title: The combination of strong immunohistochemical mtTFA expression and a high survivin index predicts a shorter disease-specific survival in pancreatic ductal adenocarcinoma.
abstract: Mitochondrial transcription factor A (mtTFA) plays a crucial role in both the transcription and maintenance of mitochondrial DNA. A high expression of mtTFA has been demonstrated in several solid tumors, and is closely associated with cancer cell survival/apoptosis and growth. However, its expression pattern in pancreatic ductal adenocarcinoma (PAC) remains to be elucidated. Additionally, our groups have recently revealed that a subset of apoptosis-related genes is strongly regulated by mtTFA, and that two putative mtTFA binding sites are present in the promoter region of the survivin gene, which is a member of the inhibitor-of-apoptosis protein family. We therefore investigated the correlation of the immunohistochemical mtTFA expression and the survivin index with various clinicopathological variables and the prognosis, using 70 paraffin-embedded tumor samples from patients with surgically-resected PAC. The mtTFA expression or survivin index was considered to be strong or high when ≥30% or 10% of the PAC cells showed positive staining, respectively. Strong mtTFA expression and/or a high survivin index was revealed to have a significant relationship to a pathologically high tumor grading and advanced tumor stage. Moreover, mtTFA showed significantly high co-expression with survivin. Univariate and multivariate analyses demonstrated that both the strong mtTFA expression and high survivin index groups had significantly shorter survival rates, especially within the first two years postoperatively. The combination of strong mtTFA expression and a high survivin index may predict a poor prognosis in patients with PAC, and these new biomarkers might offer useful information for the early clinical management.
authors.affiliation: Department of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Departments of Pathology and Cell Biology, and Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Kitada
authors.affiliation: Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Uramoto
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan, and Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhi
authors.affiliation: Department of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kawatsu
authors.affiliation: Department of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Takeda
authors.affiliation: Department of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Seichi
authors.initials: S
authors.lastname: Horie
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nabeshima
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Noguchi
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, and Laboratory of Pathology, Fukuoka Wajiro Hospital, Fukuoka, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
authors.affiliation: Department of Occupational Pneumology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.affiliation: The President Laboratory, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. sousuke@med.uoeh-u.ac.jp.
authors.forename: Sohsuke
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D000077022:Survivin; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D024101:Mitochondrial Proteins; D000077022:Survivin; D014157:Transcription Factors; C422562:mitochondrial transcription factor A