Roh Mee Sook, Lee Ji Hyun, Kang Kyung Woo, Nam Hyun-Yeol, Jung Sang Bong, Kim Kyungeun, Lee Eun Hee, Park Moon-Il, Kim Mee-Seon, Lee Hyoun Wook
Department of Pathology, Dong-A University College of Medicine, Busan, South Korea.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea.
Virchows Arch. 2015 Dec;467(6):667-673. doi: 10.1007/s00428-015-1860-2. Epub 2015 Oct 7.
Phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) binding protein (4E-BP1) results in release of eIF4E, which sequentially relieves translational repression and enhances oncogenic protein synthesis. We assessed the expression of phosphorylated 4E-BP1 (p-4E-BP1) in small-cell lung cancer (SCLC) and its correlation with clinicopathological factors and patient survival. This study included 117 SCLCs, which comprised 108 primary and 9 metastatic tumor tissues. We performed immunohistochemical staining for p-4E-BP1 in 117 tumors and found that 77 (66 %) were positive for p-4E-BP1 with cytoplasmic and/or nuclear immunostaining. The positive rate of p-4E-BP1 staining was significantly higher in never smokers (p = 0.034) and metastatic tumor tissues (p = 0.027). Patients with p-4E-BP1-positive SCLC tended to have poor performance status, although the difference was not statistically significant (p = 0.087). High p-4E-BP1 expression was significantly correlated with worse overall survival (OS) in all cohorts (p = 0.016). After stratification by clinical stage, p-4E-BP1 expression showed a stronger relationship with OS in patients with limited disease (p = 0.008). In addition, when stratified by treatment status, p-4E-BP1 expression was still significantly associated with worse OS in a subgroup of patients who completed treatment (p = 0.021). Our results indicate that p-4E-BP1 expression could represent oncogenic potential and contribute to the progression and aggressiveness of SCLC, suggesting it could be a candidate prognostic biomarker of SCLC, especially in limited disease.
真核生物翻译起始因子4E（eIF4E）结合蛋白（4E-BP1）的磷酸化导致eIF4E释放，进而依次解除翻译抑制并增强致癌蛋白的合成。我们评估了磷酸化4E-BP1（p-4E-BP1）在小细胞肺癌（SCLC）中的表达及其与临床病理因素和患者生存的相关性。本研究纳入了117例SCLC，包括108例原发性肿瘤组织和9例转移瘤组织。我们对117例肿瘤进行了p-4E-BP1的免疫组织化学染色，发现77例（66%）p-4E-BP1呈阳性，免疫染色定位于细胞质和/或细胞核。p-4E-BP1染色的阳性率在从不吸烟者（p = 0.034）和转移瘤组织（p = 0.027）中显著更高。p-4E-BP1阳性的SCLC患者往往表现状态较差，尽管差异无统计学意义（p = 0.087）。在所有队列中，高p-4E-BP1表达与较差的总生存期（OS）显著相关（p = 0.016）。按临床分期分层后，p-4E-BP1表达与局限期患者的OS关系更强（p = 0.008）。此外，按治疗状态分层时，在完成治疗的患者亚组中，p-4E-BP1表达仍与较差的OS显著相关（p = 0.021）。我们的结果表明，p-4E-BP1表达可能代表致癌潜能，并促进SCLC的进展和侵袭性，提示它可能是SCLC的候选预后生物标志物，尤其是在局限期疾病中。
