Pre-diagnostic biomarkers of metabolic dysregulation and cancer mortality

Abstract

INTRODUCTIONThe obesogenic milieu is a pro-tumorigenic environment that promotes tumor initiation, angiogenesis and metastasis. In this prospective cohort, we examined the association between pre-diagnostic metabolic biomarkers, plasma adiponectin, resistin, leptin and lipoprotein (a), and the risk of cancer mortality.METHODSProspective data was obtained from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of Blacks and Whites followed from 2003 through 2012 for cancer mortality. We determined the association between metabolism biomarkers (log-transformed and tertiles) and risk of cancer mortality using Cox Proportional Hazards models with robust sandwich estimators to calculate the 95% confidence intervals (CIs), and adjusted for baseline covariates, including age, gender, income, education, physical activity, BMI, smoking status, alcohol use, and comorbidity score.RESULTSAmong 1764 participants with available biomarker data, each SD higher log-leptin was associated with a 54% reduced risk of total cancer mortality (HR: 0.46, 95% CI: 0.23 – 0.92) and obesity-related cancer mortality (HR: 0.55, 95% CI: 0.39-0.79). Among Blacks only, each SD higher log-resistin was associated with a nearly 7-fold increased risk of cancer mortality (adjusted HR: 6.68, 95% CI: 2.10 – 21.21). There were no significant associations of adiponectin or Lp(a) and cancer mortality.CONCLUSIONSLeptin is involved in long-term regulation of energy balance, while resistin is involved in chronic inflammation and LDL production. These findings highlight the biological mechanisms linking metabolic dysregulation with cancer mortality, and the influence of resistin on cancer mortality only among Blacks suggests that this hormone may be a useful biomarker of racial differences in cancer mortality that deserves further study.IMPACTOur observed increased risk of cancer mortality associated with higher serum resistin levels among Blacks suggests that if validated in larger cohorts, clinical strategies focused on resistin control may be a promising cancer prevention strategy.

Hyperresistinemia in Obese Female Dogs With Mammary Carcinoma in Benign-Mixed Tumors and Its Correlation With Tumor Aggressiveness and Survival

“…In an evaluation of women with breast neoplasms, a lower survival rate, in addition to a worse prognostic factor was observed in females with higher body weights ( 66 ), while a significantly higher proportion of undifferentiated tumors (grade III) in obese dogs, with consequent lower survival, was observed in another study ( 24 ). In fact, the greater number of deaths of obese dogs in the CBMT group combined with the higher values of serum resistin in the present study is relevant, since it corresponds to literature data showing a lower life expectancy and prognosis in women under equivalent conditions ( 16 , 17 ). The results herein obtained with the univariate and multivariate analyses revealed that, as observed in women ( 50 , 51 ), there was a positive association between hyperresistinemia, BMIc, and %BF in dogs of the CBMT group that presented higher rates of tumor proliferation and lower survival, indicating the participation of this adipocytokine in tumor aggressiveness.…”

“…Adipocytokines have been widely studied because they participate in mechanisms of cell proliferation, adhesion, and invasion, thus playing an important role in the development and progression of breast tumors ( 17 , 18 ). However, little is known about the participation of resistin in mammary tumors in dogs.…”

“…There is a possibility that there are some mechanisms related to this process in patients with breast cancer, like upregulation of proinflammatory cytokines via the NF-κB pathway, an important component of cancer-promoting machinery ( 60 ). In addition, the higher the resistin concentration, the worse the malignancy, tumor stage, size, and presence of metastasis ( 16 , 17 ), what justifies why it is considered a promising biomarker for breast tumor prognosis ( 18 , 19 , 61 ).…”

“…Although this correlation is not well-understood, it is known that resistin promotes epithelial and mesenchymal multiplication in the breast parenchyma, which are critical mechanisms for tumor development and metastasis ( 16 ). In addition, resistin concentrations are positively correlated with malignancy, tumor stage and size and presence of metastasis ( 16 , 17 ), which makes this molecule a biomarker for breast tumor prognosis ( 18 , 19 ).…”

Serum RNA Profiling in the 10-Years Period Prior to Diagnosis of Testicular Germ Cell Tumor

“…For germ cell neoplasia in situ (GCNIS), the markers include OCT3/4, PLAP, CD117, and SALL 4 (17). Furthermore, it has been shown that the metabolic biomarkers leptin and resisting may predict cancer mortality due to their function of inducing pro-tumorigenic environment that further promotes tumor initiation, angiogenesis, and metastasis (22).…”