Screening of differential expressed genes from gene chip and sequencing data and evaluate its prognostic values in males with digestive system neoplasms
Ontology highlight
ABSTRACT: Background
Digestive system neoplasm is a common cancer in males worldwide. This study aimed to explore the commonalities in males with digestive system neoplasms (MDSN) and its clinical relevance. Methods
A total of 46 differential expressed genes (DEGs) in MDSN were identified shared in TCGA and GEO databases. Results
These DEGs significantly affected a variety of cell function and signaling pathways. Of which, a hub of 7 genes (CCNB1, MAD2L1, BUB1, CHEK1, MCM2, CCNA2 and CDC25B) were interacted with each other in protein level and significantly enriched in cell cycle pathway. Further methylation analysis, we found that BUB1, MAD2L1 and MCM2 were hypomethylation via m6A modification. Besides, BUB1, MAD2L1 and MCM2 were co-expressed in mRNA level and up-regulation of them led to worse prognostic in hepatocellular carcinoma, while caused a better prognostic in stomach adenocarcinoma (STAD), and had a race difference between white and Asian people in STAD. Medicine molecules, I-threonine (ID: PA451673) and enzymes (ID: PA164712734) might be efficient medicines in BUB1, MAD2L1 and MCM2 up-regulated MDSN patients. Conclusions
Taken together, hypomethylation via m6A modification might cause BUB1, MAD2L1 and MCM2 up-regulation in MDSN. Dysregulation of BUB1, MAD2L1 and MCM2 function as contrast prognostic in liver hepatocellular carcinoma and STAD. Our study provides more accurate therapeutic targets and prognostic biomarkers for specific cancer types.
SUBMITTER: Fang K
PROVIDER: S-EPMC8797597 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Metastasis associated in colon cancer 1 (MACC1), a newly identified oncogene, has been associated with poor survival of cancer patients by multiple studies. However, the prognostic value of MACC1 in digestive system neoplasms needs systematic evidence to verify. Therefore, we aimed to provide further evidence on this topic by systematic review and meta-analysis. Literature search was conducted in multiple databases and eligible studies analyzing survival data and MACC1 expression were included for meta-analysis. Hazard ratio (HR) for clinical outcome was chosen as an effect measure of interest. According to our inclusion criteria, 18 studies with a total of 2,948 patients were identified. Pooled HRs indicated that high MACC1 expression significantly correlates with poorer OS in patients with digestive system neoplasms (HR = 1.94; 95% CI: 1.49-2.53) as well as poorer relapse-free survival (HR = 1.94, 95% CI: 1.33-2.82). The results of subgroup studies categorized by methodology, anatomic structure, and cancer subtype for pooled OS were all consistent with the overall pooled HR for OS as well. No publication bias was detected according to test of funnel plot asymmetry and Egger's test. In conclusion, high MACC1 expression may serve as a prognostic biomarker to guide individualized management in clinical practice for digestive system neoplasms.
| S-EPMC4452247 | biostudies-literature
Project description:BackgroundThe objective of this study was to develop and validate a nomogram to predict 1-year overall survival (OS) and 2-year OS in patients with high-grade digestive neuroendocrine neoplasms (NENs) as well as to guide selection of subgroups that could benefit from systemic chemotherapy.Subjects, materials, and methodsWe performed a retrospective analysis of 223 patients with NENs of the gut and hepato-biliary-pancreatic system from four centers included in the development cohort. The nomogram was externally validated in a cohort of 90 patients from another one.ResultsThe final model included lactate dehydrogenase, performance status, stage, Ki67, and site of primary tumor, all of which had a significant effect on OS. The uncorrected C-index was 0.761 for OS, and the bias-corrected C-index was 0.744. Predictions correlated well with observed 1-year and 2-year outcomes (judged by eye). The area under the time-dependent receiver operating characteristic curve at 12 months and 24 months was 0.876 and 0.838, respectively. The nomogram performed well in terms of both discrimination and calibration when applied to the validation cohort, and OS was significantly different between the two groups classified by nomogram score (log-rank p < .001).ConclusionThe validated nomogram provided useful prediction of OS, which can be offered for clinicians to improve their abilities to assess patient prognosis, to create clinical risk groups for informing treatment or for patient stratification by disease severity in clinical trials.Implications for practiceThe high-grade neuroendocrine neoplasms of the digestive system are rare malignancies with great heterogeneity. An overall survival nomogram was developed and externally validated in this study. Two subgroups were classified by the nomogram score, and platinum-based chemotherapy may not bring clinical benefit for the low-risk patients.
| S-EPMC7160419 | biostudies-literature
Project description:PD-L1 has been reported to be expressed in diverse human malignancies. However, the prognostic value of PD-L1 in digestive system cancers remains inconclusive. Therefore, we conducted this meta-analysis to evaluate the prognostic impact of PD-L1 expression in digestive system cancers.We searched the PubMed, Embase, and the Chinese National Knowledge Infrastructure for publications concerning PD-L1 expression in digestive system cancers. Correlations of PD-L1 expression level with overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were analyzed.Finally, 32 studies with 7,308 patients were included. Our results show that PD-L1 expression was significantly associated with poorer OS (hazard ratio [HR] =1.44, 95% confidence interval [CI] =1.18-1.76, P<0.001), but not DFS (HR =0.91, 95% CI =0.61-1.37, P=0.657) or RFS (HR =1.27, 95% CI =0.75-2.14, P=0.368). Moreover, in the subgroup analysis, significant associations between PD-L1 expression and OS were found in Asians (HR =1.50, 95% CI =1.19-1.89, P=0.001), gastric cancer (HR =1.43, 95% CI =1.05-1.94, P=0.021), and pancreatic carcinoma (HR =2.64, 95% CI =1.78-3.93, P<0.001).These results suggest that the expression of PD-L1 is associated with worse OS in digestive system cancers, especially in gastric cancer and pancreatic cancer. In addition, PD-L1 may act as a new parameter for predicting poor prognosis and a promising target for anticancer therapy in digestive system cancers.
| S-EPMC5533487 | biostudies-other
Project description:ObjectiveThere is a heated debate on whether the prognostic value of NME1 is favorable or unfavorable. Thus, we carried out a meta-analysis to evaluate the relationship between NME1 expression and the prognosis of patients with digestive system neoplasms.MethodsWe searched PubMed, EMBASE and Web of Science for relevant articles. The pooled odd ratios (ORs) and corresponding 95%CI were calculated to evaluate the prognostic value of NME1 expression in patients with digestive system neoplasms, and the association between NME1 expression and clinicopathological factors. We also performed subgroup analyses to find out the source of heterogeneity.Results2904 patients were pooled from 28 available studies in total. Neither the incorporative OR combined by 17 studies with overall survival (OR = 0.65, 95%CI:0.41-1.03, P = 0.07) nor the pooled OR with disease-free survival (OR = 0.75, 95%CI:0.17-3.36, P = 0.71) in statistics showed any significance. Although we couldn't find any significance in TNM stage (OR = 0.78, 95%CI:0.44-1.36, P = 0.38), elevated NME1 expression was related to well tumor differentiation (OR = 0.59, 95%CI:0.47-0.73, P<0.00001), negative N status (OR = 0.54, 95%CI:0.36-0.82, P = 0.003) and Dukes' stage (OR = 0.43, 95%CI:0.24-0.77, P = 0.004). And in the subgroup analyses, we only find the "years" which might be the source of heterogeneity of overall survival in gastric cancer.ConclusionsThe results showed that statistically significant association was found between NME1 expression and the tumor differentiation, N status and Dukes' stage of patients with digestive system cancers, while no significance was found in overall survival, disease-free survival and TNM stage. More and further researches should be conducted to reveal the prognostic value of NME1.
| S-EPMC4982620 | biostudies-literature
Project description:Introduction: Abnormal status of gene expression plays an important role in tumorigenesis, progression and metastasis of breast cancer. Mechanisms of gene silence or activation were varied. Methylation of genes may contribute to alteration of gene expression. This study aimed to identify differentially expressed hub genes which may be regulated by DNA methylation and evaluate their prognostic value in breast cancer by bioinformatic analysis. Methods: GEO2R was used to obtain expression microarray data from GSE54002, GSE65194 and methylation microarray data from GSE20713, GSE32393. Differentially expressed-aberrantly methylated genes were identified by FunRich. Biological function and pathway enrichment analysis were conducted by DAVID. PPI network was constructed by STRING and hub genes was sorted by Cytoscape. Expression and DNA methylation of hub genes was validated by UALCAN and MethHC. Clinical outcome analysis of hub genes was performed by Kaplan Meier-plotter database for breast cancer. IHC was performed to analyze protein levels of EXO1 and Kaplan-Meier was used for survival analysis. Results: 677 upregulated-hypomethylated and 361 downregulated-hypermethylated genes were obtained from GSE54002, GSE65194, GSE20713 and GSE32393 by GEO2R and FunRich. The most significant biological process, cellular component, molecular function enriched and pathway for upregulated-hypomethylated genes were viral process, cytoplasm, protein binding and cell cycle respectively. For downregulated-hypermethylated genes, the result was peptidyl-tyrosine phosphorylation, plasma membrane, transmembrane receptor protein tyrosine kinase activity and Rap1 signaling pathway (All p< 0.05). 12 hub genes (TOP2A, MAD2L1, FEN1, EPRS, EXO1, MCM4, PTTG1, RRM2, PSMD14, CDKN3, H2AFZ, CCNE2) were sorted from 677 upregulated-hypomethylated genes. 4 hub genes (EGFR, FGF2, BCL2, PIK3R1) were sorted from 361 downregulated-hypermethylated genes. Differential expression of 16 hub genes was validated in UALCAN database (p<0.05). 7 in 12 upregulated-hypomethylated and 2 in 4 downregulated-hypermethylated hub genes were confirmed to be significantly hypomethylated or hypermethylated in breast cancer using MethHC database (p<0.05). Finally, 12 upregulated hub genes (TOP2A, MAD2L1, FEN1, EPRS, EXO1, MCM4, PTTG1, RRM2, PSMD14, CDKN3, H2AFZ, CCNE2) and 3 downregulated genes (FGF2, BCL2, PIK3R1) contributed to significant unfavorable clinical outcome in breast cancer (p<0.05). High expression level of EXO1 protein was significantly associated with poor OS in breast cancer patients (p=0.03). Conclusion: Overexpression of TOP2A, MAD2L1, FEN1, EPRS, EXO1, MCM4, PTTG1, RRM2, PSMD14, CDKN3, H2AFZ, CCNE2 and downregulation of FGF2, BCL2, PIK3R1 might serve as diagnosis and poor prognosis biomarkers in breast cancer by more research validation. EXO1 was identified as an individual unfavorable prognostic factor. Methylation might be one of the major causes leading to abnormal expression of those genes. Functional analysis and pathway enrichment analysis of those genes would provide novel ideas for breast cancer research.
| S-EPMC6856906 | biostudies-literature
Project description:Uveal melanoma (UM) is the most common primary intraocular cancer in adults. In the present study, we aimed to characterize the immunological features of primary UM cancer and to provide an association with prognostic markers and outcome. Also, we assessed the influence of the microenvironment on the expression of inhibitory immune checkpoints in UM. Genes of interest included MHC Class I and Class II molecules, as well as inhibitory immune-checkpoints, i.e. PDL1, PDL2, B7-H3, B7-H4, TBFRSF6B, CD47, CD155, GAL9, HVEM and CD200. We observed significant lower levels of MHC genes in UM cells as compared to normal uveal melanocytes. Unexpectedly however, the expression levels of most of the analyzed inhibitory immune-checkpoint genes were not different in cancer cells as compared to normal melanocytes, with the exception of CD200 and HVEM, that resulted significantly reduced. On the other hand, PDL1 inversely correlated with OS, PFS and thickness of the tumor. Also, PDL1, along with PDL2, expression significantly increased under inflammatory conditions. Finally, for the first time, we propose a possible role for CD47 in the immune evasive properties of UM. We show here that CD47 is significantly upregulated by UM cells following inflammatory stimuli and that it represents a good independent predictor of disease progression. The results from this study may propel advances in the development of immune-based therapies for UM patients.
| S-EPMC6336329 | biostudies-literature
Project description:Digestive system neoplasms are the leading causes of cancer-related death all over the world. Solute carrier (SLC) superfamily is composed of a series of transporters that are ubiquitously expressed in organs and tissues of digestive systems and mediate specific uptake of small molecule substrates in facilitative manner. Given the important role of SLC proteins in maintaining normal functions of digestive system, dysregulation of these protein in digestive system neoplasms may deliver biological and clinical significance that deserves systemic studies. In this review, we critically summarized the recent advances in understanding the role of SLC proteins in digestive system neoplasms. We highlighted that several SLC subfamilies, including metal ion transporters, transporters of glucose and other sugars, transporters of urea, neurotransmitters and biogenic amines, ammonium and choline, inorganic cation/anion transporters, transporters of nucleotide, amino acid and oligopeptide organic anion transporters, transporters of vitamins and cofactors and mitochondrial carrier, may play important roles in mediating the initiation, progression, metastasis, and chemoresistance of digestive system neoplasms. Proteins in these SLC subfamilies may also have diagnostic and prognostic values to particular cancer types. Differential expression of SLC proteins in tumors of digestive system was analyzed by extracting data from human cancer database, which revealed that the roles of SLC proteins may either be dependent on the substrates they transport or be tissue specific. In addition, small molecule modulators that pharmacologically regulate the functions of SLC proteins were discussed for their possible application in the treatment of digestive system neoplasms. This review highlighted the potential of SLC family proteins as drug target for the treatment of digestive system neoplasms.
| S-EPMC5788932 | biostudies-literature
Project description:BackgroundEndometrial cancer is a common gynecological cancer with annually increasing incidence worldwide. However, the biomarkers that provide prognosis and progression for this disease remain elusive.ResultsTwo eligible human endometrial cancer datasets (GSE17025 and GSE25405) were selected for the study. A total of 520 differentially expressed mRNAs and 30 differentially expressed miRNAs were identified. These mRNAs were mainly enriched in cell cycle, skeletal system development, vasculature development, oocyte maturation, and oocyte meiosis signalling pathways. A total of 160 pairs of differentially expressed miRNAs and mRNAs, including 22 differentially expressed miRNAs and 71 overlapping differentially expressed mRNAs, were validated in endometrial cancer samples using starBase v2.0 project. The prognosis analysis revealed that Cyclin E1 (CCNE1, one of the 82 hub genes, which correlated with hsa-miR-195 and hsa-miR-424) was significantly linked to a worse overall survival in endometrial cancer patients.ConclusionsThe hub genes and differentially expressed miRNAs identified in this study might be used as prognostic biomarkers for endometrial cancer and molecular targets for its treatment.
| S-EPMC7510080 | biostudies-literature
Project description:IntroductionFor many tumors, the overexpression of the chemokine receptor CXCR4 is associated with increased malignancy and poor patient outcomes. However, comprehensive data for neuroendocrine neoplasms of the lung are still lacking.MethodsCXCR4 expression was evaluated in a panel of bronchopulmonary neuroendocrine neoplasms (BP-NEN) comprising typical carcinoids (n = 26), atypical carcinoids (n = 30), and small cell lung cancers (SCLC, n = 34). Samples were analyzed by immunohistochemistry using the novel monoclonal rabbit anti-human CXCR4 antibody UMB-2 and by qRT-PCR. The expression was correlated with clinical data and overall patient survival.ResultsCXCR4 was predominantly localized at the plasma membrane of the tumor cells. CXCR4 was expressed with a high intensity in almost all of the 30 SCLC samples. In contrast, it was detected infrequently and with low intensity in the typical carcinoid and atypical carcinoid samples. There was a significant correlation between the immunohistochemistry and qRT-PCR data. Additionally, there was a significant negative relationship between CXCR4 expression and overall survival.ConclusionsWith increasing malignancy, BP-NEN clearly differ in the extent of CXCR4 expression. As in other tumor entities, CXCR4 overexpression significantly correlates with negative patient outcome. Due to its particular high expression rate in SCLC, CXCR4 may serve as a promising new target for diagnostic and pharmacological intervention as well as for peptide receptor-based radionuclide therapy.
| S-EPMC4413658 | biostudies-literature
Project description:Friend Leukemia Virus Integration 1 (FLI-1) is a member of E26 transformation-specific family of transcription factors that participates in hematopoietic and vascular endothelial cell development. Immunohistochemical detection of FLI-1 has been widely used to diagnose vascular tumors or, more evidently, Ewing's sarcoma. However, the expression pattern of FLI-1 in hematolymphoid neoplasms remains unclear. Therefore, in this study, we aimed to investigate the expression of FLI-1 in these tumors, focusing on high-grade lesions, which presents a diagnostic challenge by mimicking Ewing's sarcoma. We evaluated the expression FLI-1 in various types of lymphoid and plasmacytic tumors, including 27 plasmablastic lymphomas, 229 diffuse large B-cell lymphomas, 22 precursor T- or B-lymphoblastic lymphomas, 24 angioimmunoblastic-type nodal T-follicular helper cell lymphomas, 52 peripheral T-cell lymphomas, NOS, 18 Burkitt lymphomas, 18 non-gastric lymphomas of mucosa-associated lymphoid tissue, 38 chronic lymphocytic leukemia/small lymphocytic lymphomas, 15 mantle cell lymphomas, 23 gastric MALT lymphomas, 50 plasma cell myelomas, and 38 follicular lymphomas. We calculated the H-scores of FLI-1 immunostaining, ranging from 0 to 200, and used the scores to analyze the clinicopathological significance of FLI-1 statistically. FLI-1 was expressed to varying degrees in all types of hematological tumors. FLI-1 expression was detected in 84.1% of patients (466/554). FLI-1 was highly expressed in precursor T- or B-lymphoblastic lymphomas. Follicular lymphomas exhibited low FLI-1 expression. In plasmablastic lymphoma, 85.2% of the patients were focally positive for FLI-1. FLI-1 expression did not correlate with clinicopathological variables, such as demographic data or disease stage, in patients with plasmablastic lymphoma and diffuse large B-cell lymphoma. However, FLI-1 overexpression was associated with poorer overall survival in patients with plasmablastic lymphoma. This study demonstrates that FLI-1 is expressed in various hematolymphoid neoplasms. FLI-1 expression can lead to diagnostic confusion, especially in small blue round cell tumors, such as lymphoblastic lymphoma, plasmablastic lymphoma, and plasma cell myeloma, when distinguishing tumors positive for CD99 and CD56 without CD3, CD20, or CD45. Our findings also suggested the possibility of FLI-1 as a potential prognostic biomarker for plasmablastic lymphoma.
| S-EPMC10821826 | biostudies-literature