Activin-A, Growth Differentiation Factor-11 and Transforming Growth Factor-β as predictive biomarkers for platinum chemotherapy in advanced non-small cell lung cancer

Jennifer Lim; Alexander Murphy; Stephen Wong; Adnan Nagrial; Deme Karikios; Dariush Daneshvar; Rachael McCloy; Angela M Steinmann; Sandra O'Toole; Venessa Chin

doi:10.1016/j.ctarc.2022.100576

Activin-A, Growth Differentiation Factor-11 and Transforming Growth Factor-β as predictive biomarkers for platinum chemotherapy in advanced non-small cell lung cancer

Cancer Treat Res Commun. 2022:32:100576. doi: 10.1016/j.ctarc.2022.100576. Epub 2022 May 13.

Authors

Affiliations

¹ The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, Australia; The University of New South Wales, Sydney, Australia; St Vincent's Hospital, 390 Victoria Street Darlinghurst, Sydney, Australia. Electronic address: j.lim@garvan.org.au.
² The Crown Princess Mary Cancer Centre, 166-174 Hawkesbury Road, Westmead Sydney, Australia; Westmead Hospital, Cnr Hawkesbury Road and Darcy Road, Westmead, Sydney, Australia. Electronic address: alexander.murphy@health.nsw.gov.au.
³ The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, Australia; St Vincent's Hospital, 390 Victoria Street Darlinghurst, Sydney, Australia. Electronic address: Stephen.wong4@svha.org.au.
⁴ The Crown Princess Mary Cancer Centre, 166-174 Hawkesbury Road, Westmead Sydney, Australia; Westmead Hospital, Cnr Hawkesbury Road and Darcy Road, Westmead, Sydney, Australia. Electronic address: adnan.nagrial@health.nsw.gov.au.
⁵ Nepean Cancer and Wellness Centre, Somerset Street, Kingswood, Sydney, Australia; Nepean Clinical School, Sydney Medical School, 62 Derby Street, Kingswood, University of Sydney, Sydney, Australia. Electronic address: deme.karikios@health.nsw.gov.au.
⁶ Westmead Hospital, Cnr Hawkesbury Road and Darcy Road, Westmead, Sydney, Australia. Electronic address: dariush.daneshvar@health.nsw.gov.au.
⁷ The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, Australia. Electronic address: r.zekanovic@garvan.org.au.
⁸ The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, Australia. Electronic address: angela.murphy6@health.nsw.gov.au.
⁹ The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, Australia. Electronic address: s.otoole@garvan.org.au.
¹⁰ The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, Australia; The University of New South Wales, Sydney, Australia; St Vincent's Hospital, 390 Victoria Street Darlinghurst, Sydney, Australia. Electronic address: v.chin@garvan.org.au.

PMID: 35597155
DOI: 10.1016/j.ctarc.2022.100576

Abstract

Background: Despite advances in immunotherapy and targeted therapy, platinum-based chemotherapy remains crucial for many patients with advanced non-small cell lung cancer (NSCLC). Resistance to platinum chemotherapy is common, and predictive biomarkers are needed to tailor treatment to patients likely to respond. In vitro evidence implicates the transforming growth factor-β (TGF-β) superfamily ligands activin-A and growth differentiation factor 11 (GDF-11) in innate platinum resistance. We performed a validation study to assess their utility as predictive biomarkers of platinum chemotherapy response in advanced NSCLC.

Patients and methods: Our study included 123 adult patients with advanced NSCLC without a driver mutation treated with platinum chemotherapy. 98 patients were from a retrospective cohort and 25 from a prospective cohort. We performed immunohistochemistry staining for Activin-A, GDF-11 and TGF-β on tumour samples for each patient and analysed IHC expression with objective radiological response and overall survival.

Results: The overall median survival was 14.8 months. We performed statistical analysis around a cytoplasmic score of 8/18 for Activin-A and GDF-11 based on previously published work, and 110/30 for TGF-β based on a calculated cutpoint for significance. No survival difference was detected between these groups for Activin-A (p=0.35), GDF-11 (p=0.57) or TGF-β (p=0.34). There was no association between rates of progressive disease and high Activin-A expression (p=0.43), high GDF-11 expression (p=1.0) or high TGF-β expression p=0.89).

Conclusion: Within the confines of our study, Activin-A, GDF-11 and TGF-β expression was not a predictor of objective radiological response to chemotherapy or overall survival.

Keywords: Activin-A; Non-small cell lung cancer; TGF-β; biomarkers; immunohistochemistry; platinum chemotherapy.

MeSH terms

Activins / metabolism
Activins / therapeutic use
Adult
Biomarkers
Bone Morphogenetic Proteins
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / pathology
Growth Differentiation Factors / therapeutic use
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / pathology
Organoplatinum Compounds* / therapeutic use
Platinum / therapeutic use
Prospective Studies
Retrospective Studies
Transforming Growth Factor beta / metabolism
Transforming Growth Factor beta / therapeutic use
Transforming Growth Factors / therapeutic use

Substances

Biomarkers
Bone Morphogenetic Proteins
GDF11 protein, human
Growth Differentiation Factors
Organoplatinum Compounds
Transforming Growth Factor beta
activin A
Activins
Platinum
Transforming Growth Factors