J Cancer 2017; 8(18):3755-3763. doi:10.7150/jca.20828 This issue Cite
Research Paper
1. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China;
2. Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China;
3. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China;
4. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China;
5. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China;
6. Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China;
7. Radiotherapy and Chemotherapy Department, the 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
*Weiwei Yu and Li Chu contributed equally to this work.
Background: The AKT signalling pathway controls survival and growth in many malignant tumours. However, the prognostic value of phosphorylated AKT1 (p-AKT1) for locoregional-progression free survival (LPFS) in oesophageal squamous cell carcinoma (ESCC) has not been established. Our aim was to develop a nomogram to predict local recurrence using p-AKT1 and main clinical characteristics in patients with thoracic ESCC undergoing radical three-field lymph node dissection.
Methods: Immunohistochemistry was performed to examine p-AKT1 expression in 181 thoracic ESCC patients. The Kaplan-Meier method was used to calculate LPFS. Cox regression analysis was also performed to evaluate prognostic factors. A nomogram comprising biological and clinical factors was established to predict LPFS.
Results: The 5-year LPFS rate was 63.9%. Multivariate analysis revealed that expression of p-AKT1 (p<0.001), pathologic N category (p=0.004) and number of lymph nodes retrieved (p=0.001) were independent prognostic factors for LPFS. Increased expression of p-AKT1 was associated with decreased LPFS in patients with ESCC. In addition, a nomogram was established based on all significant independent factors for locoregional recurrence risk. Harrell's c-index for predicting LPFS was 0.78.
Conclusion: Activation of AKT1 was associated with poor locoregional control in ESCC patients. The nomogram, based on p-AKT1 expression and clinically significant parameters, could be used as an accurate stratification model for predicting locoregional recurrence in patients with ESCC after radical resection.
Keywords: Esophageal squamous cell carcinoma, Locoregional-progression free survival, Phosphorylated AKT1, Nomogram, Prognostic factor