Comprehensive analysis of PPPCs family reveals the clinical significance of PPP1CA and PPP4C in breast cancer.
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ABSTRACT:
SUBMITTER: Xie W
PROVIDER: S-EPMC8805822 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe FAM83 family plays a key role in tumorigenesis and cancer progression. However, the role of the FAM83 family in the development of breast tumors is unclear to date. This report explores the expression, prognostic significance, and function of the FAM83 family members in breast cancer using public databases.MethodsUALCAN database was used to explore the expression of FAM83 family members in breast cancer. Furthermore, we validated the expression of FAM83 family members in twenty pairs of breast cancer and normal tissues by RT-PCR. Kaplan-Meier plotter database was used to explore the prognostic significance of FAM83 family members in breast cancer. GeneMANIA and DAVID databases were used for functional and pathway enrichment analysis of genes co-expressed with FAM83A, FAM83D, FAM83F, and FAM83G. MEXPRESS and UALCAN databases were used to analyze the level of DNA promoter methylation of FAM83A, FAM83D, FAM83F, and FAM83G in breast cancer. TIMER database was utilized to explore the relationships between immune cell infiltration and FAM83A, FAM83D, FAM83F, and FAM83G expression.ResultsAmong FAM83 family members, FAM83A, FAM83D, FAM83F, and FAM83G were higher expressed in breast cancer than in normal tissues. We also validated the significant high expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA in breast cancer than in normal samples. Their increased expression has an adverse prognostic effect on breast cancer patients. These genes co-expressed with FAM83A, FAM83D, FAM83F, and FAM83G might take part in cell proliferation, G2/M transition of the mitotic cell cycle, regulation of apoptosis process and other cancer-related biological processes. In addition, they were mainly enriched in the Hippo signaling pathway, Hedgehog signaling pathway, PI3K/AKT signaling pathway, and other cancer-related pathways. We also found that promoter DNA methylation might regulate the expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA in most CpG islands. At last, we found the expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA was significantly related to immune cell infiltration.ConclusionsFAM83A, FAM83D, FAM83F, and FAM83G were highly expressed in breast cancer tissues and had an adverse effect on the survival outcomes of breast cancer patients. Also, they were involved in breast cancer-related signal pathways. Therefore, they might serve as potential therapeutic targets for breast cancer clinical treatment.
| S-EPMC9158143 | biostudies-literature
Project description:ObjectiveWe aimed to investigate the expression, diagnostic and prognostic values, and potential molecular mechanisms of the origin recognition complex (ORC) in breast cancer (BC).MethodsKaplan-Meier estimation was used to assess the prognostic value of ORC genes, and Oncomine, TCGA, GEO and ULCAN databases were used to analyze their expression in BC. Wilcoxon rank-sum tests were used to evaluate the relationship between ORC gene expression levels and BC clinicopathological features. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of ORC genes in BC. Survival analysis was performed using Kaplan-Meier estimation and Cox regression. A nomogram was constructed to predict 1-, 3-, and 5-year survival probabilities in BC. Gene set enrichment analysis (GSEA) and immune infiltration were used to investigate potential molecular mechanisms of the ORC.ResultsORC1L and ORC6L were highly expressed in BC compared with healthy tissue, while ORC5L expression patterns were inconsistent; no significant differences in ORC2L, ORC3L or ORC4L expression were observed between BC and healthy tissues. ORC1L and ORC6L expression levels were significantly correlated with age, tumor (T) stage and molecular subtype; ORC5L expression was significantly correlated with age and number of nearby lymph nodes with cancer (N stage). ORC6L expression had the highest diagnostic value in BC and was an independent prognostic factor for poor overall survival (OS). ORC6L may be involved in cell cycle progression and may regulate cancer signaling pathways, including NF-κB, P53, and WNT, in BC. ORC6L expression was also associated with immune infiltration.ConclusionORC1L and ORC6L are highly expressed in BC; ORC6L has a high diagnostic value and is an independent prognostic factor for poor OS. ORC6L may be involved in the initiation and progression of BC by regulating cell cycle progression, promoting cancer signaling pathway activation, and influencing tumor immune cell infiltration.
| S-EPMC8684402 | biostudies-literature
Project description:While the molecular functions of miR-200 family have been deeply investigated, a role for these miRNAs as breast cancer biomarkers remains largely unexplored. In the attempt to clarify this, we profiled the miR-200 family members expression in a large cohort of breast cancer cases with a long follow-up (H-CSS cohort) and in TCGA-BRCA cohort. Overall, miR-200 family was found upregulated in breast tumors with respect to normal breast tissues while downregulated in more aggressive breast cancer molecular subtypes (i.e. Luminal B, HER2 and triple negative), consistently with their function as repressors of the epithelial-to-mesenchymal transition (EMT). In particular miR-141-3p was found differentially expressed in breast cancer molecular subtypes in both H-CSS and TCGA-BRCA cohorts, and the combined analysis of all miR-200 family members demonstrated a slight predictive accuracy on H-CSS cancer specific survival at 12 years (survival c-statistic: 0.646; 95%CI 0.538-0.754).
| S-EPMC7859396 | biostudies-literature
Project description:BackgroundThe tumorigenesis of prostate cancer involves genetic mutations. Tumour mutational burden (TMB) is an emerging biomarker for predicting the efficacy of immunotherapy.ResultsSingle-nucleotide polymorphisms were the most common variant type, and C>T transversion was the most commonly presented type of single-nucleotide variant. The high-TMB group had lower overall survival (OS) than the low-TMB group. TMB was associated with age, T stage and N stage. Functional enrichment analysis of differentially expressed genes (DEGs) showed that they are involved in pathways related to the terms spindle, chromosomal region, nuclear division, chromosome segregation, cell cycle, oocyte meiosis and other terms associated with DNA mutation and cell proliferation. Six hub genes, PLK1, KIF2C, MELK, EXO1, CEP55 and CDK1, were identified. All the genes were associated with disease-free survival, and CEP55 and CDK1 were associated with OS.ConclusionsThe present study provides a comprehensive analysis of the significance of TMB and DEGs and infiltrating immune cells related to TMB, which provides helpful information for exploring the significance of TMB in prostate cancer.
| S-EPMC7905899 | biostudies-literature
Project description:BackgroundLarge numbers of studies have identified that procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family members play important roles in tumorigenesis and tumor progression in various cancers. However, the expression pattern, clinical value and function of PLOD family have yet to be analyzed systematically and comprehensively in bladder urothelial carcinoma (BLCA).MethodsWe investigated the transcriptional levels, genetic alteration, biological function, immune cell infiltration, data on survival of PLODs in patients with BLCA based on UALCAN, the Cancer Genome Atlas (TCGA) database, Gene Expression Profiling Interactive Analysis (GEPIA), TIMER, STRING, cBioPortal and GSCALite databases. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed in R software using the Cluster Profiler Bioconductor package. Protein-protein interaction (PPI) network was established by STRING and visualized by using R version (3.6.3) software. Survival analysis was performed using the packages "survminer".ResultsThe mRNA and protein expression patterns of PLOD family members were noticeably increased in BLC compared with normal tissue. The mRNA expression levels of PLOD1-2 genes were significantly correlated with histological subtypes and PLOD1 was significantly correlated with pathological stage. Furthermore, the high expression levels of PLOD1-2 were remarkably associated with poor overall survival (OS) in BLCA patients, meanwhile high expression levels of PLOD1 and PLOD3 were markedly associated with poor progression-free interval (PFI). In co-expression gene analysis, 50 genes were primarily associated with the differentially expressed PLODs in BLCA. Functional enrichment analysis revealed that protein hydroxylation, collagen fibril organization, and lysine degradation were key biological functions of PLODs in BLCA. Moreover, PLOD family genes were identified as being associated with the activities of tumor-infiltrating immune cells and closely associated with immune responses in BLCA.ConclusionPLOD family members might serve as potential therapeutic targets and prognostic markers for BLCA patients' survival.
| S-EPMC9975538 | biostudies-literature
Project description:BackgroundBreast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated.MethodsIn this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan-Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan-Meier Plotter databases. FBXO1 siRNAs were transfected into MCF-7 and MDA-MB-231 cell lines. Expression of FBXO1 in BC cell lines was detected by western-blot and RT-qPCR. Cell proliferation was detected by using CCK-8 kit and colony formation assay. Cell migration was detected by wound-healing and transwell migration assay.ResultsWe found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, knockdown of FBXO1 in MCF7 and MDA-MB-231 cell lines resulted in decreased cell proliferation and migration in vitro. We identified that FBXO1 was an excellent molecular biomarker and therapeutic target for different molecular typing of BC.ConclusionThis study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with different molecular typing of BC. In addition, the overexpression of FBXO1 is always found in breast cancer and predicts disadvantageous prognosis, implicating it could as an appealing therapeutic target for breast cancer patients.
| S-EPMC7903729 | biostudies-literature
Project description:BackgroundAn increasing amount of research over recent years on the anti-metastasis function of the non-metastatic (NME) gene family has been challenged, with some studies identifying its involvement in the promotion of oncogenesis. Therefore, the specific functions of the NME gene family require redefining through a comprehensive analysis of tumor heterogeneity and survival benefit. However, the functions of NME genes have not been comprehensively investigated in breast cancer (BC).MethodsIn this study, ONCOMINE, GEPIA, Kaplan-Meier plotter, cBioPortal, String, and metascape databases were utilized for comparison of the mRNA expression, patient survival and network analysis of NME-associated signaling pathways in BC patients.ResultsThe mRNA expression of NME1 and NME2 was significantly increased in BC. Additionally, high NME 1 and NME2 levels were related to poor overall survival (OS), while the upregulated expression of NME3, NME5, and NME7 indicated prolonged survival. Moreover, increased mRNA level, amplification, or deep deletions in the NME gene family were identified in approximately 41% (450/1098) of all included BC specimens. NME1 and NME2 genes displayed the highest correlation with genetic correlations of the human NME genes in BC. The following pathways were regulated by NME gene upregulation: R-HAS-380270: Recruitment of mitotic centrosome and complexes; GO:0006228: UTP biosynthetic process; R-HAS-380259: Loss of NlP from mitotic centrosomes; hsa03410: Base excision repair; and CORUM:3714: Pericenrin-GCP complex, which was significantly modulated by changes influencing the NME genes.ConclusionsCollectively, our findings revealed that the elevated expression of NME1 and NME2 could act as a biomarker and predictive tool for BC patients with poor prognosis. Furthermore, our findings indicated that NME3, NME5, and NME7 might play the roles of tumor suppressor genes, which require validation through further experiments.
| S-EPMC8798044 | biostudies-literature
Project description:BackgroundTriple-negative breast cancer (TNBC) is a heterogeneous disease with a worse prognosis. However, current therapies have rarely improved the outcome of patients with TNBC. Here we sought to identify novel biomarkers or targets for TNBC.Materials and methodsPatients GSE76275 clinic traits and their corresponding mRNA profiles for 198 TNBC and 67 non-TNBC were obtained from the GEO database. Weighted gene co-expression network analysis (WGCNA) of the GSE76275 keyed out hub genes, and the differentially expressed genes (DEGs) were identified with the cut-off of adjusted P (adj. P) <0.01 and |log2 fold-change (FC)| > 1.5. The hub - DEGs overlapping genes, as key genes, were considered for further study using Kaplan-Meier plotter online analysis. Subsequently, Breast Cancer Gene-Expression Miner v4.0 and tissue microarray analysis were applied to determine the transcriptional and translational levels of every key gene. Following plasmid transfection for overexpression, the proliferation of TNBC cells was determined by CCK8 and colony formation assay. Moreover, xenograft tumor models were canvassed to investigate their effect upon in vivo tumor growth.ResultsFour genes (SIDT1, ANKRD30A, GPR160, and CA12) were found to be associated with relapse-free survival (RFS) in TNBC through WGCNA and DEGs integrated analysis. Patients with a higher level of SIDT1 had significantly better RFS compared to those with lower levels. The transcriptional and translational levels of SIDT1 were validated as downregulated in patients with triple-negative status, negative estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Furthermore, SIDT1 inhibited proliferation of breast cancer cells (MDA-MB-231 and MDA-MB-468) and xenograft studies demonstrated that SIDT1 can suppress tumor growth in vivo.ConclusionThis study suggests that SIDT1 may play a crucial role in TNBC progression and has the potential as a prognostic biomarker of TNBC.
| S-EPMC6792947 | biostudies-literature
Project description:BackgroundBreast cancer (BC) is the most common malignancy in females and remains a main cause of cancer-associated death worldwide. The solute carrier (SLC) groups of membrane transport proteins, which control the influx of zinc, participate in ranging of physiological processes and may provide novel therapeutic targets of cancers. However, the prognostic values of individual SLC family 39 (SLC39A) genes in patients with BC are not clarified.Materials and methodsThe mRNA expression of SLC family 39 genes in BC was evaluated by using the UALCAN database. The prognostic values of overall survival (OS) of SLC family 39 genes in patients with BC were investigated by Kaplan-Meier plotter. The survival analysis of cells was determined by Project Achilles.ResultsThe analytic results suggested that SLC39A1, SLC39A3, SLC39A4, SLC39A5, SLC39A6, SLC39A7, SLC39A9, SLC39A10, SLC39A11 and SLC39A13 were significantly up-regulated in BC tissues compared with normal breast tissues. However, SLC39A8 and SLC39A14 were expressed higher in normal tissues than in BC tissues. High expression of SLC39A2, SLC39A3, SLC39A4, SLC39A5, SLC39A7, SLC39A12 and SLC39A13 was significantly associated with worse OS in patients with BC. In contrast, high mRNA levels of SLC39A6 and SLC39A14 indicated favorable OS. Through subgroup analysis, all abnormal expressed SLC family members were correlated with prognoses of patients with specific BC. Moreover, SLC39A7 was associated with proliferation and cloning of BC.ConclusionsOur results suggested that SLC family 39 members were promising prognostic biomarkers of BC. The SLC39A7 played a key role in growth and survival of BC cells.
| S-EPMC7426635 | biostudies-literature
Project description:G-protein signaling modulators (GPSMs) are a class of proteins involved in the regulation of G protein-coupled receptors, the most abundant family of cell-surface receptors that are crucial in the development of various tumors, including breast cancer. This study aims to identify the potential therapeutic and prognostic roles of GPSMs in breast cancer. Oncomine and UALCAN databases were queried to determine GPSM expression levels in breast cancer tissues compared to normal samples. Survival analysis was conducted to reveal the prognostic significance of GPSMs in individuals with breast cancer. Functional enrichment analysis was performed using cBioPortal and MetaCore platforms. Finally, the association between GPSMs and immune infiltration cells in breast cancer was identified using the TIMER server. The experimental results then showed that all GPSM family members were significantly differentially expressed in breast cancer according to Oncomine and UALCAN data. Their expression levels were also associated with advanced tumor stages, and GPSM2 was found to be related to worse distant metastasis-free survival in patients with breast cancer. Functional enrichment analysis indicated that GPSMs were largely involved in cell division and cell cycle pathways. Finally, GPSM3 expression was correlated with the infiltration of several immune cells. Members of the GPSM class were differentially expressed in breast cancer. In conclusion, expression of GPSM2 was linked with worse distant metastasis-free outcomes, and hence could potentially serve as a prognostic biomarker. Furthermore, GPSM3 has potential to be a possible target for immunotherapy for breast cancer.
| S-EPMC8471503 | biostudies-literature