Parathyroid hormone related protein (PTHrP) in patients with pancreatic carcinoma and overt signs of disease progression and host tissue wasting

Britt-Marie Iresjö; Serkan Kir; Kent Lundholm

doi:10.1016/j.tranon.2023.101752

Parathyroid hormone related protein (PTHrP) in patients with pancreatic carcinoma and overt signs of disease progression and host tissue wasting

Transl Oncol. 2023 Oct:36:101752. doi: 10.1016/j.tranon.2023.101752. Epub 2023 Aug 2.

Authors

Britt-Marie Iresjö¹, Serkan Kir², Kent Lundholm³

Affiliations

¹ Surgical Metabolic Research Lab, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden. Electronic address: britt-marie.iresjo@surgery.gu.se.
² Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Molecular Biology and Genetics, KoÇ University, Istanbul 34450, Turkey.
³ Surgical Metabolic Research Lab, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden; Department of Surgery, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg 41345, Sweden.

Abstract

Background: Cancer-cachexia is a complex syndrome secondary to physiological mechanisms related to classical hormone and immune alterations, where contributions of neuro-endocrine involvement have been less evaluated. Therefore, the aim of our study was to explore relationships between PTHrP and whole body metabolism in patients with progressive pancreatic carcinoma; relevant to "fat tissue browning".

Methods: Patient serum samples and clinical information were retrieved from earlier translational projects (1995-2005), at Sahlgrenska University Hospital in Gothenburg. Blood PTHrP levels were determined at Harvard medical School (2014). Patient data included: medical history, clinical laboratory tests, food diaries, resting metabolic expenditure, body composition, exercise capacity, Health-Related Quality of Life (SF-36) and mental disorders (HAD-scales).

Results: Serum PTHrP was detectable in 17 % of all samples without significance to tumor stage. PTHrP-negativity at inclusion remained during follow-up. Mean PTHrP concentration was 262±274 pg/ml, without sex difference and elevation over time. PTHrP-positive and negative patients experienced similar body weight loss (%) at inclusion, with a trend to deviate at follow ups (16.8±8.2% vs. 13.1±8.2%, p<0.06), where PTHrP concentrations showed correlations to weight loss, handgrip strength and Karnofsky performance, without difference in exercise capacity. PTHrP-positivity was related to increased whole body fat oxidation (p<0.006-0.01) and reduced carbohydrate oxidation (p<0.01-0.03), independently of peripheral lipolysis. Metabolic alterations in PTHrP-positive patients were related to reduced Health Related Quality of life (SF: p<0.08, MH: p<0.02), and increased anxiety and depression (HAD 1-7: p<0.004; HAD 8-14: p<0.008).

Conclusion: Serum PTHrP positivity in patients with pancreatic carcinoma was related to altered whole body oxidative metabolism; perhaps induced by "browning" of fat cells?

Keywords: Cachexia; Oxidative metabolism; PTHrP; Pancreatic cancer.