scholarly journals Pan-Cancer Analysis of the Associations of TGFBI Expression With Prognosis and Immune Characteristics

2021 ◽  
Vol 8 ◽  
Author(s):  
Yun Chen ◽  
Han Zhao ◽  
Yao Feng ◽  
Qin Ye ◽  
Jing Hu ◽  
...  

Transforming growth factor-beta-induced (TGFBI) protein has important roles in tumor growth, metastasis, and immunity. However, there is currently no pan-cancer evidence regarding TGFBI. In this study, we conducted a pan-cancer analysis of TGFBI mRNA and protein expression and prognoses of various cancer types using public databases. We also investigated the associations of TGFBI expression with tumor microenvironment (TME) components, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI), along with the TGFBI genetic alteration types. The results showed that TGFBI expression varied among different cancer types, and it was positively or negatively related to prognosis in various cancers. TGFBI expression was also significantly correlated with TME components, TMB, MSI, immune cell infiltration, and immunoinhibitory and immunostimulatory gene subsets. These findings indicate that TGFBI participates in various immune responses and it may function as a prognostic marker in various cancers. The findings may be useful for developing immunotherapies that target TGFBI.

2021 ◽  
Author(s):  
Sha Li ◽  
Yaqiong Liu ◽  
Chaoling Yao ◽  
Anji Xu ◽  
Xiaoling Zeng ◽  
...  

Abstract Background: Nuclear receptor binding SET domain protein-3 (NSD3) has been reported to be a crucial regulator of carcinogenesis as a histone lysine methyltransferase in multiple cancer types. However, the underlying mechanisms have not been clearly delineated. Therefore, we aimed to investigate the expression pattern, prognostic value, and potential function of NSD3 in 33 types of human cancer. Methods: The potential roles of NSD3 were explored using datasets from The Cancer Genome Atlas (TCGA) pan-cancer dataset and an array of bioinformatics methods, including analyses of the relationship between NSD3 expression and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA amplification, and immune cell infiltration across 33 cancer types. Results: Many types of cancers are characterized according to the dysregulation of NSD3, which is associated with the pathological stage of cancer. Patients in our study with higher NDS3 levels, which were attributed to NSD3 copy number amplification, always experienced shorter survival periods. Additionally, NSD3 expression was associated with TMB and MSI in 10 different cancer types. The top five cancers whose NSD3 expression correlated with immune scores were further analyzed. The levels of immune-cell infiltration differed significantly between high and low NSD3-expressing samples in each of the five cancer types. Functional enrichment of the NSD3 co-expressed genes indicated a role for NSD3 in the regulation of immune responses and tumorigenesis. Conclusions: Our study revealed that NSD3 can function as a prognostic marker in various cancers due to its role in tumorigenesis and tumor immunity.


2021 ◽  
Author(s):  
Kuangxun Li ◽  
Junzhe Liu ◽  
Xinyu Yang ◽  
Zewei Tu ◽  
Kai Huang ◽  
...  

Background: THUMPD1 is a specific RNA adaptor that assists acetylation of mRNA and production of N4-acetylcytidine (ac4C). However, it remains unclear whether THUMPD1 plays a part in tumorigenesis and therapeutic efficacy. Here, we analyzed the expression profiles and prognostic value of THUMPD1 in pan-cancer and gained insights into the correlation between THUMPD1 expression level and immunotherapy efficacy. Methods: Gene expression pattern and its correlation with prognosis, immune cell infiltration in pan-cancer were obtained from GTEx, CCLE and TCGA databases, with Kaplan-Meier method and Spearman correlation analysis used. Western blotting and immunofluorescence on clinical samples was performed to validate our database-derived results. Correlation between THUMPD1 expression level and immunotherapy responses was also explored, based on clinical cohorts receiving PD-L1 antibody therapy. Finally, GSEA was performed to show the possible tumorigenic mechanism. Results: THUMPD1 was highly expressed in most cancer types, and this elevated expression indicated poor or improved prognosis for different cancers. In kidney renal clear cell carcinoma (KIRC) and rectum adenocarcinoma (READ), patients with higher THUMPD1 expression exhibited a better prognosis, while liver hepatocellular carcinoma (LIHC) patients had worse prognosis. Besides, THUMPD1 was significantly associated with immune cell infiltration, tumor mutation burden (TMB), microsatellite instability (MSI),immune checkpoints and neoantigen in many cancer types. Further, more clinical advantages and therapeutic responses were observed in patients with high THUMPD1 expression. Conclusions: THUMPD1 may serve as a novel predictor to evaluate cancer prognosis and immune therapy efficacy in diverse cancer types.


1997 ◽  
Vol 158 (6) ◽  
pp. 2284-2290 ◽  
Author(s):  
Ahmed I. El-Sakka ◽  
Howayda M. Hassoba ◽  
Richard M. Chui ◽  
Rajendra S. Bhatnagar ◽  
Rajvir Dahiya ◽  
...  

2019 ◽  
Vol 14 ◽  
pp. 80-89 ◽  
Author(s):  
Xiang An ◽  
Yuanyuan Zhu ◽  
Tongsen Zheng ◽  
Guangyu Wang ◽  
Minghui Zhang ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Junhan Zhou ◽  
Wenxiao Jiang ◽  
Wenbin Huang ◽  
Miaomiao Ye ◽  
Xueqiong Zhu

Purpose. To explore the potential role of the transforming growth factor-beta (TGF-β) subtypes in the prognosis of ovarian cancer patients. Materials and Methods. The prognostic roles of individual TGF-β subtypes in women with ovarian cancer were retrieved from the Kaplan-Meier plotter (KM plotter) database. In addition, the Oncomine database and immunohistochemistry were used to observe the mRNA and protein expression of TGF-β subtypes between human ovarian carcinoma and normal ovarian samples, respectively. Results. TGF-β1 and TGF-β4 were totally uncorrelated with survival outcomes in women with ovarian cancer. Increased TGF-β2 and TGF-β3 mRNA expression was markedly related to unfavorable prognosis, especially in women with serous, poorly differentiated, and late-stage ovarian carcinoma. High expression levels of TGF-β2 were related to worse progression-free survival (PFS) while TGF-β3 was linked to unfavorable overall survival (OS) and PFS in women with TP53-mutated ovarian cancer. TGF-β2 was associated with poor OS and PFS from treatment with chemotherapy with platins, Taxol, or a platin+Taxol. However, overexpression of TGF-β3 was associated with poor OS from the use of platins and poor PFS of Taxol or a platin+Taxol in women with ovarian carcinoma. Furthermore, the expression of TGF-β2 mRNA and protein was higher but only TGF-β3 mRNA expression was higher in cancerous tissues than in normal ovarian samples. Conclusion. Higher expression of TGF-β2 functioned as a significant predictor of poor prognosis in women with ovarian cancer, especially those with TP53 mutations or who were undergoing chemotherapy with platins, Taxol, or a platin+Taxol.


Author(s):  
Qi Zhao ◽  
Junfeng Liu

Objective: Prolyl 4-hydroxylase, alpha polypeptide I (P4HA1), a key enzyme in collagen synthesis, comprises two identical alpha subunits and two beta subunits. However, the immunomodulatory role of P4HA1 in tumor immune microenvironment (TIME) remains unclear. This study aimed to evaluate the prognostic value of P4HA1 in pan-cancer and explore the relationship between P4HA1 expression and TIME.Methods: P4HA1 expression, clinical features, mutations, DNA methylation, copy number alteration, and prognostic value in pan-cancer were investigated using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression data. Pathway enrichment analysis of P4HA1 was performed using R package “clusterProfiler.” The correlation between immune cell infiltration level and P4HA1 expression was analyzed using three sources of immune cell infiltration data, including ImmuCellAI database, TIMER2 database, and a published work.Results: P4HA1 was substantially overexpressed in most cancer types. P4HA1 overexpression was associated with poor survival in patients. Additionally, we discovered that P4HA1 expression was positively associated with infiltration levels of immunosuppressive cells, such as tumor-associated macrophages, cancer-associated fibroblasts, nTregs, and iTregs, and negatively correlated with CD8+ T and NK cells in pan-cancer.Conclusions: Our results highlighted that P4HA1 might serve as a potential prognostic biomarker in pan-cancer. P4HA1 overexpression is indicative of an immunosuppressive microenvironment. P4HA1 may be a potential target of immunotherapy.


2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Haizhou Ji ◽  
Mi Ren ◽  
Tongyu Liu ◽  
Yang Sun

Objective. Uncovering genetic and immunologic tumor features is critical to gain insights into the mechanisms of immunotherapeutic response. Herein, this study observed the functions of CXCR2 in prognosis and immunology of ovarian cancer. Methods. Expression, prognostic significance, and genetic mutations of CXCR2 were analyzed in diverse cancer types based on TCGA and GTEx datasets. Associations of CXCR2 expression with immune checkpoints, neoantigens, tumor mutational burden (TMB), and microsatellite instability (MSI) were evaluated across pancancer. CXCR2-relevant genes were identified, and their biological functions were investigated in ovarian cancer. Through three algorithms (TIMER, quanTIseq, and xCell), we assessed the relationships of CXCR2 with immune cell infiltration in ovarian cancer. GSEA was adopted for inferring KEGG and hallmark pathways involved in CXCR2. Results. CXCR2 presented abnormal expression in tumors than paired normal tissues across pancancer. Higher expression of CXCR2 was found in ovarian cancer. Moreover, its expression was in relation to overall survival and progression including ovarian cancer. Prominent associations of CXCR2 with immune checkpoints, neoantigens, TMB, and MSI were observed in human cancers. Somatic mutations of CXCR2 frequently occurred across pancancer. Amplification was the main mutational type of CXCR2 in ovarian cancer. CXCR2-relevant genes were markedly enriched in immunity activation and carcinogenic pathways in ovarian cancer. Moreover, it participated in modulating immune cell infiltration in the tumor microenvironment of ovarian cancer such as macrophage and immune response was prominently modulated by CXCR2. Conclusion. Collectively, CXCR2 acts as a promising prognostic and immunological biomarker as well as a novel immunotherapeutic target of ovarian cancer.


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