Growth differentiating factor-15 (GDF-15)

A potential biomarker and therapeutic target for cancer-associated weight loss

Lorena Lerner, Jeno Gyuris, Richard Nicoletti, James Gifford, Brian Krieger, Aminah Jatoi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Growth differentiating factor-15 (GDF-15), also known as macrophage inhibiting factor-1, is a member of the transforming growth factor-β superfamily, which has been implicated in cancer-associated weight loss. The present study investigated the association between cancer-associated weight loss and plasma GDF-15 concentration, as well as other biomarkers, in patients with metastatic lung or exocrine pancreatic cancer. A total of 218 patients were enrolled over a 1-year period. The patient cohort included 152 patients with incurable lung cancer and 66 patients with incurable pancreatic cancer. Of the 218 patients, 98 (45%) reported >5% weight loss, 62 (28%) reported ≤5% weight loss and 58 (27%) reported no weight loss in the 6 months prior to diagnosis. In lung cancer patients, higher circulating GDF-15 levels were significantly associated with weight loss; lung cancer patients who reported >5% weight loss (n=56) were found to exhibit twice the circulating concentration of GDF-15 compared with those that exhibited no weight loss (n=48) (P<0.0001). Additional mediators, including Activin A, interleukin (IL)-12, vascular endothelial growth factor A, IL-1 receptor α, eotaxin and platelet derived growth factor-BB, were also associated with weight loss; however, the associations were not as strong. In pancreatic cancer patients, no association between GDF-15 levels and weight loss was identified. However, higher circulating GDF-15 levels were consistently associated with poor survival in univariate [hazard ratio (HR), 1.13; 95% confidence interval (CI), 1.02-1.23; P=0.016] and multivariate [HR, 1.1; 95% CI, 1.02-1.24; P=0.03] analysis, respectively. Thus, GDF-15 requires further study as a biomarker and potential therapeutic target in cancer-associated weight loss, particularly in lung cancer patients.

Original languageEnglish (US)
Pages (from-to)4219-4223
Number of pages5
JournalOncology Letters
Volume12
Issue number5
DOIs
StatePublished - Nov 1 2016

Fingerprint

Weight Loss
Intercellular Signaling Peptides and Proteins
Biomarkers
Neoplasms
Lung Neoplasms
Pancreatic Neoplasms
Therapeutics
Confidence Intervals
Interleukin-1 Receptors
Transforming Growth Factors
Interleukin-12
Vascular Endothelial Growth Factor A
Macrophages
Lung
Survival

Keywords

  • Cancer
  • Growth differentiating factor-15
  • Therapeutic target
  • Weight loss

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Growth differentiating factor-15 (GDF-15) : A potential biomarker and therapeutic target for cancer-associated weight loss. / Lerner, Lorena; Gyuris, Jeno; Nicoletti, Richard; Gifford, James; Krieger, Brian; Jatoi, Aminah.

In: Oncology Letters, Vol. 12, No. 5, 01.11.2016, p. 4219-4223.

Research output: Contribution to journalArticle

Lerner, Lorena ; Gyuris, Jeno ; Nicoletti, Richard ; Gifford, James ; Krieger, Brian ; Jatoi, Aminah. / Growth differentiating factor-15 (GDF-15) : A potential biomarker and therapeutic target for cancer-associated weight loss. In: Oncology Letters. 2016 ; Vol. 12, No. 5. pp. 4219-4223.
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AB - Growth differentiating factor-15 (GDF-15), also known as macrophage inhibiting factor-1, is a member of the transforming growth factor-β superfamily, which has been implicated in cancer-associated weight loss. The present study investigated the association between cancer-associated weight loss and plasma GDF-15 concentration, as well as other biomarkers, in patients with metastatic lung or exocrine pancreatic cancer. A total of 218 patients were enrolled over a 1-year period. The patient cohort included 152 patients with incurable lung cancer and 66 patients with incurable pancreatic cancer. Of the 218 patients, 98 (45%) reported >5% weight loss, 62 (28%) reported ≤5% weight loss and 58 (27%) reported no weight loss in the 6 months prior to diagnosis. In lung cancer patients, higher circulating GDF-15 levels were significantly associated with weight loss; lung cancer patients who reported >5% weight loss (n=56) were found to exhibit twice the circulating concentration of GDF-15 compared with those that exhibited no weight loss (n=48) (P<0.0001). Additional mediators, including Activin A, interleukin (IL)-12, vascular endothelial growth factor A, IL-1 receptor α, eotaxin and platelet derived growth factor-BB, were also associated with weight loss; however, the associations were not as strong. In pancreatic cancer patients, no association between GDF-15 levels and weight loss was identified. However, higher circulating GDF-15 levels were consistently associated with poor survival in univariate [hazard ratio (HR), 1.13; 95% confidence interval (CI), 1.02-1.23; P=0.016] and multivariate [HR, 1.1; 95% CI, 1.02-1.24; P=0.03] analysis, respectively. Thus, GDF-15 requires further study as a biomarker and potential therapeutic target in cancer-associated weight loss, particularly in lung cancer patients.

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