Boldrini Laura, Giordano Mirella, Servadio Adele, Niccoli Cristina, Bertoglio Pietro, Lucchi Marco, Melfi Franca, Mussi Alfredo, Fontanini Gabriella
Department of Surgical, Medical, Molecular Pathology and Critical Care, University of Pisa, I‑56126 Pisa, Italy.
Unit of Thoracic Surgery, Azienda Ospedaliero‑Universitaria Pisana, I‑56126 Pisa, Italy.
Mol Med Rep. 2017 Jun;15(6):3451-3458. doi: 10.3892/mmr.2017.6430. Epub 2017 Apr 3.
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.
非小细胞肺癌（NSCLC）占全球所有肺癌相关死亡人数的约70%。丝氨酸/苏氨酸蛋白激酶肿瘤进展位点2 [TPL2/MAP3激酶8（MAP3K8）] 可能影响致癌事件；然而，TPL2在肺癌发生中的作用仍不清楚。本研究聚焦于TPL2在101例早期NSCLC患者中的潜在预后作用。由于TPL2是miR-21的潜在靶点，因此还检测了TPL2与miR-21表达之间的关联。使用逆转录定量聚合酶链反应（RT-qPCR）对TPL2和miR-21 mRNA表达进行定量。通过免疫组织化学（IHC）评估TPL2蛋白水平。本研究发现，101例中有52例（51%）TPL2的mRNA表达低而49例（49%）高。TPL2蛋白表达的IHC分析结果常与mRNA结果一致。未观察到TPL2的mRNA表达与NSCLC患者的主要临床病理特征之间存在统计学显著关联，也未发现TPL2与miR-21之间存在关联。与预后不良的患者相比，预后良好的NSCLC患者的TPL2 mRNA表达显著更高（无病间期P=0.009；总生存期P=0.024）。关注受影响患者腺癌中TPL2 mRNA表达的差异，与其他亚型相比，贴壁型腺癌中TPL2表达更高（P=0.012）。据我们所知，本研究首次在早期NSCLC中研究了TPL2与miR-21以及不同腺癌亚型的关系。由于其重要的转化意义，未来的研究必须阐明TPL2参与肺癌发生的机制。
