WD repeat domain 6 as a novelty prognostic biomarker correlates with immune infiltration in lung cancer: A preliminary study
Ontology highlight
ABSTRACT: Background
WD repeat domain 6 (WDR6), a novel human WD‐repeat gene, encodes a member of the WD repeat protein family, and its tumorigenic effect has rarely been reported so far. Methods
Our study used Oncomine, TIMER2.0, GEPIA2, Kaplan–Meier plotter, PrognoScan, and TISIDB tools to analyze the differential expression between pan‐cancer, especially lung cancer, and corresponding normal tissue, and further explore the prognostic and immunological role of WDR6 expression. Results
Our results showed WDR6 was lower expressed in lung squamous cell carcinoma than in normal tissue, but WDR6 expression was correlated obviously with clinical stage in Lung adenocarcinoma. The overall survival, first progression, postprogression survival, and Relapse‐free survival of lung cancer patients were longer in the WDR6 high‐expression group than in the low‐expression group. We found the expression of WDR6 significantly correlated with immune molecules, including immunomodulators, lymphocytes, and chemokines in lung cancer. Conclusion
WDR6 can be used as a prognostic marker for lung cancer and is significantly associated with immune cell infiltration. In this study, we first explored the prognostic and immunological role of WD repeat domain 6 (WDR6) on lung cancer based on the public datasets. The results concluded that there is a possible novel prognostic molecular marker for good survival correlated with immune cell infiltration in lung cancer, called WDR6 expression. This study first offers a relatively comprehensive understanding of the oncogenic roles of WDR6 for lung cancer.
SUBMITTER: Lv M
PROVIDER: S-EPMC9382870 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundCD161, encoded by the killer cell lectin-like receptor B1 (KLRB1) gene, exhibits varied roles among different tumors. This study aimed to explore both the potential value of CD161 as a prognostic biomarker for hepatocellular carcinoma (HCC) and its association with immune cell infiltration.MethodsA total of 109 HCC patients who underwent surgery were retrospectively analyzed. Immunohistochemistry, bioinformatic analyses, and statistical measurements were used to investigate the associations between CD161 expression, immune cell infiltration, and clinical outcomes in both public databases and in-house cohorts.ResultsCD161 was highly expressed at both protein and mRNA levels in adjacent normal tissues compared to tumor tissues of HCC patients. Meanwhile, CD161 was enriched in HCC cases characterized by smaller tumor sizes (≤5 cm) and the absence of portal vein tumor thrombus. Individuals with high CD161 expression showed extended overall survival (OS) and relapse free survival (RFS) compared to those with lower CD161 levels. CD161 was identified as an independent prognostic indicator for both OS and RFS. In addition, the enrichment analysis indicated a close correlation between CD161 and immune response, as well as between CD161 and the signaling pathways of cytokines and chemokines, implying its role in immune regulation during cancer development. Specifically, CD161 expression was positively associated with immunomodulators and tumor-infiltrating immune cells, especially CD8+T cells, CD4+T cells, and dendritic cells. Multiple public databases showed that patients with high CD161 expression were more likely to derive benefits from immunotherapy.ConclusionCD161 was identified as a promising prognostic biomarker for HCC, as its expression indicates a favorable prognosis. Additionally, CD161 is closely linked to high infiltration of immune cells, participates in the regulation of the tumor immune microenvironment, and holds promise as a potential biomarker for predicting the efficacy of immunotherapy.
| S-EPMC11925045 | biostudies-literature
Project description:WD repeat domain 43 (WDR43) is a protein component that encodes WD-repeats and is involved in ribosome biogenesis. However, little is known about the role of WDR43 in cancer prognosis and immune modulation. In this study, we analyzed the expression and prognostic significance of WDR43 in pan-cancer using the Cancer Genome Atlas, the Genotype-Tissue Expression, and the Human Protein Atlas. We also examined the differential expression of WDR43 in liver hepatocellular carcinoma (LIHC) and adjacent tissues of 48 patients using immunohistochemistry. Additionally, we investigated the correlation between WDR43 and clinical characteristics, gene alterations, tumor mutation burden, microsatellite instability, mismatch repair, tumor microenvironment, immune infiltrating cells, and immune-related genes using bioinformatics methods. Gene set enrichment analysis was conducted, and potential biological mechanisms were identified. Immunohistochemistry staining showed that WDR43 was overexpressed in LIHC among 48 patients. Upregulation of WDR43 was associated with unfavorable prognosis, including overall survival in various types of cancer such as LIHC, uterine corpus endometrial cancer, head and neck squamous cell carcinoma, and pancreatic adenocarcinoma. Differential expression of WDR43 was significantly correlated with microsatellite instability, mismatch repair, and immune cell infiltration. Gene ontology annotation analysis revealed that these genes were significantly enriched in immune-related functions, including immune response, immune regulation, and signaling pathways. We conducted a thorough investigation of the clinical features, phases of tumor development, immune infiltration, gene mutation, and functional enrichment analysis of WDR43 in various types of cancer. This research offers valuable insight into the significance and function of WDR43 in clinical therapy.
| S-EPMC11296459 | biostudies-literature
Project description:The current prognosis of glioma is unfavorable and effective treatments remain limited. However, bioinformatics has created new opportunities for improving glioma treatment. Research indicates that H2B is involved in the pathological process of cancer. Thus, this study conducted bioinformatic analyses of the H2B gene family to evaluate whether these genes can play a role in predicting prognosis and are associated with immune infiltration. High expression of H2B genes was observed in cholangiocarcinoma, esophageal carcinoma, glioblastoma multiforme (GBM), head and neck squamous cell carcinoma, and other cancers. In addition, a rise in H2B gene expression was correlated with an increase in glioma grade. In the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) database and multiple datasets from the Gene Expression Omnibus (GEO), high expression of H2B gene family members predicted poor prognosis of a variety of tumors including glioma. In particular, high H2BC5, H2BC9, H2BC11, and H2BC21 expression was associated with poor glioma prognosis. H2BC9, H2BC11, and H2BC12 expression were also positively correlated with both immune and stromal scores. Enrichment analysis indicated that H2B family genes may be involved in the pathological process of glioma using various pathways including the cell cycle and immune response. H2B-specific siRNAs were used to verify the role of H2BC5, H2BC9, H2BC11, and H2BC21 expression on cell cycle distribution. In summary, H2BC5, H2BC9, H2BC11, and H2BC21 were independent prognostic indicators of glioma, and H2BC9 and H2BC11 may correlate with tumor immunity.
| S-EPMC9641242 | biostudies-literature
Project description:BackgroundCCND2 expression influences the growth and proliferation of cancer cells and plays a crucial role in immune response of tumor. However, few studies focused on the correlation between CCND2 and lung adenocarcinoma (LUAD) in terms of prognosis and tumor immune infiltration.MethodsOriginal LUAD case data were screened from The Cancer Genome Atlas (TCGA) database. Using R software, we analyzed differently expressed CCND2 between LUAD and adjacent normal tissues. Kaplan-Meier analysis was conducted to determine the relationship between CCND2 expression and the overall survival of LUAD patients, and Cox regression analysis was performed to identify the independently prognostic risk factors for LUAD. Using TIMER (Tumor Immune Estimation Resource) and CIBERSORTx (Cell-type Identification by Estimating Relative Subsets of known RNA Transcripts) databases, the connection between CCND2 expression and LUAD immune infiltration was investigated.ResultsThe level of CCND2 was significantly lower in LUAD than in adjacent normal tissues [adjusted P<0.05 and log2 fold change (FC) =-1.33]. LUAD patients who expressed lower CCND2 had a shorter overall survival (P=0.046) and CCND2 was an independently prognostic risk factor for LUAD [hazard ratio (HR): 0.77, P=0.049]. In LUAD patients, CCND2 expression was positively associated with the levels of B cells (r=0.159, P=4.00e-04), CD8+ T cells (r=0.287, P=7.88e-11), CD4+ T cells (r=0.301, P=8.14e-12), macrophages (r=0.128, P=4.57e-03), neutrophils (r=0.373, P=1.07e-17), and myeloid dendritic cells (r=0.284, P=1.43e-10). The levels of B cells and macrophages had significantly association with the overall survival of LUAD patients. CIBERSORTx showed that the proportions of naive B cells, resting dendritic cells, and macrophages M1 were higher in the low CCND2 expression group (P<0.05); whereas macrophages M1, activated natural killer (NK) cells, and resting CD4+ memory cells were lower (P<0.05).ConclusionsCCND2 can be exploited as a novel prognostic biomarker involved in immune infiltration of LUAD, hence providing new preventative and therapeutic options for LUAD.
| S-EPMC11009805 | biostudies-literature
Project description:Immune evasion in glioma strongly correlates with clinical outcomes; however, the molecular mechanisms driving the maintenance of immunosuppression remain largely unknown. Recently studies demonstrate that Klothos are aberrantly expressed in several cancers and are potential therapeutic targets in cancers. However, their roles are still unclear in glioma. Here, we show that LCTL is highly expressed in gliomas and that its expression is regulated by DNA methylation status at the promoter. LCTL expression is also found to be significantly associated with high tumor aggressiveness and poor outcomes for glioma patients. Mechanistically, results suggested that LCTL might play an important immunosuppressive role by recruiting immunosuppressive cells and regulating tumor-associated macrophages polarization, T cell exhaustion, and epithelial-mesenchymal transition through FGF signaling in glioma. Our results establish LCTL as a key biomarker for prognosis that could be considered a potential epigenetic and immunotherapeutic target for treatment.
| S-EPMC6803540 | biostudies-literature
Project description:Breast-invasive carcinoma (BRCA) is the most frequent and malignant tumor in females. Ceruloplasmin (CP) is a multifunctional molecule involved in iron metabolism, but its expression profile, prognostic potential and relationship with immune cell infiltration in BRCA are unknown. Ceruloplasmin mRNA and protein expression was significantly decreased in BRCA patients according to the Oncomine, UALCAN, GEPIA and TCGA databases. Ceruloplasmin expression was strongly correlated with various clinicopathological features of BRCA patients. BRCA patients with high ceruloplasmin expression exhibited shorter survival times than those with low ceruloplasmin expression based on the Kaplan-Meier plotter and PrognoScan databases. GO and KEGG analyses and GSEA revealed a strong correlation between ceruloplasmin and various immune-related pathways. Ceruloplasmin expression was significantly associated with the infiltration of immune cells into tumor sites by analyzing the TIMER and CIBERSORT. Additionally, ceruloplasmin was positively correlated with immune checkpoints in BRCA. These findings suggest that low ceruloplasmin expression correlates with a favorable prognosis and tumor immune cell infiltration in BRCA patients. Ceruloplasmin may serve as a therapeutic target and predict the efficacy of immunotherapy for BRCA.
| S-EPMC8436892 | biostudies-literature
Project description:Several diseases have been linked to the dysfunction of anoctamins. Anoctamins play a wide range of physiological roles, including cell proliferation, migration, epithelial secretion, and calcium-activated chloride channel activity. However, the function of anoctamin 10 (ANO10) in breast cancer is still unclear. ANO10 was highly expressed in bone marrow, blood, skin, adipose tissue, thyroid gland and salivary gland, while ANO10 was expressed at low levels in liver and skeletal muscle. Compared to benign breast lesions, the protein level of ANO10 was lower in malignant breast tumors. However, breast cancer patients with low ANO10 expression have favorable survival outcomes. ANO10 was negatively correlated with the infiltration of memory CD4 T cells, naïve B cells, CD8 T cells, chemokines and chemokine receptors. Furthermore, the ANO10 low expression group was more sensitive to certain chemotherapy drugs, including bleomycin, doxorubicin, gemcitabine, mitomycin and etoposide. Altogether, ANO10 is a potential biomarker that can effectively predict the prognosis of breast cancer. Our findings highlight the promising prognostic value and therapeutic target of ANO10 in breast cancer.
| S-EPMC10244099 | biostudies-literature
Project description:Mesothelin (MSLN) is a glycoprotein with various expression degrees in different tumors including mesothelioma, ovarian cancer, pancreatic cancer, etc. MSLN is considered to play an important role in cell survival, proliferation, and tumor progression. Although the expression of MSLN in tumors makes it a potential therapeutic target, its mechanism of action is still unclear, especially its correlation with immune cells infiltration in the tumor microenvironment has not been investigated. In this study, we detected the overexpression of MSLN in ovarian cancer using database analysis and tissue-array staining. We further evaluated the diagnostic value of MSLN and found it was associated with poor overall survival in ovarian cancer. In addition, the high expression of MSLN was significantly related to the immune-related genes and chemoresistant genes. We confirmed the overexpression of MSLN in the chemoresistant ovarian cancer cell lines. Our research suggests that MSLN participates in a variety of pathways related to the suppression of immune activation and promotion of chemoresistance, leading to a poor prognosis in ovarian cancer.
| S-EPMC9174524 | biostudies-literature
Project description:BackgroundThe SNCA gene is a critical gene in Parkinson's disease (PD) pathology. Accumulating evidence indicates that SNCA is involved in tumorigenesis; however, the role of SNCA in lung adenocarcinoma (LUAD) remains unclear. This study aimed to explore the potential value of SNCA as a prognostic and diagnostic molecular marker in LUAD.MethodsIn this study, we explored the expression pattern, prognostic value, and promoter methylation status of SNCA in LUAD based on Oncomine, UALCAN, and Kaplan-Meier Plotter. Then, using TIMER, we investigated the correlation between SNCA expression and immune infiltration. And cBioPortal were used to analysis the correlation between SNCA expression and immune checkpoint. The transcriptome data of A549 cells overexpressing SNCA were used to further study the potential immune role of SNCA in LUAD. The effect of SNCA on proliferation of A549 cells were evaluated by CCK-8, EdU and colony formation. Finally, LUAD cell lines treated with 5-aza-dC were used to explore the correlation between increased promoter methylation and downregulated mRNA expression of SNCA.ResultsIn general, the expression level of SNCA in LUAD tissue was lower than that in normal tissue, and high expression of SNCA was related to better prognosis. There were significant positive correlations between SNCA expression and immune infiltrations, including CD8+ T cells, macrophages, neutrophils, dendritic cells, B cells, and CD4+ T cells, and immune checkpoints, suggesting that immune infiltration was one of the reasons for the influence of SNCA on prognosis in LUAD. The transcriptome data of A549 cells overexpressing SNCA were further used to screen the relevant immune-related genes regulated by SNCA. Enrichment analysis confirmed that SNCA participates in the PI3K-AKT signaling pathway and other key tumor signaling pathways and regulates the expression of MAPK3, SRC, PLCG1, and SHC1. Cellular proliferation assay showed that SNCA could inhabit the growth of A549 cells via inhibiting activity of PI3K/AKT/ mTOR pathway. Finally, analysis of the methylation level of SNCA promoter showed that the promoter methylation negatively correlated with mRNA level. The expression of SNCA in LUAD cell lines was significantly upregulated by treatment with 5-aza-dC.ConclusionHigh methylation of SNCA promoter in LUAD is one of the reasons for the downregulation of SNCA mRNA level. Given that SNCA could inhibit the proliferation of A549 cells and correlates with immune infiltrates, it may serve as a prognostic biomarker in LUAD.
| S-EPMC9009002 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent malignancies and is associated with high mortality. Transmembrane protein 147 (TMEM147) is a seven-transmembrane protein that may mediate immune regulation. However, the relevance of TMEM147 to immune regulation in HCC and the prognosis of HCC patients are unclear.MethodsWe analyzed TMEM147 expression in HCC by using the Wilcoxon rank-sum test. Real time quantitative PCR (RT-qPCR) and Western blot analysis of tumor tissues and cell lines were used to verify TMEM147 expression in HCC. The influence of TMEM147 on HCC prognosis was assessed using Kaplan-Meier analysis, Cox regression analysis, and a prognostic nomogram. The functions of the TMEM147-related differentially expressed genes (DEGs) were identified by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and gene set enrichment analysis (GSEA). In addition, we examined the associations between TMEM147 expression and immune infiltration using single-sample gene set enrichment analysis (ssGSEA) and immunofluorescence staining of HCC tissues.ResultsOur results showed that the expression of TMEM147 was significantly higher in human HCC tissues than in adjacent normal liver tissues, with similar findings in human HCC cell lines. High TMEM147 expression was correlated with T stage, pathological stage, histological grade, race, alpha-fetoprotein level, and vascular invasion in HCC. Moreover, we revealed that high TMEM147 expression was associated with shorter survival times and that TMEM147 could be a risk factor for overall survival, along with T stage, M stage, pathological stage, and tumor status. Mechanistic studies revealed that high TMEM147 expression was linked to the B lymphocyte, antigen response, IL6 signaling pathway, cell cycle, Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling pathway, and myelocytomatosis oncogene (MYC) targets. Correspondingly, TMEM147 expression was positively associated with the infiltration of immune cells, including Th2 cells, follicular helper T cells, macrophages, and NK CD56 bright cells in HCC.ConclusionsTMEM147 might be a biomarker for poor prognosis and is related to immune cell infiltration in HCC.
| S-EPMC10257544 | biostudies-literature