ABSTRACT
Background: Whether all cT3 low rectal cancer patients should receive neoadjuvant chemoradiotherapy (nCRT) remains controversial. The depth of invasion beyond the muscularis propria of the cT3 rectal cancer is of great significance to the selection of a treatment plan and the evaluation of prognosis. Methods: A retrospective analysis was conducted of 187 patients with stage cT3 low rectal cancer, who had been treated at the Department of Colorectal Surgery, The First Affiliated Hospital of Xiamen University from June 2010 to December 2012. The patients were divided into the nCRT group (88 cases) and no-nCRT group (99 cases). Possible significant prognostic factors [i.e., primary tumor volume (PTV), cell differentiation, circumferential resection margin (CRM), nCRT, age, sex, carcinoembryonic antigen (CEA), lymph node status, surgical procedure, etc.] were collected for estimation of disease-free survival (DFS), distant metastases rate (DM), local recurrence rate (LR). Independent predictive factors or survival were determined using Cox proportional hazards model. Results: The mean PTV was 16.2±11.1 (2.07-72.68) cm3. In the univariate and multivariate analyses: nCRT hazards ratio (HR) =4.258, 95% confidence interval (CI): 1.912-9.483 (P<0.001); PTV HR =0.381, 95% CI: 0.181-0.804 (P=0.011); CRM HR =0.227, 95% CI: 0.097-0.532 (P=0.001). For the PTV ≤15 cm3 group, there were no significant differences between the nCRT and no-nCRT group in 3-year follow-up (P>0.05). For the PTV >15 cm3 group, there were significant differences between the nCRT and no-nCRT group in 3-year DFS (84.2% vs. 51.1%; P=0.001), DM (13.1% vs. 31.2%; P=0.017) and LR (2.9% vs. 26.6%; P=0.009). For the CRM negative group, there were significant differences between the nCRT and no-nCRT group in 3-year DFS (94.0% vs. 79.0%; P=0.008), LR (1.5% vs. 10.7%; P=0.028) and DM (4.5% vs. 13.5%; P=0.039). Conclusions: For stage cT3 low rectal cancer patients, nCRT, PTV, and CRM were independent prognostic factors. NCRT may improve the survival of PTV >15 cm3 patients, but may not have a significant effect on patient with PTV ≤15 cm3 and CRM negative. Direct surgery is recommended for this group of patients.
ABSTRACT
The WW domain is composed of 38 to 40 semi-conserved amino acids shared with structural, regulatory, and signaling proteins. WW domain-binding protein 2 (WBP2), as a binding partner of WW domain protein, interacts with several WW-domain-containing proteins, such as Yes kinase-associated protein (Yap), paired box gene 8 (Pax8), WW-domain-containing transcription regulator protein 1 (TAZ), and WW-domain-containing oxidoreductase (WWOX) through its PPxY motifs within C-terminal region, and further triggers the downstream signaling pathway in vitro and in vivo. Studies have confirmed that phosphorylated form of WBP2 can move into nuclei and activate the transcription of estrogen receptor (ER) and progesterone receptor (PR), whose expression were the indicators of breast cancer development, indicating that WBP2 may participate in the progression of breast cancer. Both overexpression of WBP2 and activation of tyrosine phosphorylation upregulate the signal cascades in the cross-regulation of the Wnt and ER signaling pathways in breast cancer. Following the binding of WBP2 to the WW domain region of TAZ which can accelerate migration, invasion and is required for the transformed phenotypes of breast cancer cells, the transformation of epithelial to mesenchymal of MCF10A is activated, suggesting that WBP2 is a key player in regulating cell migration. When WBP2 binds with WWOX, a tumor suppressor, ER transactivation and tumor growth can be suppressed. Thus, WBP2 may serve as a molecular on/off switch that controls the crosstalk between E2, WWOX, Wnt, TAZ, and other oncogenic signaling pathways. This review interprets the relationship between WBP2 and breast cancer, and provides comprehensive views about the function of WBP2 in the regulation of the pathogenesis of breast cancer and endocrine therapy in breast cancer treatment.
