Folic acid phenotype (FAP) is a superior biomarker predicting response to pemetrexed-based chemotherapy in malignant pleural mesothelioma

Our plain-English summary of Folic acid phenotype (FAP) is a superior biomarker predicting response to pemetrexed-based chemotherapy in malignant pleural mesothelioma, by F.D. Mairinger, C. Vollbrecht, E. Flom, et al (Oncotarget, 2017).

The study

• Authors: F.D. Mairinger, C. Vollbrecht, E. Flom, D.C. Christoph, K.W. Schmid, J. Kollmeier, H.H. Popper, T. Mairinger, R.F.H. Walter
• Journal: Oncotarget
• Published: 2017;8(23):37502-37510
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare tumor linked to a dismal prognosis. Even the most effective chemotherapeutical regime of pemetrexed combined with cisplatin leads to a remission-rate of only about 40%. The reasons for the rather poor efficacy remain largely unknown.

Results: Phenotypes were significantly associated with progression (p=0.0279) and remission (p=0.0262). Cox-regression revealed significant associations between SLC19A1/TYMS-ratio (p=0.0076) as well as FPGS/TYMS-ratio (p=0.0026) and OS. For differentiation by risk-groups, COXPH identified a strong correlation (p=0.0008).

Methods: 56 MPM specimens from patients treated with pemetrexed were used for qPCR analysis. Phenotypes and risk groups were defined by their expression levels of members of the folic acid metabolism and correlated to survival and objective response.

Conclusion: Our results indicate that the balance between folic acid uptake, activation and metabolism plays a crucial role in response to pemetrexed-based chemotherapy and the prognosis of MPM patients. Implementing this marker profile in MPM stratification may help to individualize MPM-therapy more efficiently.

In plain English

This study asked whether the activity of three genes involved in handling folic acid inside tumor cells (SLC19A1, FPGS and TYMS) was linked to how malignant pleural mesothelioma responded to pemetrexed-based chemotherapy. The authors measured gene activity in stored tumor samples from 56 patients from a Berlin hospital biobank. The samples were obtained between 2002 and 2009 and collected before treatment. Tumors were sorted into two 'folic acid phenotype' groupings (FAP1 and FAP2) and into risk groups. Survival analysis included only the 44 patients with epithelioid tumors. FAP1 was significantly associated with progression (p=0.0279) and remission (p=0.0262). FAP2 did not reach statistical significance for remission (p=0.0595). Higher SLC19A1/TYMS and FPGS/TYMS ratios were associated with longer overall survival. Risk groups were associated with survival (p=0.0008). The low-risk group, 17.1% of patients, had a 3-year survival rate of approximately 80%. The authors concluded that the balance between folic acid uptake, activation and use plays a crucial role in treatment response and prognosis. They said the results should be confirmed in larger prospective studies. The study did not address asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory gene expression (qPCR) study of archived tumor samples, linked to recorded chemotherapy response and survival
• Who was studied: Tumor samples from 56 patients with malignant pleural mesothelioma from the biobank of the Department of Pathology, Helios Klinikum Emil von Behring, Berlin, Germany, obtained between 2002 and 2009. Survival analysis was restricted to 44 patients with epithelioid histology.
• Exposure: Pemetrexed-based chemotherapy (at least one cycle), and tumor expression of the SLC19A1, FPGS and TYMS genes. Asbestos exposure was not studied.
• Main results:
  • The folic acid phenotype FAP1 was significantly associated with objective tumor response: progression (p=0.0279) and remission (p=0.0262) under pemetrexed-based chemotherapy.
  • FAP2 did not reach statistical significance when correlated with remission (p=0.0595).
  • In Cox regression, high SLC19A1/TYMS ratios were associated with prolonged overall survival (p=0.0076, HR: 1.48), and high FPGS/TYMS ratios were associated with prolonged overall survival (p=0.0026, HR: 2.18).
  • Risk groups were associated with overall survival (p=0.0008, HR: 5.34), but only the low-risk group showed prolonged survival.
  • The low-risk group made up 17.1% of the patients studied. It had a 3-year survival rate of approximately 80% and a five-year survival rate of more than 40%. Tumors in this group did not show progression.
• The authors' conclusion: The authors concluded that the balance between folic acid uptake, activation and utilization plays a crucial role in response to pemetrexed-based chemotherapy and in prognosis in malignant pleural mesothelioma.
• Limitations the authors state:
  • The authors stated that the phenotypes and risk groups need to be validated in larger prospective studies to confirm the results.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Biomarker, Pemetrexed (Alimta), Chemotherapy, Pleural Mesothelioma, Prognosis, Cisplatin.

Related studies

• Folylpoly-glutamate synthetase expression is associated with tumor response and outcome from pemetrexed-based chemotherapy in malignant pleural mesothelioma — D.C. Christoph, B.R. Asuncion, et al. (2012)
• Reduced folate carrier and folylpolyglutamate synthetase, but not thymidylate synthase predict survival in pemetrexed-treated patients suffering from malignant pleural mesothelioma — F. Mairinger, C. Vollbrecht, et al. (2013)
• Thymidylate synthase and folyl-polyglutamate synthase are not clinically useful markers of response to pemetrexed in patients with malignant pleural mesothelioma — D.E. Lustgarten, C. Deshpande, et al. (2013)
• The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication — C.E. Hooper, I.D. Lyburn, et al. (2015)
• The issue of studies evaluating biomarkers which predict outcome after pemetrexed-based chemotherapy in malignant pleural mesothelioma — F. Mairinger, C. Vollbrecht, et al. (2013)
• Metabolic response assessment with 18F-FDG-PET/CT is superior to modified RECIST for the evaluation of response to platinum-based doublet chemotherapy in malignant pleural mesothelioma — S. Kanemura, K. Kuribayashi, et al. (2017)

Browse more research in Oncotarget, or return to medical research.