Comprehensive Analysis of SFRP Family Members Prognostic Value and Immune Infiltration in Gastric Cancer.
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ABSTRACT:
SUBMITTER: Liu D
PROVIDER: S-EPMC8228899 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundFibroblast growth factor receptors (FGFRs) modulate numerous cellular processes in tumor cells and tumor microenvironment. However, the effect of FGFRs on tumor prognosis and tumor-infiltrating lymphocytes in gastric cancer (GC) remains controversial.MethodsThe expression of four different types of FGFRs was analyzed via GEPIA, TCGA-STAD, and GTEX databases and our 27 pairs of GC tumor samples and the adjacent normal tissue. Furthermore, the Kaplan-Meier plot and the TCGA database were utilized to assess the association of FGFRs with clinical prognosis. The R software was used to evaluate FGFRs co-expression genes with GO/KEGG Pathway Enrichment Analysis. In vitro and in vivo functional analyses and immunoblotting were performed to verify FGFR4 overexpression consequence. Moreover, the correlation between FGFRs and cancer immune infiltrates was analyzed by TIMER and TCGA databases. And the efficacy of anti-PD-1 mAb treatment was examined in NOG mouse models with overexpressed FGFR1 or FGFR4.ResultsThe expression of FGFRs was considerably elevated in STAD than in the normal gastric tissues and was significantly correlated with poor OS and PFS. ROC curve showed the accuracy of the FGFRs in tumor diagnosis, among which FGFR4 had the highest ROC value. Besides, univariate and multivariate analysis revealed that FGFR4 was an independent prognostic factor for GC patients. According to a GO/KEGG analysis, the FGFRs were implicated in the ERK/MAPK, PI3K-AKT and extracellular matrix (ECM) receptor signaling pathways. In vivo and in vitro studies revealed that overexpression of FGFR4 stimulated GC cell proliferation, invasion, and migration. In addition, FGFR1 expression was positively correlated with infiltrating levels of CD8+ T-cells, CD4+ T-cells, macrophages, and dendritic cells in STAD. In contrast, FGFR4 expression was negatively correlated with tumor-infiltrating lymphocytes. Interestingly, overexpression of FGFR1 in the NOG mouse model improved the immunotherapeutic impact of GC, while overexpression of FGFR4 impaired the effect. When combined with an FGFR4 inhibitor, the anti-tumor effect of anti-PD-1 treatment increased significantly in a GC xenograft mouse model with overexpressed FGFR4.ConclusionsFGFRs has critical function in GC and associated with immune cell infiltration, which might be a potential prognosis biomarker and predictor of response to immunotherapy in GC.
| S-EPMC9487308 | biostudies-literature
Project description:Objective: Colorectal cancer (CRC) is one of the common malignant tumors worldwide. Chromobox (CBX) family proteins are important components of epigenetic regulation complexes and are implicated in the development of multiple cancers by blocking differentiation and promoting proliferation. However, little is known about the function of distinct CBX proteins in colorectal cancer. Methods: Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, GeneMANIA, and TIMER were utilized to analyze differential expression, prognostic value, genetic alteration and immune cell infiltration of CBXs in colorectal cancer patients. Results: The expression levels of CBX1/2/3/4/5 and CBX8 were significantly elevated in CRC tissues, whereas the expression levels of CBX6/7 were reduced. CBX3 was significantly associated with the clinical cancer stage and short disease-free survival (DFS) in CRC patients. High mRNA expression of CBX5/6 was associated with short overall survival (OS) in rectal cancer patients. CBX3/5/6 could be potential prognostic biomarkers for the survival of CRC patients. Moreover, the functions of the differentially expressed CBXs were primarily related to the SUMOylation of DNA methylation proteins and chromatin organization and may regulate the pluripotency of stem cells. The expression of CBXs were significantly correlated with the infiltration of diverse immune cells, including six types of CD4+ T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells in colon cancers and rectal cancers. Conclusions: Our study may provide novel insights for the selection of prognostic biomarkers of CBX family in colorectal cancer.
| S-EPMC7498700 | biostudies-literature
Project description:Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. The insulin-like growth factor-binding protein (IGFBP) family is involved in tumorigenesis and the development of multiple cancers. However, little is known about the prognostic value and regulatory mechanisms of IGFBPs in GBM. Oncomine, Gene Expression Profiling Interactive Analysis, PrognoScan, cBioPortal, LinkedOmics, TIMER, and TISIDB were used to analyze the differential expression, prognostic value, genetic alteration, biological function, and immune cell infiltration of IGFBPs in GBM. We observed that IGFBP1, IGFBP2, IGFBP3, IGFBP4, and IGFBP5 mRNA expression was significantly upregulated in patients with GBM, whereas IGFBP6 was downregulated; this difference in mRNA expression was statistically insignificant. Subsequent investigations showed that IGFBP4 and IGFBP6 mRNA levels were significantly associated with overall survival in patients with GBM. Functional Gene Ontology Annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that genes coexpressed with IGFBP4 and IGFBP6 were mainly enriched in immune-related pathways. These results were validated using the TIMER and TSMIDB databases. This study demonstrated that the IGFBP family has prognostic value in patients with GBM. IGFBP4 and IGFBP6 are two members of the IGFBP family that had the highest prognostic value; thus, they have the potential to serve as survival predictors and immunotherapeutic targets in GBM.
| S-EPMC9273392 | biostudies-literature
Project description:Objective: Ficolin (FCN) family proteins are part of the innate immune system, play a role as recognition molecules in the complement system, and are associated with tumor development. The mechanism of its role in immunotherapy of hepatocellular carcinoma (HCC) is unclear. Methods: In this study, we used the TCGA database, HPA database, Gene Expression Profile Interaction Analysis (GEPIA), Kaplan-Meier plotter, TCGAportal, cBioPortal, GeneMANIA, TIMER, and TISIDB to analyze Ficolin family proteins (FCN1, FCN2 and FCN3, FCNs) in patients with hepatocellular carcinoma for differential expression, prognostic value, genetic alterations, functional enrichment, and immune factor correlation analysis. Results: The expression levels of FCN1/2/3 were significantly reduced in patients with HCC. Among them, FCN3 showed significant correlation with Overall Survival (OS), Progressive Free Survival (PFS) and Relapse Free Survival (RFS) in HCC. FCN1 and FCN3 may be potential prognostic markers for survival in patients with HCC. In addition, the functions of differentially expressed FCNs were mainly related to complement activation, immune response, apoptotic cell clearance and phagocytosis. FCNs were found to be significantly correlated with multiple immune cells and immune factors. Expression of FCN1 and FCN3 differed significantly in the immune and stromal cell component scores of HCC. analysis of the tumor mutation burden (TMB) and microsatellite instability (MSI) of FCNs with pan-cancer showed that FCN3 was significantly correlated with both. Conclusions: Our study provides new insights into the link between the FCN family and immunotherapy for HCC, and FCN3 may serve as a prognostic biomarker for HCC.
| S-EPMC9343789 | biostudies-literature
Project description:BackgroundKindlin Family Members have been reported to be aberrantly expressed in various human cancer types and involved in tumorigenesis, tumor progression, and chemoresistance. However, their roles in non-small cell lung cancer (NSCLC) remain poorly elucidated.MethodsWe analyzed the prognostic value and immune infiltration of Kindlins in NSCLC through Oncomine, GEPIA, UALCAN, CCLE, Kaplan‑Meier plotter, cBioPortal, TIMER, GeneMANIA, STRING, and DAVID database. Additionally, the mRNA expression levels of Kindlins were verified in 30 paired NSCLC tissues and NSCLC cell lines by real-time PCR.ResultsThe expression level of FERMT1 was remarkably increased in NSCLC tissues and NSCLC cell lines, while FERMT2 and FERMT3 were reduced. Kindlins expressions were associated with individual cancer stages and nodal metastasis. We also found that higher expression level of FERMT1 was obviously correlated with worse overall survival (OS) in patients with NSCLC, while higher FERMT2 was strongly associated with better overall survival (OS) and first progression (FP). Additionally, the expression of FERMT2 and FERMT3 were obviously correlated with the immune infiltration of diverse immune cells. Functional enrichment analysis has shown that Kindlins may be significantly correlated with intracellular signal transduction, ATP binding and the PI3K-Akt signaling pathway in NSCLC.ConclusionsThe research provides a new perspective on the distinct roles of Kindlins in NSCLC and likely has important implications for future novel biomarkers and therapeutic targets in NSCLC.
| S-EPMC8091749 | biostudies-literature
Project description:BackgroundSecreted frizzled-related protein (SFRP) is a crucial regulator of Wnt signaling, involved in multiple biological processes including cell proliferation and metastasis. Despite the accumulation of evidence that indicated that SFRPs are differentially expressed and play a key role in various malignancies, the function of different SFRPs in colorectal cancer (CRC) remains insufficiently studied.MethodsMulticenter databases, including GEPIA, cBioPortal, UALCAN, Pathway Commons, STRING, TIMER, CCLE, and LinkedOmics, comprehensively analyzed differential expression, prognostic value, genetic alterations, signaling pathways, immune cell infiltration, and associated genes of the SFRP family in CRC patients. Colony formation, wound healing, and transwell assays were performed to further validate in vitro.ResultsSFRP family members were differentially expressed in CRC, with each member showing varying degrees of genetic alterations. Except for SFRP5, the remaining members show a significant correlation with immune cells. Interestingly, only SFRP2 significantly correlated with CRC prognosis and stage. Additionally, SFRP2 participated in a number of critical biological processes, including metastasis and cell proliferation. Moreover, cell function assays suggested the elimination of SFRP2 inhibits the proliferation, migration, and invasion of HCT116 cells.ConclusionsThe differential expression of SFRP2 is closely associated with the prognosis of CRC patients. In addition, abnormal expression of SFRP2 has a significant impact on the progression of CRC, including proliferation, migration, and invasion. SFRP2 may become a novel prognostic factor for CRC.
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Project description:BackgroundCalpains (CAPNs) are intracellular calcium-activated neutral cysteine proteinases involved in cancer initiation, progression, and metastasis. However, its role in pancreatic cancer (PC) is still unclear. This study aims to identify the prognostic value and immune infiltration of CAPNs for PC patients using comprehensive bioinformatics analyzes.MethodsWe analyzed the transcription levels of CAPNs in different cancers from Oncomine, differential gene expression in tumor/normal tissues and pathological stage through GEPIA database, the prognostic value of the mRNA expression of CAPNs by Kaplan-Meier plotter, the protein expression comparison of different CAPNs in human tumor/normal tissues from The Human Protein Atla, the CAPNs gene alterations through cBioPortal, the prediction of protein-protein interactions by STRING and GeneMANIA, the functional enrichment of discrepant CAPNs by GO and KEGG, and the immune infiltration of CAPNs by ssGSEA.ResultsOur results showed that CAPN1, 2, 4, 5, 6, 8, 9, 10, and 12 were highly expressed in PC. CAPN1, 5, 8, and 12 expression levels were positively correlated with individual cancer stages. Furthermore, CAPN1, 2, 5, and 8 expression levels were negatively correlated with overall survival (OS) and recurrence-free survival (RFS), while CAPN10 was positively correlated with OS and RFS. We found that CAPN1, 2, 5, and 8 were correlated with tumor-infiltrating T follicular helper cells and CAPN10 with tumor-infiltrating T helper 2 cells. Functional enrichment analysis showed that differentially expressed CAPNs (CAPN1, 2, 5, 8, and 10) are involved in axonogenesis, cell-substrate adhesion, immune response-activating cell surface receptor signaling pathway, and cell junction organization in PC.ConclusionsThese results suggested that CAPN1, 2, 5, 8, and 10 could be used as prognostic biomarkers in PC and improve individualized treatment strategies.
| S-EPMC8748070 | biostudies-literature
Project description:BackgroundThe transcription factor Spi-1 proto-oncogene (SPI1, also known as PU.1) is a key regulator of signal communication in the immune system and is essential for the development of myeloid cells and lymphocytes. However, the potential role of SPI1 in gastric cancer (GC) and the correlations between SPI1 and immune infiltration remain unclear.MethodsIn the present study, multiple databases including ONCOMINE, TIMER, Kaplan-Meier Plotter, and The Cancer Genome Atlas were used to explore the expression levels and prognostic value of SPI1 in GC. cBioPortal was used to explore the possible reasons for the increased expression of SPI1 in GC. The correlations between SPI1 expression and tumor-infiltrating immune cells (TICs) were analyzed using CIBERSORT and TIMER. Gene set enrichment analysis was used to determine the biological function of SPI1 in the development of GC. In addition, a risk signature based on SPI1-related immunomodulators was constructed to accurately evaluate the prognosis of patients with GC. The upregulation of SPI1 expression in GC was further confirmed through immunohistochemistry, western blotting, and real-time quantitative PCR (RT-qPCR) assay.ResultsThe expression of SPI1 was increased significantly in GC according to multiple databases, and high expression of SPI1 was related to poor prognosis and progression of GC. The main factor influencing the high expression of SPI1 mRNA in GC may be diploidy, not DNA methylation. Moreover, immunohistochemistry, western blotting, and RT-qPCR assays also confirmed the upregulated expression of SPI1 in GC. CIBERSORT analysis revealed that SPI1 expression was correlated with seven types of TICs (naive B cells, resting memory CD4 T cells, activated memory CD4 T cells, activated natural killer cells, resting natural killer cells, M2 macrophages, and resting dendritic cells). Gene set enrichment analysis indicated that SPI1 might be related to immune activation in GC and participate in cell cycle regulation. In addition, based on SPI1-related immunomodulators, we developed multiple-gene risk prediction signatures and constructed a nomogram that can independently predict the clinical outcome of GC.ConclusionThe results of the present study suggest that SPI1 has a critical role in determining the prognosis of GC patients and may be a potential immunotherapeutic target.
| S-EPMC8882873 | biostudies-literature
Project description:The Schlafen (SLFN) gene family plays an important role in immune cell differentiation and immune regulation. Previous studies have found that the increased SLFN5 expression in patients with intestinal metaplasia correlates with gastric cancer (GC) progression. However, no investigation has been conducted on the SLFN family in GC. Therefore, we systematically explore the expression and prognostic value of SLFN family members in patients with GC, elucidating their possible biological function and its correlation with tumor immune cells infiltration. TCGA database results indicated that the SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN13 expression was significantly higher in GC. The UALCAN and KM plotter databases indicated that enhanced the SLFN family expression was associated with lymph node metastasis, tumor stage, and tumor grade and predicted an adverse prognosis. cBioportal database revealed that the SLFN family had a high frequency of genetic alterations in GC (about 12%), including mutations and amplification. The GeneMANIA and STRING databases identified 20 interacting genes and 16 interacting proteins that act as potential targets of the SLFN family. SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN14 may be implicated in the immunological response, according to Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Additionally, Timer and TISIDB databases indicate that SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN14 are involved in the immune response. Furthermore, Timer, TCGA, and TISIDB databases suggested that the SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN14 expression in GC is highly linked with immune cell infiltration levels, immune checkpoint, and the many immune cell marker sets expression. We isolated three samples of peripheral blood mononuclear cell (PBMC) and activated T cells; the results showed the expression of SLFN family members decreased significantly when T cell active. In conclusion, the SLFN family of proteins may act as a prognostic indicator of GC and is associated with immune cell infiltration and immune checkpoint expression in GC. Additionally, it may be involved in tumor immune evasion by regulating T cell activation.
| S-EPMC9452737 | biostudies-literature
Project description:BackgroundThe SET and MYND domain-containing (SMYD) gene family comprises a set of genes encoding lysine methyltransferases. This study aimed to clarify the relationship between the expression levels of SMYD family members and the prognosis and immune infiltration of malignant tumors of the digestive system.MethodsThe Oncomine, Ualcan, Kaplan-Meier Plotter, cBioPortal, Metascape, and TIMER databases and tools were used to analyze the correlation of SMYD family mRNA expression, clinical stage, TP53 mutation status, prognostic value, gene mutation, and immune infiltration in patients with esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD).ResultsIn ESCA, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/3 with the clinical stage, that of SMYD2/3/4/5 with TP53 mutation status, that of SMYD2/4/5 with overall survival (OS), and that of SMYD1/2/3/4 with relapse-free survival (RFS). In LIHC, the mRNA expression of SMYD1/2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/4/5 with the clinical stage, that of SMYD3/5 with TP53 mutation status, that of SMYD2/3/4/5 with OS, and that of SMYD3/5 with RFS. In STAD, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD1/4 with the clinical stage, that of SMYD1/2/3/5 with TP53 mutation status, that of SMYD1/3/4 with OS, and that of SMYD1/3 with RFS. Furthermore, the function of SMYD family mutation-related genes in ESCA, LIHC, and STAD patients was mainly related to pathways, such as mitochondrial gene expression, mitochondrial matrix, and mitochondrial translation. The expression of SMYD family genes was significantly correlated with the infiltration of six immune cell types and eight types of immune check sites.ConclusionSMYD family genes are differentially expressed and frequently mutated in malignant tumors of the digestive system (ESCA, LIHC, and gastric cancer). They are potential markers for prognostic prediction and have important significance in immunity and targeted therapy.
| S-EPMC8322783 | biostudies-literature