Serum PTHrP Predicts Weight Loss in Cancer Patients Independent of Hypercalcemia, Inflammation, and Tumor Burden

• Published in: The journal of clinical endocrinology and metabolism Vol. 101; no. 3; pp. 1207 - 1214
• Main Authors: Hong, Namki, Yoon, Hye-jin, Lee, Yong-ho, Kim, Hye Ryun, Lee, Byung Wan, Rhee, Yumie, Kang, Eun Seok, Cha, Bong-Soo, Lee, Hyun Chul
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.03.2016; Copyright by The Endocrine Society
• Subjects: Aged; Body mass index; C-reactive protein; Cachexia; Cachexia - blood; Cachexia - diagnosis; Cachexia - etiology; Cancer; Comorbidity; Energy expenditure; Female; Humans; Hypercalcemia; Hypercalcemia - blood; Hypercalcemia - complications; Inflammation; Inflammation - blood; Inflammation - complications; Longitudinal Studies; Male; Middle Aged; Neoplasms - blood; Neoplasms - complications; Neoplasms - diagnosis; Parathyroid hormone-related protein; Parathyroid Hormone-Related Protein - blood; Prognosis; Serum levels; Tumor Burden - physiology; Tumors; Weight; Weight Loss
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2015-3785

Context:Recent animal studies showed that tumor-derived PTHrP induced cancer cachexia by fat browning with increased energy expenditure; however, clinical evidence from human data is insufficient.Objective:We investigated whether serum PTHrP levels independently predicts weight loss (WL) in cancer patients.Design, Setting, and Patients:From a longitudinal observational cohort, body mass index (BMI) of patients with measured serum PTHrP levels (n = 624) was assessed (median follow-up of 327 d).Main Outcome Measures:Cox hazard models were used to examine the predictive value of PTHrP for WL defined by consensus definition (WL [consensus], percentage WL < −5% or percentage WL < −2% plus BMI < 20 kg/m2) and by BMI-adjusted grades (WL [BMI adjusted]).Results:The overall risk of WL (consensus) was 34.4%. Compared with PTHrP-negative subjects, patients with higher PTHrP levels (PTHrP ≥ median 5.7 pmol/L) had more WL (percentage WL, −6.9% vs −1.1%, P = .010) at follow-up. A higher PTHrP level was associated with an increased loss of body weight (β = −2.73), muscle (β = −1.85), and fat (β = −2.52) after controlling for age, sex, and BMI. Kaplan-Meier analysis demonstrated that subjects with higher PTHrP had increased WL risk compared with lower PTHrP or PTHrP-negative groups (52.0% vs 38.9% vs 29.7%, P < .001). Serum PTHrP was independently associated with an increased WL risk (hazard ratio [HR]1.23, P = .005) adjusted for potent predictors including serum levels of calcium, C-reactive protein, albumin, cancer stage, and performance status of patients. Consistent results were observed when BMI-adjusted WL was applied.Conclusions:Serum PTHrP levels predicted cancer-associated WL independent of the presence of hypercalcemia, inflammation, tumor burden, and other comorbidities.