title: Acyl-CoA thioesterase 8 is a specific protein related to nodal metastasis and prognosis of lung adenocarcinoma.
abstract: Metastasis is a major cause of cancer recurrence or death. This study attempted to quantitatively identify different proteins in metastatic lung adenocarcinoma. The N/T quotient [number of metastatic lymph nodes (n)/tumor diameter (cm)] was used to select samples with an extreme metastatic phenotype. Among the six fresh frozen lung adenocarcinoma specimens, the three showing the highest N/T quotient represented the metastatic group, and others with the greatest tumor diameters without metastasis represented the non-metastatic group. After 2-dimensional electrophoresis, the significantly different protein spots were selected by image analysis and analyzed with MALDI-TOF mass spectrometry. Acyl-CoA thioesterase 8 isoform c (ACOT8) was one of most overexpressed proteins in the metastatic group, and it was validated by Western blot and immunohistochemical staining on 108 paraffin-embedded tumor samples. High ACOT8 expression was correlated with lymph node metastasis (p=0.002), recurrence (p=0.034), predominant histologic subtypes (p=0.007), and higher stage (p=0.005). In multivariate analysis, high ACOT8 expression was significantly associated with increased risks of lymph node metastasis (p=0.009) and cancer-related death (p=0.030), independent of clinical factors. ACOT8 may be a candidate prognostic biomarker and therapeutic target of lung adenocarcinoma.
authors.affiliation: Department of Pathology, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Woon Yong
authors.initials: WY
authors.lastname: Jung
authors.forename: Young Hye
authors.initials: YH
authors.lastname: Kim
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Ryu
authors.forename: Baek-Hui
authors.initials: BH
authors.lastname: Kim
authors.forename: Bong Kyung
authors.initials: BK
authors.lastname: Shin
authors.forename: Aeree
authors.initials: A
authors.lastname: Kim
authors.forename: Han Kyeom
authors.initials: HK
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000401:mortality / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005260:Female; D005629:Frozen Sections; D006801:Humans; D007091:Image Processing, Computer-Assisted; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010170:Palmitoyl-CoA Hydrolase / Q000378:metabolism*; D056910:Republic of Korea / Q000453:epidemiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C106353:ACOT8 protein, human; D010170:Palmitoyl-CoA Hydrolase