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Folic Acid Phenotype (FAP) Is A Superior Biomarker Predicting Response To Pemetrexed-based Chemotherapy In Malignant Pleural Mesothelioma

F. Mairinger, C. Vollbrecht, E. Flom, D. Christoph, K. Schmid, J. Kollmeier, H. Popper, T. Mairinger, Robert Fred Henry Walter
Published 2017 · Medicine

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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.
This paper references
Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug Response
A. Calascibetta (2010)
Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome
Robert Fred Henry Walter (2016)
Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA levels in tumor tissues and the efficacy of 5-fluorouracil in patients with non-small-cell lung cancer
Y Shintani (2004)
Thymidylate synthase but not excision repair cross-complementation group 1 tumor expression predicts outcome in patients with malignant pleural mesothelioma treated with pemetrexed-based chemotherapy.
L. Righi (2010)
Pemetrexed plus carboplatin in elderly patients with malignant pleural mesothelioma: combined analysis of two phase II trials
G. Ceresoli (2008)
Thymidylate synthase levels as a therapeutic and prognostic predictor in breast cancer.
R. Nishimura (1999)
Prognostic value of thymidylate synthase, Ki-67, and p53 in patients with Dukes' B and C colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project collaborative study.
C. Allegra (2003)
Prognostic value of p53, glutathione S-transferase pi, and thymidylate synthase for neoadjuvant cisplatin-based chemotherapy in head and neck cancer.
H. Shiga (1999)
Chemotherapy for malignant pleural mesothelioma: past results and recent developments.
S. Tomek (2004)
Folylpoly-Glutamate Synthetase Expression Is Associated with Tumor Response and Outcome from Pemetrexed-Based Chemotherapy in Malignant Pleural Mesothelioma
D. Christoph (2012)
Pemetrexed (ALIMTA), A Novel Multitargeted Antineoplastic Agent
A. Adjei (2004)
Review of pemetrexed in combination with cisplatin for the treatment of malignant pleural mesothelioma
Ranjit K Goudar (2008)
Why the need for qPCR publication guidelines?--The case for MIQE.
S. Bustin (2010)
Therapeutic potential of antisense oligodeoxynucleotides to down-regulate thymidylate synthase in mesothelioma
Janet Flynn (2006)
Thymidylate synthase and dihydrofolate reductase expression in non-small cell lung carcinoma: the association with treatment efficacy of pemetrexed.
C. Chen (2011)
Regulation of matrix metalloprotease activity in malignant mesothelioma cell lines by growth factors
Z. Liu (2003)
The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments.
S. Bustin (2009)
Thymidylate synthase as a determinant of 5-fluoro-2'-deoxyuridine response in human colonic tumor cell lines.
S. Berger (1988)
Reduced Folate Carrier and Folylpolyglutamate Synthetase, but not Thymidylate Synthase Predict Survival in Pemetrexed-Treated Patients Suffering from Malignant Pleural Mesothelioma
F. Mairinger (2013)
resistance proteins associated with response and outcome to platinumbased chemotherapy in malignant pleural mesothelioma
S Ting (2013)
Thymidylate Synthase and Excision Repair Cross-Complementing Group-1 as Predictors of Responsiveness in Mesothelioma Patients Treated with Pemetrexed/Carboplatin
P. A. Zucali (2011)
Modified RECIST criteria for assessment of response in malignant pleural mesothelioma.
M. Byrne (2004)
Investigation of the prognostic and predictive value of thymidylate synthase, p53, and Ki-67 in patients with locally advanced colon cancer.
C. Allegra (2002)
Implication of thymidylate synthase in the outcome of patients with invasive ductal carcinoma of the pancreas and efficacy of adjuvant chemotherapy using 5-fluorouracil or its derivatives
M. Takamura (2002)
ERCC1, MLH1, MSH2, MSH6, and βIII-tubulin: resistance proteins associated with response and outcome to platinum-based chemotherapy in malignant pleural mesothelioma.
S. Ting (2013)
ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy.
Y. Shirota (2001)
The efficacy of pemetrexed as a thirdor fourth-line therapy and the significance of thymidylate synthase expression in patients with advanced non-small cell lung cancer
MH Chang (2010)
R: A language and environment for statistical computing.
R. Team (2014)
Prognostic value of thymidylate synthase expression in patients with p-stage I adenocarcinoma of the lung.
T. Nakagawa (2002)
Chemotherapy for malignant pleural mesothelioma: past results and recent developments
S. Tomek (2003)
Significance of thymidylate synthase and thyroid transcription factor 1 expression in patients with nonsquamous non-small cell lung cancer treated with pemetrexed-based chemotherapy.
J. Sun (2011)
FFPE tissue as a feasible source for gene expression analysis--a comparison of three reference genes and one tumor marker.
R. F. Walter (2013)
Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma.
G. Ceresoli (2006)
Induction of resistance to the multitargeted antifolate Pemetrexed (ALIMTA) in WiDr human colon cancer cells is associated with thymidylate synthase overexpression.
J. Sigmond (2003)
The efficacy of pemetrexed as a third- or fourth-line therapy and the significance of thymidylate synthase expression in patients with advanced non-small cell lung cancer.
M. H. Chang (2010)
Low expression of γ-glutamyl hydrolase mRNA in primary colorectal cancer with the CpG island methylator phenotype
K. Kawakami (2008)
Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma
G. Ceresoli (2013)
Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase
P. Ceppi (2006)
Factors predictive of survival among 337 patients with mesothelioma treated between 1984 and 1994 by the Cancer and Leukemia Group B.
J. Herndon (1998)

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