from TCGA and GTEx. In different datasets, high NAT10 expression was significantly correlated with poor prognosis in adrenocortical carcinoma, head and neck squamous cell carcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and pheochromocytoma and paraganglioma. Moreover, there were significant positive correlations between NAT10 expression and immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, endothelial cells, and fibroblasts in LIHC. NAT10 expression showed strong correlations with diverse immune marker gene sets in LIHC.ConclusionNAT10 expression affects the prognosis of pan-cancer patients and is significantly correlated with tumor immune infiltration. Furthermore, it represents a potential target for cancer therapy.

Download Full-text

Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research?

10.21203/rs.3.rs-94029/v1 ◽

2020 ◽

Author(s):

Chuanxi Yang ◽

Tingting Wu ◽

Jing Zhang ◽

Jinghui Liu ◽

Kun Zhao ◽

...

Keyword(s):

T Cells ◽

Cell Carcinoma ◽

Marker Gene ◽

Gene Marker ◽

Immune Infiltration ◽

Normal Tissues ◽

Kaplan Meier ◽

Positive Correlations ◽

Liver Hepatocellular Carcinoma ◽

Pan Cancer

Abstract BackgroundNAT10 (also known as human N-acetyltransferase-like protein) is a critical gene that regulates N4-acetylcytidine formation in RNA, similar to the multiple regulators of N6-methyladenosine. However, the underlying functions and mechanisms of NAT10 in tumor progression and immunology are unclear.MethodsIn this study, we systematically analyzed the pan-cancer expression and correlations of NAT10, using databases including Oncomine, PrognoScan, GEPIA, and Kaplan-Meier Plotter. The potential correlations of NAT10 with immune infiltration stages and gene marker sets were analyzed using the Tumor Immune Estimation Resource and GEPIA.ResultsCompared with normal tissues, NAT10 showed higher expression in 26 of 27 cancers based on combined data from TCGA and GTEx. In different datasets, high NAT10 expression was significantly correlated with poor prognosis in adrenocortical carcinoma, head and neck squamous cell carcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and pheochromocytoma and paraganglioma. Moreover, there were significant positive correlations between NAT10 expression and immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, endothelial cells, and fibroblasts in LIHC. NAT10 expression showed strong correlations with diverse immune marker gene sets in LIHC.ConclusionNAT10 expression affects the prognosis of pan-cancer patients and is significantly correlated with tumor immune infiltration. Furthermore, it represents a potential target for cancer therapy.

Download Full-text

Development and Validation of a Robust Ferroptosis-Related Prognostic Signature to Predict Overall Survival in Clear Cell Renal Cell Carcinoma

10.21203/rs.3.rs-230598/v1 ◽

2021 ◽

Author(s):

Yen-ting Lin ◽

Can-Xuan Li ◽

Jie Chen

Keyword(s):

Overall Survival ◽

Regression Analysis ◽

Roc Curve ◽

Prognostic Value ◽

Cox Regression ◽

Expression Patterns ◽

The Cancer Genome Atlas ◽

Entire Group ◽

Cox Regression Analysis ◽

Kaplan Meier

Abstract Background: Ferroptosis is a novel defined type of programmed cell death (PCD) with widespread functions involved in physical conditions or multiple diseases including malignancies. However, the relationship between ccRCC and ferroptosis-related regulators remains poorly known. Herein, we investigate the prognostic values and potential mechanisms of ferroptosis-related genes (FRGs) in ccRCC.Methods: Ferroptosis-related genes were obtained from FerrDb database, GeneCards database and previously published literatures. The gene expression profile of ferroptosis-related regulators and corresponding clinicopathological information were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed ferroptosis-related genes (DE-FRGs) were screened between ccRCC specimens and noncancerous specimens. Among these genes, prognostic DE-FRGs were identified using univariate COX analysis and LASSO regression analysis. Further multivariate COX regression was employed to identify prognosis-related hub DE-FRGs and establish a prognostic model. Results: We identified seven hub genes (HMGCR, MT1G, BID, EIF4A1, FOXM1, TFAP2C and CHAC1) from the DE-FRGs using univariate Cox regression analysis, LASSO and multivariate Cox regression analysis, and used them to establish a novel clinical predictive model in the TCGA train cohort (n = 374). Subsequently, we assessed the prognostic value of the model. Survival analysis showed that high-risk patients had a reduced overall survival (OS), the time-dependent receiver operating characteristic (ROC) curve analysis confirmed the signature's diagnostic performance. Additionally, multivariate Cox regression analysis suggested that the risk score was an independent prognostic factor. Additionally, we verified the prognostic performance of the risk model in the testing cohort (n=156), and the entire group (n=530) using Kaplan-Meier curve and ROC curve analyses. Functional analysis indicated that several carcinogenic pathways were enriched, and tumor-infiltrating immune cell abundances, and the expression levels of immunosuppressive molecules were different between two risk groups. Finally, external databases (ONCMINE, GEPIA, HPA, Kaplan-Meier plotter and cbioportal) were used to confirm the expression patterns, prognostic value, and genetic mutations of 7 hub FRGs in ccRCC.Conclusions: Collectively, we successfully constructed a novel ferroptosis-related risk signature that was significantly associated with the prognosis of ccRCC.

Download Full-text

Prognostic Value and Immunological Role of MORF4-Related Gene-Binding Protein in Human Cancers

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.703415 ◽

2021 ◽

Vol 9 ◽

Author(s):

Dongqi Chai ◽

Lilong Zhang ◽

Yongjun Guan ◽

Jingping Yuan ◽

Man Li ◽

...

Keyword(s):

Prognostic Value ◽

Binding Protein ◽

Macrophage Infiltration ◽

Lower Grade ◽

Related Gene ◽

Immune Infiltration ◽

Normal Tissues ◽

Human Cancers ◽

The Relationship

MORF4-related gene-binding protein (MRGBP) is the subunit of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. Much of the research indicated an oncogenic role of MRGBP in the development of cancers. However, it is still unknown the role MRGBP plays in human cancers, which deserves further exploration. In this research, the expression profile, prognostic value of MRGBP, and the relationship between MRGBP and immune infiltration were explored in 33 types of cancer. The differences in MRGBP expression in tumor and normal tissues were explored using data from The Cancer Genome Atlas, Gene Expression Omnibus and ONCOMINE. Analysis of the association between MRGBP and prognosis using Kaplan-Meier survival curve and COX analysis. The data of Tumor mutational burden (TMB), microsatellite instability (MSI) from TCGA. The relationship Between MRGBP expression and immunity was analyzed using the ESTIMATE algorithm and CIBERSORT. Furthermore, we explored MRGBP expression and the relationship between MRGBP expression and macrophage infiltration using immunohistochemical analysis in lower grade glioma (LGG). Our results revealed that MRGBP was highly expressed in most cancer tissues compared with normal tissues. Tumors with increased MRGBP expression had a high clinicopathologic stage and poor prognosis. The expression of MRGBP was closely related to the TMB, MSI. We also found a significant negative correlation between MRGBP expression and stromal scores and immune scores in various types of cancer. Furthermore, MRGBP expression was associated with a variety of immune cells including B cells, NK cells, T cells, and macrophages. LGG and LIHC was selected as representative cancer types for further study, the results of immunohistochemistry indicated that the protein levels of MRGBP were significantly elevated in tumor tissues. Moreover, our LIHC data analysis showed that patients with high MRGBP expression were associated with short survival rates and MRGBP was a risk factor to determine OS. Immunohistochemistry also confirmed that M0 macrophage infiltration in the MRGBP-high group significantly increased. In conclusion, these results reveal that MRGBP can serve as a potential prognostic biomarker and it plays an important role in tumor immune infiltration in various tumors, especially in LGG and LIHC.

Download Full-text

Bioinformatics Analysis of ISLR in Pan-Cancer and its Correlation with Tumor Immunity

10.21203/rs.3.rs-970091/v1 ◽

2021 ◽

Author(s):

Cangyuan Zhang ◽

Ziyang Long ◽

Cheng Yan ◽

Mohamed Said Jalloh ◽

Yongkun Fang ◽

...

Keyword(s):

Tumor Immunity ◽

Bioinformatics Analysis ◽

Expression Patterns ◽

Clinical Prognosis ◽

Immune Infiltration ◽

Normal Tissues ◽

Genes Encoding ◽

Predictive Role ◽

Pan Cancer

Abstract Background The protein meflin encoded by ISLR contains a C2-type immunoglobulin (Ig)-like domain and five leucine-rich repeat (LRR) domains. ISLR is known to play a role in a small number of tumors, but its role in most tumors is unknown. The purpose of this study was to analyze the expression and prognosis of ISLR in pan-cancer, as well as its correlation with tumor immunity. Methods We used multiple databases and R software to conduct bioinformatics analysis to explore the predictive role of ISLR in pan-cancer, mainly involving expression patterns, prognosis, and immune infiltration. Results Compared with normal tissues, the expression of ISLR was significantly increased or decreased in most tumors. Moreover, the high expression of ISLR may cause the prognosis of some tumors to become better or worse. ISLR also affects immune infiltration in a variety of tumors, which affects the clinical prognosis. ISLR is also significantly related to TMB and MSI in pan-cancer and is related to genes encoding immune regulatory genes. ISLR also affects various cancer-and immune-related pathways. Conclusions ISLR is differentially expressed in tumors, may regulate TME, affect tumor prognosis, and is expected to become a prognostic biomarker.

Download Full-text

Identification of Flap Endonuclease 1 With Diagnostic and Prognostic Value in Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.603114 ◽

2021 ◽

Vol 11 ◽

Author(s):

Min Wu ◽

Pan Zhang ◽

Penghui Wang ◽

Zhen Fang ◽

Yaqin Zhu

Keyword(s):

Breast Cancer ◽

Prognostic Marker ◽

Prognostic Value ◽

Diagnostic Value ◽

Roc Curve Analysis ◽

Free Survival ◽

Flap Endonuclease 1 ◽

Normal Tissues ◽

Kaplan Meier ◽

Kaplan Meier Plotter

ObjectiveThis study aims to identify the potential value of flap endonuclease 1 (FEN1) as a diagnostic and prognostic marker for breast cancer (BC).MethodsELISA was used to measure serum FEN1 levels and ECLIA for CA153 and CEA levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value. Oncomine and UALCAN databases were used to analyze the differences in FEN1 mRNA and protein expressions. Kaplan-Meier Plotter database was then used to assess the prognostic value.ResultsBioinformatics analysis showed that the FEN1 mRNA and protein levels were significantly higher in BC tissues than in normal tissues. FEN1 was detected in culture medium of BC cell lines and serum FEN1 concentrations were significantly increased in BC patients than in cancer-free individuals. Besides, FEN1 exhibited higher diagnostic accuracy (AUC values>0.800) than CA153 and CEA for distinguishing BC patients, especially early BC, from the healthy and benign groups, or individually. Additionally, serum FEN1 levels were significantly associated with the stage (P=0.001) and lymph invasion (P=0.016), and serum FEN1 levels were increased with the development of BC. Furthermore, serum FEN1 levels were significantly decreased in post-operative patients than in pre-operative patients (P=0.016). Based on the Kaplan-Meier Plotter database, the survival analysis indicated that FEN1 overexpression was associated with poor prognoses for overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival (DMFS) in BC patients.ConclusionFEN1 might be a novel diagnostic and prognostic marker for BC.

Download Full-text

Prognostic value of CLIC3 mRNA overexpression in bladder cancer

PeerJ ◽

10.7717/peerj.8348 ◽

2020 ◽

Vol 8 ◽

pp. e8348

Author(s):

Mei Chen ◽

Shufang Zhang ◽

Xiaohong Wen ◽

Hui Cao ◽

Yuanhui Gao

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Mrna Expression ◽

Prognostic Value ◽

Multivariate Analyses ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Receptor Interaction ◽

Normal Tissues

Background Human intracellular chloride channel 3 (CLIC3) is involved in the development of various cancers, but the expression and prognostic value of CLIC3 mRNA in bladder cancer (BC) remain unclear. Methods The gene expression data and clinical information of CLIC3 were obtained from the Gene Expression Omnibus (GEO) database and verified in the Oncomine and The Cancer Genome Atlas (TCGA) database. The expression of CLIC3 mRNA in BC tissues and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The Kaplan-Meier method was used to analyze the relationship between the expression of CLIC3 mRNA and the prognosis of BC. Cox univariate and multivariate analyses were performed on the overall survival and tumor-specific survival of BC patients. The genes coexpressed with CLIC3 were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). CLIC3-related signal transduction pathways in BC were explored with gene set enrichment analysis (GSEA). Results The expression of CLIC3 mRNA in BC tissues was higher than that in normal tissues (P < 0.01). High CLIC3 mRNA expression was associated with age (P = 0.021) and grade (P = 0.045) in BC patients. High CLIC3 mRNA expression predicted a poor prognosis in BC patients (P < 0.05). Cox univariate and multivariate analyses showed that high CLIC3 mRNA expression was associated with tumor-specific survival in BC patients (P < 0.05). Functional enrichment analyses indicated that CLIC3 may be significantly associated with the cell cycle, focal adhesion, the extracellular matrix (ECM) receptor interaction and the P53 signaling pathway. Conclusions CLIC3 mRNA is highly expressed in BC, and its high expression is related to the adverse clinicopathological factors and prognosis of BC patients. CLIC3 can be used as a biomarker for the prognosis of BC patients.

Download Full-text

The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: a Systematic Review and Meta-analysis

10.21203/rs.3.rs-135089/v1 ◽

2020 ◽

Author(s):

Kai Gan ◽

Yue Gao ◽

KuangZheng Liu ◽

Bin Xu ◽

Ming Chen

Keyword(s):

Bladder Cancer ◽

Clinical Significance ◽

Prognostic Value ◽

Meta Analysis ◽

Growth Factor Receptor ◽

Tumor Stage ◽

The Cancer Genome Atlas ◽

Her2 Expression ◽

Large Tumor ◽

Normal Tissues

Abstract Objective: Human Epidermal Growth Factor Receptor 2 (HER2) is highly expressed in a variety of tumors and associated with patients’ prognosis, but its role in bladder cancer remains unclear. We conducted this meta-analysis to explore the clinical significance and prognostic value of HER2 in bladder cancer and its potentiality as an immunotherapy target.Methods: PubMed was searched for studies published between January 1, 2000 and January 1, 2020. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to investigate the relationship between HER2 and bladder cancer. UALCAN website was used to obtain TCGA (The cancer genome atlas) database.Results: Our study includes 14 articles, 1398 patients. HER2 expression was significantly higher in bladder cancer than in normal tissues. Our meta-analysis results did not reveal any effect of gender on the expression of HER2 levels in bladder cancer patients. However, HER2 expression in male patients was significantly higher than that in women according to TCGA databases. HER2 expression was also associated with carcinoma in situ, multifocal tumors, large tumor size, high tumor stage and grade, lymph node metastases, risk of recurrence and progression, low recurrence-free survival (RFS) rate. HER2 expression status had no effect on overall survival.Conclusions: Our meta-analysis showed that HER2 expression was related to pathological malignancy and poor prognosis in bladder cancer which indicated that it could be used as an effective biomarker and therapeutic target.

Download Full-text