title: Serum PTHrP Predicts Weight Loss in Cancer Patients Independent of Hypercalcemia, Inflammation, and Tumor Burden.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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/m(2)) 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.
authors.affiliation: Department of Internal Medicine (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), Severance Hospital (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), and Graduate School (N.H., Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; and Institute of Endocrine Research (Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), and Yonsei Cancer Center (H.R.K.), Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Namki
authors.initials: N
authors.lastname: Hong
authors.affiliation: Department of Internal Medicine (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), Severance Hospital (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), and Graduate School (N.H., Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; and Institute of Endocrine Research (Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), and Yonsei Cancer Center (H.R.K.), Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), Severance Hospital (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), and Graduate School (N.H., Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; and Institute of Endocrine Research (Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), and Yonsei Cancer Center (H.R.K.), Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Yong-Ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), Severance Hospital (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), and Graduate School (N.H., Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; and Institute of Endocrine Research (Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), and Yonsei Cancer Center (H.R.K.), Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Hye Ryun
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), Severance Hospital (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), and Graduate School (N.H., Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; and Institute of Endocrine Research (Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), and Yonsei Cancer Center (H.R.K.), Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Byung Wan
authors.initials: BW
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), Severance Hospital (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), and Graduate School (N.H., Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; and Institute of Endocrine Research (Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), and Yonsei Cancer Center (H.R.K.), Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Yumie
authors.initials: Y
authors.lastname: Rhee
authors.affiliation: Department of Internal Medicine (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), Severance Hospital (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), and Graduate School (N.H., Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; and Institute of Endocrine Research (Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), and Yonsei Cancer Center (H.R.K.), Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Eun Seok
authors.initials: ES
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), Severance Hospital (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), and Graduate School (N.H., Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; and Institute of Endocrine Research (Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), and Yonsei Cancer Center (H.R.K.), Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Bong-Soo
authors.initials: BS
authors.lastname: Cha
authors.affiliation: Department of Internal Medicine (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), Severance Hospital (N.H., H.Y., Y.L., H.R.K., B.W.L., Y.R., E.S.K., B.-S.C., H.C.L.), and Graduate School (N.H., Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; and Institute of Endocrine Research (Y.L., B.W.L., Y.R., E.S.K., B.-S.C.), and Yonsei Cancer Center (H.R.K.), Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
mesh_terms: D000368:Aged; D002100:Cachexia / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood* / Q000150:complications; D007249:Inflammation / Q000097:blood* / Q000150:complications; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D044162:Parathyroid Hormone-Related Protein / Q000097:blood*; D011379:Prognosis; D047368:Tumor Burden / Q000502:physiology*; D015431:Weight Loss
chemical_list: D044162:Parathyroid Hormone-Related Protein