Dataset Information

Differential roles of highly expressed PFKFB4 in colon adenocarcinoma patients.

ABSTRACT: Colon adenocarcinoma (COAD) is a common malignant tumor, and the role of the protein PFKFB4 in glycolysis and pentose phosphate pathways is crucial. Researchers investigated the clinical significance of PFKFB4 in COAD by studying its expression in 79 tissue samples using immunohistochemistry. We found that PFKFB4 expression was significantly higher in COAD patients, particularly in the sigmoid colon. Interestingly, high PFKFB4 expression was associated with both improved overall survival (OS) and worse progression-free survival (PPS) in COAD patients. Further analysis revealed that genes associated with PFKFB4 were linked to various metabolic pathways, including amino acid biosynthesis, glycolysis, gluconeogenesis, glucose metabolism, and inflammatory response. PFKFB4 expression also showed correlations with the infiltration of different immune cell types in COAD patients, such as CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), macrophages, neutrophils, dendritic cells, active mast cells, and resting NK cells. Overall, the relationship between PFKFB4 expression and the prognosis of COAD is complex and diverse, possibly playing different roles at different stages of the disease. Moreover, its mechanism might involve interactions with various metabolic pathways and immune infiltration in the tumor microenvironment. These findings provide valuable insights into the potential role of PFKFB4 as a biomarker or therapeutic target in COAD.

SUBMITTER: Gu X

PROVIDER: S-EPMC10539362 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Differential roles of highly expressed PFKFB4 in colon adenocarcinoma patients.

Gu Xiaojing X Dai Xingchen X Huang Yongli Y Zhang Yuhuan Y Dong Lintao L Gao Chanchan C Wang Fang F

Scientific reports 20230928 1

Colon adenocarcinoma (COAD) is a common malignant tumor, and the role of the protein PFKFB4 in glycolysis and pentose phosphate pathways is crucial. Researchers investigated the clinical significance of PFKFB4 in COAD by studying its expression in 79 tissue samples using immunohistochemistry. We found that PFKFB4 expression was significantly higher in COAD patients, particularly in the sigmoid colon. Interestingly, high PFKFB4 expression was associated with both improved overall survival (OS) an ...[more]

PMID: 37770581

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Project description:BackgroundColon adenocarcinoma (COAD) can be divided into left-sided and right-sided COAD (LCCs and RCCs, respectively). They have unique characteristics in various biological aspects, particularly immune invasion and prognosis. The purpose of our study was to develop a prognostic risk scoring model (PRSM) based on differentially expressed immune-related genes (IRGs) between LCCs and RCCs, therefore the prognostic key IRGs could be identified.MethodsThe gene sets and clinical information of COAD patients were derived from TCGA and GEO databases. The comparison of differentially expressed genes (DEGs) of LCCs and RCCs were conducted with appliance of "Limma" analysis. The establishment about co-expression modules of DEGs related with immune score was conducted by weighted gene co-expression network analysis (WGCNA). Furthermore, we screened the module genes and completed construction of gene pairs. The analysis of the prognosis and the establishment of PRSM were performed with univariate- and lasso-Cox regression. We employed the PRSM in the model group and verification group for the purpose of risk group assignment and PRSM accuracy verification. Finally, the identification of the prognostic key IRGs was guaranteed by the adoption of functional enrichment, "DisNor" and protein-protein interaction (PPI).ResultsA total of 215 genes were screened out by differential expression analysis and WGCNA. A PRSM with 16 immune-related gene pairs (IRGPs) was established upon the genes pairing. Furthermore, we confirmed that the risk score was an independent factor for survival by univariate- and multivariate-Cox regression. The prognosis of high-risk group in model group (P < 0.001) and validation group (P = 0.014) was significantly worse than that in low-risk group. Treg cells (P < 0.001) and macrophage M0 (P = 0.015) were highly expressed in the high-risk group. The functional analysis indicated that there was significant up-regulation with regard of lymphocyte and cytokine related terms in low-risk group. Finally, we identified five prognostic key IRGs associated with better prognosis through PPI and prognostic analysis, including IL2RB, TRIM22, CIITA, CXCL13, and CXCR6.ConclusionThrough the analysis and screening of the DEGs between LCCs and RCCs, we constructed a PRSM which could predicate prognosis of LCCs and RCCs, and five prognostic key IRGs were identified as well. Therefore, the basis for identifying the benefits of immunotherapy and immunomodulatory was built.

Project description:BackgroundColon adenocarcinoma (COAD) is a highly heterogeneous disease, which makes its prognostic prediction challenging. The purpose of this study was to investigate the clinical epidemiological characteristics, prognostic factors, and survival outcomes of patients with COAD in order to establish and validate a predictive clinical model (nomogram) for these patients.MethodsUsing the SEER (Surveillance, Epidemiology, and End Results) database, we identified patients diagnosed with COAD between 1983 and 2015. Disease-specific survival (DSS) and overall survival (OS) were assessed using the log-rank test and Kaplan-Meier approach. Univariate and multivariate analyses were performed using Cox regression, which identified the independent prognostic factors for OS and DSS. The nomograms constructed to predict OS were based on these independent prognostic factors. The predictive ability of the nomograms was assessed using receiver operating characteristic (ROC) curves and calibration plots, while accuracy was assessed using decision curve analysis (DCA). Clinical utility was evaluated with a clinical impact curve (CIC).ResultsA total of 104,933 patients were identified to have COAD, including 31,479 women and 73,454 men. The follow-up study duration ranged from 22 to 88 months, with an average of 46 months. Multivariate Cox regression analysis revealed that age, gender, race, site_recode_ICD, grade, CS_tumor_size, CS_extension, and metastasis were independent prognostic factors. Nomograms were constructed to predict the probability of 1-, 3-, and 5-year OS and DSS. The concordance index (C-index) and calibration plots showed that the established nomograms had robust predictive ability. The clinical decision chart (from the DCA) and the clinical impact chart (from the CIC) showed good predictive accuracy and clinical utility.ConclusionIn this study, a nomogram model for predicting the individualized survival probability of patients with COAD was constructed and validated. The nomograms of patients with COAD were accurate for predicting the 1-, 3-, and 5-year DSS. This study has great significance for clinical treatments. It also provides guidance for further prospective follow-up studies.

Dataset Information

Differential roles of highly expressed PFKFB4 in colon adenocarcinoma patients.

Publications

Differential roles of highly expressed PFKFB4 in colon adenocarcinoma patients.

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