title: Prognostic role of TPL2 in early‑stage non‑small cell lung cancer.
abstract: Non‑small cell lung cancer (NSCLC) accounts for ~70% of all lung cancer‑associated mortalities worldwide. The serine/threonine protein kinase tumor progression locus 2 [TPL2/MAP3 kinase 8 (MAP3K8)] may impact oncogenic events; however the role of TPL2 in lung carcinogenesis remains unclear. The present study was focused on the potential prognostic role of TPL2 in 101 patients with early‑stage NSCLC. Since TPL2 is a potential target of miR‑21, the association between TPL2 and miR‑21 expression was also examined. TPL2 and miR‑21 mRNA expression was quantified using reverse transcription quantitative polymerase chain reaction (RT‑qPCR). TPL2 protein levels were evaluated by immunohistochemistry (IHC). The present study identified that the mRNA expression of TPL2 was low in 52/101 (51%) cases and high in 49/101 (49%) cases. IHC analysis of TPL2 protein expression often demonstrated identical mRNA results. No statistically significant associations were observed between the mRNA expression of TPL2 and the predominant clinicopathological characteristics of the patients with NSCLC, as well as identifying no association between TPL2 and miR‑21. TPL2 mRNA expression was significantly higher in patients with NSCLC with good prognosis (disease‑free interval P=0.009; overall survival P=0.024), when compared with those of poor prognosis. Focusing on the difference in mRNA expression of TPL2 among the adenocarcinomas in affected patients, TPL2 was more highly expressed in lepidic adenocarcinomas compared with in the other subtypes (P=0.012). The present study is the first examination, to the best of our knowledge, of TPL2 in early‑stage NSCLC in relation to miR‑21, and in different adenocarcinoma subtypes. Future studies must clarify the mechanism by which TPL2 is involved in lung carcinogenesis due to its important translational implications.
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Care, University of Pisa, I‑56126 Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Boldrini
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Care, University of Pisa, I‑56126 Pisa, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Giordano
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Care, University of Pisa, I‑56126 Pisa, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Servadio
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Care, University of Pisa, I‑56126 Pisa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Niccoli
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Care, University of Pisa, I‑56126 Pisa, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Bertoglio
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Care, University of Pisa, I‑56126 Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lucchi
authors.affiliation: Unit of Thoracic Surgery, Azienda Ospedaliero‑Universitaria Pisana, I‑56126 Pisa, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Melfi
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Care, University of Pisa, I‑56126 Pisa, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mussi
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Care, University of Pisa, I‑56126 Pisa, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fontanini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D020930:MAP Kinase Kinase Kinases / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
chemical_list: D014408:Biomarkers, Tumor; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human