Increased phosphorylation of 4 E ‐ binding protein 1 predicts poor prognosis for patients with colorectal cancer

As demonstrated in previous studies, the phosphorylated form of 4E-binding protein 1 (p-4E-BP1) may be a suitable tumor biomarker. The aim of the current study was to examine the expression status of p-4E-BP1 in colorectal cancer (CRC), in order to determine its clinical significance. The present study enrolled 89 patients with CRC that had undergone radical resection. Paired tumor and adjacent normal tissues were evaluated using immunohistochemistry to detect the protein expression of p-4E-BP1 and phosphatase and tensin homolog (PTEN). The study identified 53 cases (59.6%) that exhibited moderate or high expression of p-4E-BP1 in tumor tissues, compared with little or no expression in the adjacent normal tissues. Conversely, PTEN protein expression was markedly lower in CRC compared with adjacent normal tissues. p-4E-BP1 protein upregulation tissues samples was consistent with PTEN downregulation in CRC samples. p-4E-BP1 overexpression was predominant in patients with metastasis to the regional lymph nodes. Moderate/high expression of p-4E‐BP1 protein was significantly associated with adverse overall survival (OS) in patients. Statistical analysis using the Cox proportional hazards model, indicated that p-4E-BP1 expression was an independent factor suitable for predicting OS in CRC patients, which was independent of lymph node metastasis. In conclusion, p-4E-BP1 protein expression appears to be upregulated in CRC, suggesting that it may be a suitable biomarker for predicting CRC prognosis. Introduction Colorectal cancer (CRC) is a commonly occurring cancer, with approximately one million new cases diagnosed annually worldwide (1). In its early stages, the disease is curable with surgery, however 50‐60% of patients diagnosed with CRC will develop metastases (2). In order to facilitate the development of more effective treatments for patients with CRC, prognostic and predictive markers need to be identified. Currently, tumor staging at the time of diagnosis and determination of histological grade, such as the tumor node metastasis (TNM) and the Duke's staging systems, are the two most important techniques. Previous studies have identified several biomarkers in multiple tumor types that are associated with disease progression and clinical outcome. Among these established biomarkers, 4E-binding protein 1 (4E-BP1) is associated with cell signaling and downstream regulation of the mitogen-activated protein kinase (MAPK) signaling pathway and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway (3). 4E-BP1 is activated when phosphorylated by AKT and ribosomal protein S6 kinase B1, and serves a critical role in RNA translation and in the regulation of cell growth (4,5). Previous studies have established that phosphorylated 4E-BP1 (p-4E-BP1) is involved in the initiation and progression of cancer. Therefore, p-4E-BP1 may be a suitable tumor biomarker. Certain types of tumor, including those of the esophagus, stomach, breast, ovary, uterine cervix and endometrium exhibit high expression levels of p-4E-BP1, which has been demonstrated to be associated with poor prognosis (6-11). However, the prognostic value of p-4E-BP1 in CRC remains unclear. The aim of the present study was to assess the status of p-4E-BP1 in CRC specimens, and to establish its clinical significance. As phosphatase and tensin homolog (PTEN) is an important member of the PI3K/AKT signaling pathway, the association between p-4E-BP1 and PTEN expression was also examined. Materials and methods Study population. The present study enrolled 89 patients (48 men, 41 women; age range, 40-81 years; median age, Increased phosphorylation of 4E‐binding protein 1 predicts poor prognosis for patients with colorectal cancer YUFENG MIAO1,2, LIGE CHEN3, CUIFEN SHI4, RENGEN FAN5, PING CHEN2, HONGQI LIU2, AIHUA XIA6 and HAIXIN QIAN1 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006; Departments of 2Medical Oncology and 3Pharmacy, Yancheng First People's Hospital, Yancheng, Jiangsu 224001; 4Department of Hepatology, Yancheng No. 2 People's Hospital, Yancheng, Jiangsu 224002; Departments of 5General Surgery and 6Clinical Laboratory, Yancheng First People's Hospital, Yancheng, Jiangsu 224001, P.R. China Received November 11, 2015; Accepted December 23, 2016 DOI: 10.3892/mmr.2017. 6352 Correspondence to: Professor Haixin Qian, Department of General Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, Jiangsu 215006, P.R. China E-mail: haixinqian@tom.com