title: Thyroid transcription factor 1 expression is associated with outcome of patients with non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy.
abstract: Pemetrexed is an antifolate cytostatic agent targeting several folate-dependent enzymatic pathways, widely used in the treatment of locally advanced or metastatic stage non-small cell lung cancer. Aside from the non-squamous histology, there is still no available molecular biomarker predicting treatment efficacy of pemetrexed-based chemotherapy. The aim of our retrospective study was to evaluate the association of thyroid transcription factor 1 expression with outcome of a large cohort of patients with non-squamous non-small cell lung cancer treated with pemetrexed. We retrospectively analysed clinical data of 463 patients with advanced-stage non-small cell lung cancer (IIIB or IV) treated with pemetrexed-based chemotherapy. Thyroid transcription factor 1 expression was assessed using indirect immunohistochemical detection in formalin-fixed paraffin-embedded tumour tissue at the time of diagnosis. Thyroid transcription factor 1 expression was detected in the tumour tissue from 76.0% of patients, and tumours from 24.0% of patients were thyroid transcription factor 1 negative. The median progression-free survival and overall survival for patients with thyroid transcription factor 1 positive tumours were 4.8 and 11.8 months compared to 2.8 and 8.3 months for those with thyroid transcription factor 1 negative tumours (p = 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that thyroid transcription factor 1 expression was significantly associated with progression-free survival (hazard ratio = 1.57, p < 0.001) and also with overall survival (hazard ratio = 1.73, p < 0.001). In conclusion, the results of the conducted retrospective study suggest that the thyroid transcription factor 1 expression was independently associated with progression-free survival and overall survival in patients with advanced-stage non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy.
authors.affiliation: 1 Department of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.|2 Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Fiala
authors.affiliation: 3 Department of Pneumology and Phthisiology, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.
authors.forename: Milos
authors.initials: M
authors.lastname: Pesek
authors.affiliation: 4 Department of Respiratory Diseases and TB, Masaryk University Medical School and Teaching Hospital, Brno, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Skrickova
authors.affiliation: 5 Department of Pneumology and Tuberculosis, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic.
authors.forename: Vitezslav
authors.initials: V
authors.lastname: Kolek
authors.affiliation: 6 Department of Pneumology, Charles University Medical School and Teaching Hospital, Hradec Kralove, Czech Republic.
authors.forename: Frantisek
authors.initials: F
authors.lastname: Salajka
authors.affiliation: 4 Department of Respiratory Diseases and TB, Masaryk University Medical School and Teaching Hospital, Brno, Czech Republic.
authors.forename: Marcela
authors.initials: M
authors.lastname: Tomiskova
authors.affiliation: 4 Department of Respiratory Diseases and TB, Masaryk University Medical School and Teaching Hospital, Brno, Czech Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Satankova
authors.affiliation: 5 Department of Pneumology and Tuberculosis, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic.
authors.forename: Juraj
authors.initials: J
authors.lastname: Kultan
authors.affiliation: 5 Department of Pneumology and Tuberculosis, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Kuliskova
authors.affiliation: 2 Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Svaton
authors.affiliation: 6 Department of Pneumology, Charles University Medical School and Teaching Hospital, Hradec Kralove, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Hrnciarik
authors.affiliation: 7 Institute of Biostatistics and Analysis, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Hejduk
authors.affiliation: 7 Institute of Biostatistics and Analysis, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Chloupkova
authors.affiliation: 8 Department of Nuclear Medicine, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Topolcan
authors.affiliation: 9 The Fingerland Department of Pathology, Charles University Medical Faculty and University Hospital, Hradec Kralove, Czech Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Hornychova
authors.affiliation: 9 The Fingerland Department of Pathology, Charles University Medical Faculty and University Hospital, Hradec Kralove, Czech Republic.
authors.forename: Marketa
authors.initials: M
authors.lastname: Nova
authors.affiliation: 9 The Fingerland Department of Pathology, Charles University Medical Faculty and University Hospital, Hradec Kralove, Czech Republic.
authors.forename: Ales
authors.initials: A
authors.lastname: Ryska
authors.affiliation: 1 Department of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.
authors.forename: Jindrich
authors.initials: J
authors.lastname: Finek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D014157:Transcription Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C504003:TTF1 protein, human; D014157:Transcription Factors; D000068437:Pemetrexed
keywords: Thyroid transcription factor 1; biomarker; expression; non-small cell lung cancer; prognosis; survival