ADORA1 is a diagnostic-related biomarker and correlated with immune infiltrates in papillary thyroid carcinoma.
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ABSTRACT:
SUBMITTER: Lin X
PROVIDER: S-EPMC8176250 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PTP4A3 plays an important role in the tumorigenesis and metastasis of multiple tumors, but its prognostic role in renal cancer is not well understood. We utilized the Oncomine and Tumor Immunoassay Resource databases to examine the differential expression of PTP4A3 in tumor tissues and normal tissues in breast, urinary tract, gastrointestinal tract and skin. Using the GEPIA and PrognoScan databases, the independent prognostic role of PTP4A3 was confirmed in clear cell renal cell cancer and papillary renal cell cancer. Expression of PTP4A3 were obviously higher in tumor tissue compare with normal tissues (P=0.028). We haven't found the associations of PTP4A3 and clinicopathological features in our IHC cohort. Ectopic expression of PTP4A3 promotes proliferation, migration and invasion and increased the mRNA level of TGFB1 in RCC cell lines. Immunohistochemical staining indicated that the expression of PTP4A3 associates with CD3+ (P =0.037)/CD8+ (P =0.037) intratumor TILs, not with invasive margins in renal cancer. Comprehensive analysis of immune infiltration in the TIMER database correlated PTP4A3 expression with the infiltration of B cells, CD8+ T cells, CD4+ T cells and neutrophils in both clear cell renal cell carcinoma and papillary renal cell carcinoma. PTP4A3 expression was associated with the infiltration of dendritic cells in papillary renal cell carcinoma. We further confirmed that the infiltration of B cells and CD8+ T cells was associated with poor prognosis in papillary renal cell carcinoma patients, consistent with the prognostic role of PTP4A3 in papillary renal cell carcinoma. PTP4A3 expression correlated genes involved in B cells, monocytes, M1 macrophages, Th2 and Treg cells in papillary renal cell carcinoma. These results suggest PTP4A3 as a prognostic factor with a role in regulating immune cell infiltration in papillary renal cell carcinoma.
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Project description:Epidermal growth factor receptor 2 (ERBB2) is commonly over-expressed in advanced or metastatic tissues of papillary thyroid cancer (PTC) with poor prognosis, while it remains unknown whether ERBB2 plays a role in the progression of PTC. Thus, we analyzed the data derived from online repositories, including TCGA, KEGG, GO, GeneMANIA, and STRING, to explore the relationship between ERBB2 expression and prognosis, tumor phenotypes of interest, and immune infiltrates in PTC. Compared to normal thyroid tissue, ERBB2 was up-regulated in PTC samples (p < 0.001); In comparison with the group with low expression of ERBB2, the group with high expression of ERBB2 had poorer progression-free interval in stage III/IV patients (p = 0.008) and patients aged >45 years (p = 0.019). The up-regulated ERBB2 was associated with iodine metabolism dysfunction, proliferation, metastasis, angiogenesis, and drug resistance. The expression of ERBB2 negatively correlated with enrichment scores of B cells (r = -0.176, p < 0.001), CD8+ T cells (r = -0.160, p < 0.001), cytotoxic cells (r = -0.219, p < 0.001), NK CD56dim cells (r = -0.218, p < 0.001), plasmacytoid dendritic cells (r = -0.267, p < 0.001), T cells (r = -0.164, p < 0.001), T follicular helper cells (r = -0.111, p = 0.012), gamma delta T cells (r = -0.105, p = 0.017), and regulatory T cells (r = -0.125, p = 0.005). In conclusion, ERBB2 may serve as a prognostic biomarker and an immunotherapeutic target in PTC, deserving further exploration.
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Project description:Kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) are the most common RCC types. RCC has high immune infiltration levels, and immunotherapy is currently one of the most promising treatments for RCC. Collagen triple helix repeat containing 1 (CTHRC1) is an extracellular matrix protein that regulates tumor invasion and modulates the tumor microenvironment. However, the association of CTHRC1 with the prognosis and tumor-infiltrating lymphocytes of KIRP and KIRC has not been reported. We examined the CTHRC1 expression differences in multiple tumor tissues and normal tissues via exploring TIMER, Oncomine, and UALCAN databases. Then, we searched the Kaplan-Meier plotter database to evaluate the correlation of CTHRC1 mRNA level with clinical outcomes. Subsequently, the TIMER platform and TISIDB website were chosen to assess the correlation of CTHRC1 with tumor immune cell infiltration level. We further explored the causes of aberrant CTHRC1 expression in tumorigenesis. We found that CTHRC1 level was significantly elevated in KIRP and KIRC tissues relative to normal tissues. CTHRC1 expression associates with tumor stage, histology, lymph node metastasis, and poor clinical prognosis in KIRP. The CTHRC1 level correlates to tumor grade, stage, nodal metastasis, and worse survival prognosis. Additionally, CTHRC1 is positively related to different tumor-infiltrating immune cells in KIRP and KIRC. Moreover, CTHRC1 was closely correlated with the gene markers of diverse immune cells. Also, high CTHRC1 expression predicted a worse prognosis in KIRP and KIRC based on immune cells. Copy number variations (CNV) and DNA methylation might contribute to the abnormal upregulation of CTHRC1 in KIRP and KIRC. In conclusion, CTHRC1 can serve as a biomarker to predict the prognosis and immune infiltration in KIRP and KIRC.
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Project description:Cyclin dependent kinase inhibitor 2A (CDKN2A) is an essential regulator of immune cell functionality, but the mechanisms whereby it drives immune infiltration in hepatocellular carcinoma (HCC) remain unclear. In the present study, we studied the association with CDKN2A expression and immune invasion with the risk of developing HCC. A totally of 2207 different genes were found between HCC and adjacent liver tissues from TCGA and GEO databases. CDKN2A was highly expressed in HCC and associated with poorer overall survival and disease-free survival. Notably, CDKN2A expression was positively correlated with infiltrating levels into purity, B cell, CD+8 T cell, CD+4 T cell, macrophage, neutrophil, and dendritic cells in HCC. CDKN2A expression showed strong correlations between diverse immune marker sets in HCC. These findings suggest that CDKN2A expression potentially contributes to regulation of tumor-associated macrophages and can be used as a prognostic biomarker for determining prognosis and immune infiltration in HCC.
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Project description:Background: KLHL5 (Kelch Like Family Member 5) is differentially expressed in gastric cancer, but its correlation with prognosis and functioning mechanism in gastric cancer remain unclear. Methods: The Oncomine database and TIMER were employed to appraise the KLHL5 expression in a variety of cancers. The correlation between KLHL5 expression and patient prognosis was extracted from the Kaplan-Meier plotter, GEPIA, and PrognoScan database. Then the relationship between KLHL5 expression and inflammatory infiltrate profiles was inquired by TIMER. Finally, GEPIA and TIMER were explored for the correlative significance between KLHL5 expression and immune cell-related marker sets. Results: KLHL5 was found to be differentially expressed and correlated with clinical outcomes in several types of cancers in the TCGA database. Especially, KLHL5 mRNA expression was upregulated and correlated with poorer overall survival and progression-free survival in gastric cancer. Moreover, elevated KLHL5 expression was significantly related with patient node stage, infiltration level, and expression of multiple immune marker sets. Conclusions: These results implicate that KLHL5 expression is closely linked with patient clinical outcomes and the microenvironmental infiltration level in different neoplasms. This indicates that KLHL5 is a modulator in infiltrate recruitment, shaping the landscape of immune cell infiltration. Thus, it represents an eligible prognostic predictor for gastric malignancy.
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Project description:BackgroundMammalian STE20-like kinase 1 (MST1/STK4/KRS2) is a highly conserved serine/threonine kinase and a central member of the Hippo signaling pathway. STK4 has been reported to play important roles in various tumors, but a systematic and comprehensive study of its function in clear cell renal cell carcinoma (ccRCC) has not been conducted.MethodsIn this study, we used immunohistochemistry (IHC), western blot (WB), quantitative real-time PCR (qPCR) experiments, and bioinformatics analysis to comprehensively analyze the expression, prognostic value, and immune infiltration of STK4 in ccRCC.ResultsAnalysis of the TCGA database showed that the expression level of the STK4 gene in ccRCC patients depended on tumor stage, grade, and distant lymphatic metastasis. This was further confirmed by the results of IHC, WB, and qPCR. In addition, we used the receiver operating characteristic curve (ROC curve) to elucidate the diagnostic value of STK4 in ccRCC patients. According to the findings of the TIMER database, the high expression of STK4 is significantly associated with the survival of kidney cancer (including ccRCC) patients (p < 0.001), suggesting that STK4 is a reliable prognostic predictor. We then used gene set enrichment analysis (GSEA) to explore the mechanisms behind STK4 function in ccRCC. We found that STK4 may play a role in immune regulation interactions. Subsequently, we performed immune infiltration analysis of STK4. The results showed that STK4 may regulate the development of ccRCC by affecting the immune infiltration of NK and pDC cells.ConclusionsSTK4 may be a prognostic marker for ccRCC and may help identify new strategies for treating ccRCC patients.
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Project description:BackgroundImmune response is prevalently related with major depressive disorder (MDD) pathophysiology. However, the study on the relationship between immune-related genes (IRGs) and immune infiltrates of MDD remains scarce.MethodsWe extracted expression data of 148 MDD patients from 2 cohorts, and systematically characterized differentially expressed IRGs by using limma package in R software. Then, the LASSO and multivariate logistic regression analysis was used to identify the most powerful IRGs. Next, we analyzed the relationship between IRGs and immune infiltrates of MDD. Finally, GSE76826 was used to to verificate of IRGs as a diagnostic markers in MDD.Results203 different IRGs s in MDD has been identified (P < 0.05). GSEA revealed that the different IRGs was more likely to be enriched in immune-specific pathways. Then, a 9 IRGs was successfully established to predict MDD based on LASSO. Next, 4 IRGs was obtained by multivariate logistic regression analysis, and AUC for CD1C, SPP1, CD3D, CAMKK2, and IRGs model was 0.733, 0.767, 0.816, 0.800, and 0.861, suggesting that they have a good diagnostic performance. Furthermore, the proportion of T cells CD8, T cells γδ, macrophages M0, and NK cells resting in MDD group was lower than that in the healthy controls, suggesting that the immune system in MDD group is impaired. Simultaneously, CD3D was validated a reliable marker in MDD, and was positively correlated with T cells CD8. GSEA revealed high expression CD3D was more likely to be enriched in immune-specific pathways, and low expression CD3D was more likely to be enriched in glucose metabolism metabolism-specific pathways.ConclusionsWe applied bioinformatics approaches to suggest that a 4 IRGs could serve as diagnostic markers to provide a novel direction to explore the pathogenesis of MDD.
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Project description:PurposeThe serine protease inhibitor clade E member 1 (SERPINE1) has been studied as a potential biomarker in a variety of cancers, but poorly studied in gastric cancer (GC). The purpose of this study was to explore the prognostic value of SERPINE1 in GC and primarily analyze its functions.MethodsWe analyzed the the prognostic value of SERPINE1 and studied the relationship with clinicopathologic biomarkers in gastric cancer. The expression of SERPINE1 was analyzed by GEO and TCGA databases. Moreover, we validated the results by immunohistochemistry. Next, the correlation analysis between SERPINE1 and the cuproptosis-related genes was analyzed by the "Spearman" method. CIBERSORT and TIMER algorithms were used to analyze the correlation of SERPINE1 with immune infiltration. Furthermore, GO and KEGG gene enrichment analyses were used to study the functions and pathways that SERPINE1 might be involved in. Then, drug sensitivity analysis was performed using CellMiner database. Finally, a cuproptosis-immune-related prognostic model was constructed using genes related to immune and cuproptosis, and verified against external datasets.ResultsSERPINE1 was up-regulated in gastric cancer tissues, which tends toward poor prognosis. Using immunohistochemistry experiment, the expression and prognostic value of SERPINE1 were verified. Then, we found that SERPINE1 was negatively correlated with cuproptosis-related genes FDX1, LIAS, LIPT1, and PDHA1. On the contrary, SERPINE1 was positively correlated with APOE. This indicates the effect of SERPINE1 on the cuproptosis process. Furthermore, by conducting immune-related analyses, it was revealed that SERPINE1 may promote the inhibitory immune microenvironment. The infiltration level of resting NK cells, neutrophils, activated mast cells, and macrophages M2 was positively correlated with SERPINE1. However, B cell memory and plasma cells were negatively correlated with SERPINE1. Functional analysis showed that SERPINE1 was closely related to angiogenesis, apoptosis, and ECM degradation. The KEGG pathway analysis showed that SERPINE1 may be associated with P53, Pi3k/Akt, TGF-β, and other signaling pathways. Drug sensitivity analysis showed that SERPINE1 could be also seen as a potential treatment target. The risk model based on SERPINE1 co-expression genes could better predict the survival of GC patients than SERPINE1 alone. We also verified the prognostic value of the risk score by GEO external datasets.ConclusionSERPINE1 is highly expressed in gastric cancer and related to poor prognosis. SERPINE1 may regulate cuproptosis and the immune microenvironment by a series of pathways. Therefore, SERPINE1 as a prognostic biomarker and potential therapeutic target deserves further study.
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Project description:Transmembrane protease serine 4 (TMPRSS4) is a cancer-associated protease associated with prognosis in various types of cancer. Mechanistically, TMPRSS4 mainly regulates malignant phenotypes, such as tumor invasion and metastasis, by either the epithelial to mesenchymal transition (EMT) program or promoting the proliferation of cancer cells. To date, TMPRSS4 and immune infiltration in thyroid carcinoma (TC) are largely unknown. Thus, this paper evaluated the expression of TMPRSS4 in tumor tissue through the Tumor Immune Estimation Resource (TIMER) database, and Oncomine, and its correlation with clinical parameters by UALCAN databases. Furthermore, we analyzed its prognostic value from Kaplan-Meier Plotter database, and the relationship between TMPRSS4 and the abundance of tumor-infiltrating lymphocytes (TILs) in TC in TISIDB, screening potential immune targets to explore novel mechanisms for the clinical management of TC. Finally, we assessed the correlation between TMPRSS4 and some immune markers to uncover a potential immune-related biomarker in TC patients by TIMER2.0. The results revealed that TMPRSS4 was highly expressed in TC and was also associated with lymphatic metastasis, advanced stage, histological subtype, and favorable clinical outcome. The stratified analysis based on immune cell content showed that decreased TMPRSS4 had worse prognosis in CD8+ T cell-enriched TC patients. TMPRSS4 was positively correlated with tumor immune infiltration and the expression of gene markers of immune cells. Notably, its expression was lower in the lymphocyte-depleted subtype than in other immunosubtypes in TC. Moreover, TMPRSS4 was closely related to chemokines as well as their receptors and the immunosuppressive checkpoints CTLA-4, PD-1, and HLA-G. In conclusion, TMPRSS4 may act as a novel biomarker predicting prognosis and immune infiltration in TC.
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Project description:BackgroundAutophagy plays a vital role in the progression of the tumor. We aimed to investigate the expression, prognostic value, and immune infiltration of autophagy-related genes in oral carcinoma via bioinformatics analysis.MethodsThe microarray datasets (GSE146483 and GSE23558) of oral carcinoma were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between normal and diseased groups were identified by the Limma package. The screened autophagy-related gene was further validated by the human protein atlas (HPA) database, TCGA database, and GSE78060 dataset.ResultsA total of 18 upregulated (top 10: EGFR, TNF, FADD, AURKA, E2F1, CHEK1, BRCA1, BIRC5, EIF2AK2, and CSF2) and 31 downregulated (top 10: MAP1LC3A, PARK2, AGT, IGF1, TP53INP1, CXCL12, IKBKB, SESN1, ULK2, and RRAGD) autophagy-related (DEGs) were identified, and FADD was found to be related to the prognosis of oral cancer patients. Gene set enrichment analysis indicated that FADD-associated genes were significantly enriched in immune-related pathways. Moreover, correlation analysis revealed that FADD expression was associated with immune infiltrates. Upregulation of FADD is associated with poor survival and immune infiltrates in oral cancer.ConclusionWe speculated that FADD is involved in the immune regulation of oral cancer, as well as autophagy.
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