scholarly journals The Role of CBLL1 in the Prognosis and Immune Infiltration of Pan-Cancer

2020 ◽  
Author(s):  
Qiang Guo ◽  
Dan Li ◽  
Yanmei Ji ◽  
Jialong Guo

Abstract ObjectiveThis study aims to explore the role of CBLL1 in pan-carcinoma and tumor immune infiltrates. MethodsDownload mRNA expression, mutation and clinical data in UCSC database, to analyze the relationship between CBLL1 expression and clinicopathological vlaue, and immune microenvironment in pan-cancer. CIBERSORT was used to analyze the relationship between CBLL1 expression and the infiltration of pan-carcinoma immune cells. The mRNA expression data of UCSC database were used to analyze the correlation between CBLL1 expression and pan-cancer immunomodulations, checkpoints and receptor molecules. ResultsThe levels of CBLL1 mRNA expression in pan-cancer tissues were abnormal. The level of CBLL1 is related to the age, race, clinical stage and treatment effect of patients with pan-carcinoma and associated with the prognosis of patients with KIRC, LUSC, THCA, THYM, MESO, PRAD, STAD, and UVM. Univariate COX regression analysis showed that expression of CBLL1 was a risk factor for poor prognosis in patients with KICH, KIRC, LAML, THYM, KIRC, PCPG, OV, PRAD, STAD, GBM and UVM. The expression level of CBLL1 was correlated with BLCA, BRCA, COAD, LAML, LGG, LUAD, LUSC, SARC, STAD, THCA, THYM and UVM tumor mutational burden, and with ACC, BRCA, CESC, COAD, DLBC, HNSC, PRAD, READ, SARC, STAD, TGCT, THCA and UCEC microsatellite instability. The expression level of CBLL1 was correlated with cancer stromal cells and immune cells. The expression of CBLL1 is related to pan-cancer immunomodulators, checkpoints and receptor molecules. ConclusionCBLL1 is abnormally expressed in patients with pan-carcinoma, which is expected to be a biomarker for prognosis, mutation and immune infiltration in patients with pan-carcinoma.

2020 ◽  
Author(s):  
Qiang Guo ◽  
Dan Li ◽  
Yan-Mei Ji ◽  
Jialong Guo

Abstract Background The modification of N6-methyladenosine (m6A) plays an important role in physiology and disease progression. The relationship between the role of m6a-related gene CBLL1 in pan-carcinoma and tumor immune infiltrates has remained unknown. Methods To explore the expression level of CBLL1 methylation in pan-cancer in SMART database, and download mRNA expression, mutation and clinical data in UCSC database, to analyze the expression level of CBLL1, and the relationship between CBLL1 expression and clinicopathological features, prognosis, mutation and immune microenvironment in pan-cancer. CIBERSORT was used to analyze the relationship between the expression of CBLL1 and the infiltration of pan-carcinoma immune cells. The mRNA expression data of UCSC database were used to analyze the correlation between CBLL1 expression and pan-cancer immunomodulations, checkpoints and receptor molecules. Gene Set enrichment analysis (GSEA) revealed the possible mechanism of CBLL1 in the regulation of pan-cancer progression. Results The levels of CBLL1 methylation and mRNA expression in pan-cancer tissues were abnormal. The level of CBLL1 is related to the age, race, clinical stage and treatment effect of patients with pan-carcinoma and associated with the prognosis of patients with KIRC, LUSC, THCA, THYM, MESO, PRAD, STAD, and UVM. Univariate COX regression analysis showed that expression of CBLL1 was a risk factor for poor prognosis in patients with KICH, KIRC, LAML, THYM, KIRC, PCPG, OV, PRAD, STAD, GBM and UVM.The expression level of CBLL1 was correlated with BLCA, BRCA, COAD, LAML, LGG, LUAD, LUSC, SARC, STAD, THCA, THYM and UVM tumor mutational burden (TMB), and with ACC, BRCA, CESC, COAD, DLBC, HNSC, PRAD, READ, SARC, STAD, TGCT, THCA and UCEC microsatellite instability (MSI). The expression level of CBLL1 was correlated with pan-cancer stromal cells and immune cells. The expression of CBLL1 is related to pan-cancer immunomodulators, checkpoints and receptor molecules. GSEA found that CBLL1 may participate in the progression of pan-cancer through B cell receptor singaling pathway, mRNA binding, immunoglobulin receptor binding, Positive Regulation of cell cycle phase transition and other mechanisms. Conclusions CBLL1 is abnormally expressed in patients with pan-carcinoma, which is expected to be a biomarker for prognosis, mutation and immune infiltration in patients with pan-carcinoma.


2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Xiaodong Chen ◽  
Fen Tian ◽  
Peng Lun ◽  
Yugong Feng

Abstract Tumor-infiltrating immune cells play a decisive part in prognosis and survival. Until now, previous researches have not made clear about the diversity of cell types involved in the immune response. The objective of this work was to confirm the composition of tumor-infiltrating immune cells and their correlation with prognosis in meningiomas based on a metagene approach (known as CIBERSORT) and online databases. A total of 22 tumor-infiltrating immune cells were detected to determine the relationship between the immune infiltration pattern and survival. The proportion of M2 macrophages was more abundant in 68 samples, reaching more than 36%. Univariate Cox regression analysis displayed that the proportion of dendritic cells was obviously related to prognosis. Hierarchical clustering analysis identified two clusters by the method of within sum of squares errors, which exhibited different infiltrating immune cell composition and survival. To summarize, our results indicated that proportions of tumor-infiltrating immune cells as well as cluster patterns were associated with the prognosis, which offered clinical significance for research of meningiomas.


2022 ◽  
Vol 8 ◽  
Author(s):  
Fei Chen ◽  
Yumei Fan ◽  
Xiaopeng Liu ◽  
Jianhua Zhang ◽  
Yanan Shang ◽  
...  

Heat shock factor 2 (HSF2), a transcription factor, plays significant roles in corticogenesis and spermatogenesis by regulating various target genes and signaling pathways. However, its expression, clinical significance and correlation with tumor-infiltrating immune cells across cancers have rarely been explored. In the present study, we comprehensively investigated the expression dysregulation and prognostic significance of HSF2, and the relationship with clinicopathological parameters and immune infiltration across cancers. The mRNA expression status of HSF2 was analyzed by TCGA, GTEx, and CCLE. Kaplan-Meier analysis and Cox regression were applied to explore the prognostic significance of HSF2 in different cancers. The relationship between HSF2 expression and DNA methylation, immune infiltration of different immune cells, immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI) were analyzed using data directly from the TCGA database. HSF2 expression was dysregulated in the human pan-cancer dataset. High expression of HSF2 was associated with poor overall survival (OS) in BRCA, KIRP, LIHC, and MESO but correlated with favorable OS in LAML, KIRC, and PAAD. The results of Cox regression and nomogram analyses revealed that HSF2 was an independent factor for KIRP, ACC, and LIHC prognosis. GO, KEGG, and GSEA results indicated that HSF2 was involved in various oncogenesis- and immunity-related signaling pathways. HSF2 expression was associated with TMB in 9 cancer types and associated with MSI in 5 cancer types, while there was a correlation between HSF2 expression and DNA methylation in 27 types of cancer. Additionally, HSF2 expression was correlated with immune cell infiltration, immune checkpoint genes, and the tumor immune microenvironment in various cancers, indicating that HSF2 could be a potential therapeutic target for immunotherapy. Our findings revealed the important roles of HSF2 across different cancer types.


2021 ◽  
Author(s):  
Fang Liu ◽  
Fengyihuan Fu ◽  
Yuqiang Nie

Abstract Background: LINC00634 is highly expressed in esophageal cancer, and its depletion can suppress the viability and induce the apoptosis of esophageal cancer cells. However, there is a lack of studies that examine the relationship between LINC00634 expression and the clinicopathological features, survival outcomes, prognostic factors and tumor immune cell infiltration of colorectal carcinoma (CRC) patients.Objective: We aim at investigating the role of LINC00634 in colorectal carcinoma.Methods: We obtained data from the TCGA (The Cancer Genome Atlas) public database, GTEx (Genotype-Tissue Expression) database and clinical samples. Wilcoxon rank-sum test, Kruskal-Wallis test and logistic regression analysis were employed to assess the relationship between LINC00634 expression and the clinicopathological characteristics of CRC patients. Receiver operating characteristic (ROC) curve was constructed to evaluate the ability of LINC00634 for distinguishing between CRC patients and normal subjects based on the area under the curve (AUC) score. Univariate and multivariate analyses were conducted to evaluate the association between prognostic factors and survival outcomes. Kaplan-Meier curves and Cox regression analysis were employed to determine the contribution of LINC00634 expression to the prognosis of colorectal carcinoma patients. Immune infiltration analysis and Gene Set Enrichment Analysis (GSEA) were conducted to identify the significantly involved functions of LINC00634. Finally, a nomogram was constructed for internal verification based on the Cox regression data.Results: The expression of LINC00634 was upregulated in CRC patients, and markedly associated with N stage, residual tumor, pathological stage, and overall survival (OS) event. ROC curve showed that LINC00634 had strong diagnostic and prognostic abilities (AUC=0.74). The high expression of LINC00634 could predict poor disease specific survival (DSS; P=0.008) and poor overroll survival (OS;P<0.01). The expression of LINC00634 was independently associated with OS in CRC patients (P=0.019). GSEA and immune infiltration analysis demonstrated that LINC00634 expression was involved in gene transcription, epigenetic regulation and the functions of certain types of immune infiltrating cells. The c-index of the nomogram was 0.772 (95%CI: 0.744-0.799).Conclusions: Our study reveals that LINC00634 can serve as a potential prognostic biomarker for CRC patients.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xin Rui ◽  
Siliang Shao ◽  
Li Wang ◽  
Jiangyong Leng

Abstract Background Some historic breakthroughs have been made in immunotherapy of advanced cancer. However, there is still little research on immunotherapy in prostate cancer. We explored the relationship between immune cell infiltration and prostate cancer recurrence and tried to provide new ideas for the treatment of prostate cancer. Methods Prostate cancer RNA-seq data and clinical information were downloaded from the TCGA database and GEO database. The infiltration of 24 immune cells in tissues was quantified by ssGSEA. Univariate Cox regression analysis was used to screen for immune cell types associated with tumor recurrence, weighted gene co-expression network analysis (WGCNA) and LASSO were used to identify hub genes which regulate prognosis in patients through immune infiltration. Then, the nomogram was constructed based on the hub gene to predict the recurrence of prostate cancer, and the decision curve analysis (DCA) was used to compare the accuracy with the PSA and Gleason prediction models. Result Analysis showed that Th2 cells and Tcm related to prostate cancer recurrence after radical prostatectomy, and they are independent protective factors for recurrence. Through WGCNA and Lasso, we identified that NDUFA13, UQCR11, and USP34 involved in the infiltration of Th2 cells and Tcm in tumor tissues, and the expression of genes is related to the recurrence of patients. Based on the above findings, we constructed a clinical prediction model and mapped a nomogram, which has better sensitivity and specificity for prostate cancer recurrence prediction, and performed better in comparison with PSA and Gleason’s predictions. Conclusion The immune cells Th2 cells and Tcm are associated with recurrence of PCa. Moreover, the genes NDUFA13, UQCR11, and USP34 may affect the recurrence of PCa by affecting the infiltration of Th2 cells and Tcm. Moreover, nomogram can make prediction effectively.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Song Wang ◽  
Xueyou Ma ◽  
Yufan Ying ◽  
Jiazhu Sun ◽  
Zitong Yang ◽  
...  

Abstract Background Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) is a member of the PAS superfamily. Previous studies explored the carcinogenic roles of transcription factor ARNTL2 in human malignancies. However, its roles in ccRCC have not been elucidated. This study sought to explore the roles of ARNTL2 in ccRCC and determine its correlations with tumor immunity. Methods The expression of ARNTL2 was analyzed using the GEO, TCGA and GTEx database, and verified in ccRCC tissue samples and cell lines by qRT-PCR and western blot analysis. Kaplan–Meier survival curve analysis, Cox regression analysis (including univariate and multivariate analysis) was utilized to evaluate the prognostic values of ARNTL2. Potential biological mechanisms of ARNTL2 were explored using GSEA method. Colony formation and wound healing assays were conducted to explore the oncogenic role of ARNTL2 in ccRCC. ssGSEA and xCell algorithm were used to explore the correlation between ARNTL2 expression and tumor immune microenvironment (TIME). Results ARNTL2 was significantly upregulated in ccRCC tissues and cell lines compared to normal kidney tissues and cell line. Enhanced expression of ARNTL2 was strongly linked to advanced clinical stage and unfavorable overall survival in ccRCC. ARNTL2 was determined as an independent prognostic marker through cox regression analysis. A prognostic nomogram was constructed to predict 1-, 3- and 5-year overall survival of ccRCC patients by integrating ARNTL2 expression with other clinicopathologic variables. GSEA analysis showed that focal adhesion, T cell receptor, cell cycle, and JAK-STAT signaling pathway were significantly enriched in high ARNTL2 samples. Silencing of ARNTL2 suppressed the colony formation ability and wound healing efficacy of ccRCC cell lines. xCell analysis showed that high expression level of ARNTL2 exhibited an immune infiltration status similar to CD8 + inflamed ccRCC subtype, which was characterized by high infiltration level of CD8 + T cell and high expression level of the immune escape biomarkers such as PD-L1, PD-L2, PD1 and CTLA4. Conclusion ARNTL2 is an independent adverse predictor of ccRCC patient survival. High expression level of ARNTL2 is associated with immune infiltration, and may be a novel therapeutic target in ccRCC.


2021 ◽  
Vol 10 ◽  
Author(s):  
Jun Liu ◽  
Shanqiang Zhang ◽  
Wenjie Dai ◽  
Chongwei Xie ◽  
Ji-Cheng Li

SLC41A3, as a member of the 41st family of solute carriers, participates in the transport of magnesium. The role of SLC41A3 in cancer prognosis and immune regulation has rarely been reported. This study was designed to analyze the expression status and prognostic significance of SLC41A3 in pan-cancers. The mRNA expression profiles of SLC41A3 were obtained from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), the Broad Institute Cancer Cell Line Encyclopedia (CCLE), and the International Cancer Genome Consortium (ICGC). The Cox regression and Kaplan-Meier analyses were used to evaluate the prognostic value of SLC41A3 in pan-cancer. Furthermore, the correlation between SLC41A3 expression and immune cells infiltration, immune checkpoint, mismatch repair (MMR), DNA methyltransferase (DNMT), tumor mutation burden (TMB), and microsatellite instability (MSI) were calculated using data form TCGA database. The results showed that the expression of SLC41A3 was down-regulated in kidney renal clear cell carcinoma (KIRC), and was associated with poor overall survival and tumor-specific mortality. Whereas, the expression of SLC41A3 was up-regulated in liver hepatocellular carcinoma (LIHC), and the results of Cox regression analysis revealed that SLC41A3 was an independent factor for LIHC prognosis. Meanwhile, a nomogram including SLC41A3 and stage was built and exhibited good predictive power for the overall survival of LIHC patients. Additionally, correlation analysis suggested a significant correlation between SLC41A3 and TMB, MSI, MMR, DNMT, and immune cells infiltration in various cancers. The overall survival and disease-specific survival analysis revealed that the combined SLC41A3 expression and immune cell score, TMB, and MSI were significantly associated with clinical outcomes in ACC, LIHC, and UVM patients. Therefore, we proposed that SLC41A3 may serve as a potential prognostic biomarker for cancer.


2021 ◽  
Author(s):  
Aitao Nai ◽  
SHOAIB BASHIR ◽  
Ling Jin ◽  
Zirui He ◽  
Shuwen Zeng ◽  
...  

Abstract Background: Interleukin-11 receptor subunit alpha (IL-11RA) contributes to multiple biological processes in various tumors. However, the role of IL-11RA in Lung adenocarcinoma (LUAD) is still undetermined. The study aims to explore the role of IL-11RA in LUAD via an integrated bioinformatics analysis. Methods: TIMER, GEPIA, TCGA and HPA databases analysis were used to detect IL-11RA expression. UALCAN database was used to analysis the correlation between IL-11RA expression and clinicopathological parameters of LUAD. Kaplan-Meier Plotter, TCGA and GEO databases were used to analysis overall survival (OS) and progression-free survival (PFS) of the LUAD patients. Univariate Cox regression analysis was used to assess the prognostic value of IL-11RA in different clinical characteristics. GSEA, and TIMER were used to investigate the relationship between IL-11RA and immune infiltration.Results: The expression of IL-11RA was down-regulated in LUAD tissues. Furthermore, IL-11RA expression was closely associated with clinical stage, lymph node stage and smoking habits. The patients with lower IL-11RA expression had poorer overall survival (OS) and progression-free survival (PFS). Lower IL-11RA expression was significantly associated with its hypermethylation, and the hypermethylation of CpG site at cg14609668 and cg21504624 was obviously correlated with poorer OS. Then, we found that IL-11RA may play an important role in LUAD progression and immune regulations. Notably, High expression of IL-11RA may suppress the progression of LUAD through inhibiting cell proliferation and immune cell infiltration, especially in B cells, CD4+ T cells, and Dendritic Cell. Conclusions: Decreased IL-11RA expression correlates with poor prognosis and immune infiltration in LUAD. Our work highlights IL-11RA might be a potential biomarker for prognosis and provide a new therapeutic target for LUAD patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fei Peng ◽  
Si Lei ◽  
Quan Zhang ◽  
Yanjun Zhong ◽  
Shangjie Wu

BackgroundCigarette smoking has been proven to be a risk factor in the development of many diseases. However, it remains controversial with respect to the relationship of smoking with COVID-19. The purpose of this study was to explore the role of smoking in COVID-19.MethodsA total of 622 patients with COVID-19 in China were enrolled in the study. Corresponding clinical and laboratory data were collected and analyzed. Meanwhile, Kaplan-Meier curve and Cox regression analysis were employed to analyze the association of smoking with survival in patients with COVID-19.ResultsSmoking was statistically significant comparing non-survivors and survivors of patients with COVID-19 (P = 0.007). Males had higher proportion of smoking than females (91.9% vs. 8.1%, P &lt; 0.001). Compared with the non-smoker, there was significant statistical difference in the incidence of cerebrovascular disease in smoking patients with COVID-19 (9.7% vs. 3.4%, P = 0.017). White blood cell count (6.3 vs. 5.4; P = 0.037), hemoglobin level (139.0 vs. 127.0; P &lt; 0.001), and creatinine level (77.3 vs. 61.0; P &lt; 0.001) were significantly increased in COVID-19 patients who smoked. Moreover, smoking patients showed a worse survival compared with non-smoking patients (Log Rank P = 0.045). After adjustment for age, gender and underlying diseases, patients with smoking still had higher risk of mortality than that of non-smoking patients (hazard ratio[HR] 1.897, 95% confidence interval [CI]1.058–3.402, P = 0.032).ConclusionSmoking was thought to be a risk factor in predicting the prognosis of COVID-19 and smoking patients might have a higher risk of mortality than that of the non-smoking patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rehan Khan ◽  
Ananya Palo ◽  
Manjusha Dixit

AbstractFRG1 has a role in tumorigenesis and angiogenesis. Our preliminary analysis showed that FRG1 mRNA expression is associated with overall survival (OS) in certain cancers, but the effect varies. In cervix and gastric cancers, we found a clear difference in the OS between the low and high FRG1 mRNA expression groups, but the difference was not prominent in breast, lung, and liver cancers. We hypothesized that FRG1 expression level could affect the functionality of the correlated genes or vice versa, which might mask the effect of a single gene on the OS analysis in cancer patients. We used the multivariate Cox regression, risk score, and Kaplan Meier analyses to determine OS in a multigene model. STRING, Cytoscape, HIPPIE, Gene Ontology, and DAVID (KEGG) were used to deduce FRG1 associated pathways. In breast, lung, and liver cancers, we found a distinct difference in the OS between the low and high FRG1 mRNA expression groups in the multigene model, suggesting an independent role of FRG1 in survival. Risk scores were calculated based upon regression coefficients in the multigene model. Low and high-risk score groups showed a significant difference in the FRG1 mRNA expression level and OS. HPF1, RPL34, and EXOSC9 were the most common genes present in FRG1 associated pathways across the cancer types. Validation of the effect of FRG1 mRNA expression level on these genes by qRT-PCR supports that FRG1 might be an upstream regulator of their expression. These genes may have multiple regulators, which also affect their expression, leading to the masking effect in the survival analysis. In conclusion, our study highlights the role of FRG1 in the survivability of cancer patients in tissue-specific manner and the use of multigene models in prognosis.


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