Association of Albumin-Corrected Serum Calcium Levels with Colorectal Cancer Survival Outcomes.

In epidemiological studies, higher calcium intake has been associated with decreased colorectal cancer (CRC) incidence. However, whether circulating calcium concentrations are associated with CRC prognosis is largely unknown. In this retrospective cohort analysis, we identified 498 patients diagnosed with stage I-IV CRC between the years of 2000 and 2018 in whom calcium and albumin level measurements within 3 months of diagnosis had been taken. We used the Kaplan-Meier method for survival analysis. We used multivariate Cox proportional hazards regression to identify associations between corrected calcium levels and CRC survival outcomes. Corrected calcium levels in the highest tertile were associated with significantly lower progression-free survival rates (hazard ratio (HR) 1.85; 95% confidence interval (CI) 1.28-2.69; p = 0.001) and overall survival (HR 1.86; 95% CI 1.26-2.74, p = 0.002) in patients with stage IV or recurrent CRC, and significantly lower disease-free survival rates (HR 1.44; 95% confidence interval (CI) 1.02-2.03; p = 0.040) and overall survival rates (HR 1.72; 95% CI 1.18-2.50; p = 0.004) in patients with stage I-III disease. In conclusion, higher corrected calcium levels after the diagnosis of CRC were significantly associated with decreased survival rates. Prospective trials are necessary to confirm this association.

Physiologic IGFBP7 levels prolong IGF1R activation in acute lymphoblastic leukemia.

Insulin and insulin-like growth factors (IGFs) are mitogenic and prosurvival factors to many different cell types, including acute lymphoblastic leukemia (ALL). Circulating IGFs are bound by IGF binding proteins (IGFBPs) that regulate their action. IGFBP7 is an IGFBP-related protein (IGFBP-rP) that in contrast to other IGFBPs/IGFBP-rPs features higher affinity for insulin than IGFs and was shown to bind the IGF1 receptor (IGF1R) as well. The role of IGFBP7 in cancer is controversial: on some tumors, it functions as an oncogene, whereas in others, it functions as a tumor suppressor. In childhood ALL, higher IGFBP7 expression levels were associated with worse prognosis. Here we show that IGFBP7 exerts mitogenic and prosurvival autocrine effects on ALL cells that were dependent on insulin/IGF. IGFBP7 knockdown or antibody-mediated neutralization resulted in significant attenuation of ALL cell viability in vitro and leukemia progression in vivo. IGFBP7 was shown to prolong the surface retention of the IGF1R under insulin/IGF1 stimulation, resulting in sustained IGF1R, insulin receptor substrate 1 (IRS-1), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) phosphorylation. Conversely, the insulin receptor was readily internalized and dephosphorylated on insulin stimulation, despite IGFBP7 addition. The affinity of homodimeric IGF1R for insulin is reportedly >100 times lower than for IGF1. In the presence of IGFBP7, however, 25 ng/mL insulin resulted in IGF1R activation levels equivalent to that of 5 ng/mL IGF1. In conclusion, IGFBP7 plays an oncogenic role in ALL by promoting the perdurance of IGF1R at the cell surface, prolonging insulin/IGF stimulation. Preclinical data demonstrate that IGFBP7 is a valid target for antibody-based therapeutic interventions in ALL.

Adipose tissue radiodensity: A new prognostic biomarker in people with multiple myeloma.

OBJECTIVES: Standard prognostic markers based on individual characteristics of individuals with multiple myeloma (MM) remain scarce. Body-composition features have often been associated with survival outcomes in different cancers. However, the association of adipose tissue radiodensity with MM prognosis has not yet, to our knowledge, been explored. METHODS: Computed tomography at the third lumbar vertebra was used for body-composition analysis, including adipose tissue radiodensity, in 91 people with MM. Additionally, fludeoxyglucose F 18 (18F-FDG) positron emission tomography was used to assess adipose tissue 18F-FDG uptake. Proinflammatory cytokine and adipokine levels were measured. RESULTS: Event-free survival and overall survival were both shorter in participants with high subcutaneous adipose tissue (SAT) radiodensity. Those in the highest SAT radiodensity tertile had an independently higher risk for both overall survival (hazard ratio, 4.55; 95% confidence interval, 1.26-16.44; Ptrend = 0.036) and event-free survival (hazard ratio, 3.08; 95% confidence interval, 1.02-9.27; Ptrend = 0.035). Importantly, higher SAT radiodensity was significantly correlated with increased 18F-FDG adipose tissue uptake and proinflammatory cytokine (tumor necrosis factor and interleukin-6) levels, and with decreased leptin levels. CONCLUSIONS: SAT radiodensity may serve as a biomarker to predict host-related metabolic and proinflammatory milieu, which ultimately correlates with MM prognosis.

Visceral adipose tissue glucose uptake is linked to prognosis in multiple myeloma patients: An exploratory study.

BACKGROUND & AIMS: The use of computerized tomography to opportunistically assess body composition has highlighted abnormalities such as low muscle mass and high adiposity may be hidden conditions in cancer patients. However, the role of skeletal muscle (SM), subcutaneous (SAT) and visceral (VAT) adipose tissue glucose uptake measured by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-CT on patient prognostication is unclear. METHODS: Patients with multiple myeloma (MM) with satisfactory image frame for assessing body composition and for semi-quantification of SM, SAT and VAT glucose uptakes were included. Plasmatic pro-inflammatory cytokine and adipokine levels were measured. RESULTS: High VAT mean standardized uptake value (SUV) at baseline was associated with shorter event-free survival (EFS) (hazard ratio [HR]: 7.89; 95% confidence interval [CI], 1.58-39.30; P = 0.012) and overall survival (OS) (HR, 15.24; 95% CI, 2.69-86.30; P = 0.002) among patients with newly diagnosed MM, even after adjustment for covariates. The highest tertile of VAT SUV was significantly correlated with worse MM-EFS (HR for the highest vs the lowest tertile 3.71; 95% CI, 1.22-10.56; Ptrend = 0.035) and mortality (HR, 4.41; 95% CI, 1.28-12.77; Ptrend = 0.019). Notably, patients with higher VAT SUV presented with lower VAT area, VAT index, higher SAT SUV, and higher number of individuals with visceral obesity (all P < 0.01). Additionally, we found a negative correlation between VAT mean SUV with leptin (R2 = 0.20, P = 0.003); no correlations were detected between VAT mean SUV and resistin, tumor necrosis factor (TNF) or interleukin (IL)-6. CONCLUSIONS: Functional VAT activity estimated by 18F-FDG PET-CT is a relevant prognostic factor in MM patients, specifically, a higher VAT SUV might be an early biomarker of cancer cachexia in these patients.