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Prognostic significance of circulating insulin growth-like factor 1 and insulin growth-like factor binding protein 3 in renal cell carcinoma patients.

ABSTRACT: Insulin growth-like factor-1 (IGF-1) and its main binding protein insulin growth-like factor binding protein 3 (IGFBP-3) play important roles in cancer development and progression. We hypothesize that circulating IGF-1 and IGFBP-3 may have significant prognostic values in renal cell carcinoma (RCC) patients. We used 1,010 histologically confirmed RCC patients in this case series study to test this hypothesis. We constructed a weighted genetic risk score (GRS) using a large panel of genome-wide association study (GWAS)-identified single nucleotide polymorphisms (SNPs) to predict circulating IGF-1 and IGFBP-3 level, respectively. We analyzed the associations of the GRS with the prognosis of RCC patients using multivariate Cox proportional hazards model. We found significant associations between genetically predicted circulating IGF-1 level, but not IGFBP-3, and RCC prognosis. RCC patients with better prognosis had significantly higher baseline circulating IGF-1 level than those with worse prognosis. Dichotomized at the median value of GRS, patients with high IGF-1 exhibited significantly lower risks of recurrence (HR=0.81, 95% CI, 0.65-0.99, P=0.045) and death (HR=0.74, 95% CI, 0.60-0.91, P=0.004). If patients were dichotomized at the 75% value of GRS, those with the highest quarter of GRS had 27% lower risk of recurrence (OR=0.73, 95% CI, 0.55-0.96, P=0.025) and 34% lower risk of death (OR=0.66, 95% CI, 0.50-0.87, P=0.003) than the other three quarters of patients. High IGF-1/IGFBP-3 ratio was also associated with reduced risks of recurrence and survival. In conclusion, high circulating IGF-1 level and IGF-1/IGFBP-3 ratio at diagnosis is associated with better prognosis in RCC patients.

SUBMITTER: Tsai CW

PROVIDER: S-EPMC8899987 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Prognostic significance of circulating insulin growth-like factor 1 and insulin growth-like factor binding protein 3 in renal cell carcinoma patients.

Tsai Chia-Wen CW Chang Wen-Shin WS Xu Yifan Y Huang Maosheng M Tamboli Pheroze P Wood Christopher G CG Bau Da-Tian DT Gu Jian J

American journal of cancer research 20220215 2

Insulin growth-like factor-1 (IGF-1) and its main binding protein insulin growth-like factor binding protein 3 (IGFBP-3) play important roles in cancer development and progression. We hypothesize that circulating IGF-1 and IGFBP-3 may have significant prognostic values in renal cell carcinoma (RCC) patients. We used 1,010 histologically confirmed RCC patients in this case series study to test this hypothesis. We constructed a weighted genetic risk score (GRS) using a large panel of genome-wide a ...[more]

PMID: 35261807

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Project description:To characterize predictors of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in acute critical illness with the hypothesis that acute factors associated with critical illness will more strongly predict circulating insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 than chronic clinical or genetic factors.Observational study nested within a large prospective study using multivariable linear regression to model circulating insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 with acute and chronic clinical variables, and genotype from five polymorphisms in insulin-like growth factor pathway genes.ICUs from two large academic medical centers.Five hundred forty-three Caucasian patients with risk factors for acute respiratory distress syndrome and available plasma from early in critical illness.None.Total insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 were measured in plasma using IMMULITE assays (Siemens, Malvern, PA). We examined age, gender, body mass index, cirrhosis, and diabetes, as well as Acute Physiology, Age, and Chronic Health Evaluation III score, acute hepatic dysfunction, pneumonia and aspiration, sepsis/septic shock, acute respiratory distress syndrome, and receipt of corticosteroids. Body mass index, cirrhosis, and acute respiratory distress syndrome were strongly associated with insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels; Acute Physiology, Age, and Chronic Health Evaluation III was strongly associated with insulin-like growth factor-1 levels; and age was strongly associated with insulin-like growth factor-binding protein-3. Five polymorphisms (IGF1: rs1520220, rs35767, rs2946834; IGFBP1: rs4619; IGFBP3: rs2854746) were analyzed for associations with plasma levels. When genotypes were added to models, rs2854746 was significantly associated with plasma insulin-like growth factor-binding protein-3. Genotype explained an additional 2% of variability with an overall adjusted R-square of 0.18.Despite the acute derangements of critical illness, both acute and chronic health factors significantly influence circulating levels of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 early in critical illness. rs2854746 is also significantly associated with insulin-like growth factor-binding protein-3 levels in this ICU cohort. Overall, phenotypic and genotypic factors explained only a modest amount of variability in insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. Further research is needed to understand how to apply these findings to patient care.

Project description:BackgroundPancreatic adenocarcinoma (PAAD) is a highly aggressive cancer with poor prognosis and limited therapeutic options. Identifying molecular markers and understanding their role in PAAD pathogenesis is crucial for developing targeted therapies. This study integrates bioinformatics and molecular experiments to investigate the diagnostic, prognostic, and therapeutic significance of FGFBP1 in PAAD.MethodsUALCAN, TNMplot, OncoDB, GEPIA2, HPA, GSCA, KM Plotter, TISIDB, TISCH2, CancerSEA, STRING, DAVID, cell culture, RT-qPCR analysis, western blot analysis, colony formation, cell proliferation, and wound healing assays.ResultsExpression analyses revealed a significantly elevated FGFBP1 levels in PAAD tissues compared to normal samples. Promoter methylation analysis indicated lower methylation levels in PAAD, inversely correlated with FGFBP1 expression, suggesting epigenetic regulation. Genetic alteration analysis showed that FGFBP1 is not significantly affected by single nucleotide variants, but copy number variations are present without impacting mRNA expression. Survival analysis using KM plotter demonstrated that high FGFBP1 expression is associated with poor overall and disease-free survival. A Cox regression-based prognostic model confirmed the negative impact of elevated FGFBP1 on patient outcomes. Correlation analysis with immune-related factors indicated that FGFBP1 may contribute to an immunosuppressive tumor microenvironment, affecting immune cell infiltration and function. Single-cell analysis highlighted FGFBP1 expression in malignant, endothelial, and fibroblast cells within the tumor microenvironment. Gene enrichment analysis revealed FGFBP1's involvement in various biological processes and pathways related to cancer progression. Experimental validation using RT-qPCR confirmed high FGFBP1 expression in PAAD cell lines. FGFBP1 knockdown in HEK293T cells significantly reduced cell proliferation, colony formation, and migration.ConclusionThese findings suggest that FGFBP1 plays a critical role in PAAD pathogenesis and could serve as a potential therapeutic target for improving patient outcomes.

Dataset Information

Prognostic significance of circulating insulin growth-like factor 1 and insulin growth-like factor binding protein 3 in renal cell carcinoma patients.

Publications

Prognostic significance of circulating insulin growth-like factor 1 and insulin growth-like factor binding protein 3 in renal cell carcinoma patients.

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