OBJECTIVETo investigate the predictive value of P53, Ki-67, HER2 protein detection in neoadjuvant chemotherapy for adenocarcinoma of gastroesophageal junction (AGEJ).

METHODSPreoperative biopsy specimens and clinical data of 72 patients of locally advanced Siewert II AGEJ between June 2010 and December 2013 were reviewed. All the patients received SOX scheme neoadjuvant chemotherapy, and were divided into effective group (complete response plus partial response) and ineffective group (stable disease plus progressive disease). Expressions of above 3 proteins were detected by immunohistochemistry in all the patients before neoadjuvant chemotherapy. The relationship between various proteins and efficacy of chemotherapy was analyzed by univariate and logistic multivariate regression analyses.

RESULTSAll the 72 patients successfully completed 2 cycles of SOX neoadjuvant chemotherapy, among them, 5 cases (6.9%) with complete response, 30 cases (41.7%) with partial response, 31 cases (43.1%) with stable disease, 6 cases (8.3%) with progressive disease, including 35 cases in effective group and 37 cases in ineffective group. Compared with ineffective group, the positive expression rate of P53 was significantly reduced (25.0% vs. 45.9%, P=0.020), and that of Ki-67 significantly increased (77.1% vs. 43.2%, P=0.003), however, there was no significant difference in the expression rate of HER2 between the two groups (P>0.05). Multivariate analysis showed that Ki-67 was the independent predictive factor for the efficacy of neoadjuvant chemotherapy (P=0.015). Spearman rank correlation showed that Ki-67 expression was positively correlated with HER2 expression (r=0.259, P=0.028), but P53 expression was not correlated with Ki-67 or HER2 (r=0.140, 0.042, P=0.240, 0.725, respectively).

CONCLUSIONSSOX neoadjuvant chemotherapy is safe and effective for AGEJ, especially for patients with depressed expression of P53 and elevated expression of Ki-67, which both may be used as reference for the prediction of chemotherapy efficacy. There is no correlation between P53 and Ki67 proteins, so combined detection may improve the predictive value.

Adenocarcinoma ; diagnosis ; drug therapy ; Esophageal Neoplasms ; diagnosis ; drug therapy ; Esophagogastric Junction ; pathology ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Neoadjuvant Therapy ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Tumor Suppressor Protein p53 ; metabolism

Objective To investigate the effect of long non-coding RNA HOX transcript antisense RNA ( lncRNA HOTAIR ) on the cell proliferation, radiosensitivity and apoptosis of the rectal adenocarcinoma cell lines SW480 and HCT116 in vitro. Methods The expression levels of lncRNA HOTAIR in the rectal adenocarcinoma cell lines ( SW480 and HCT116 ) were assessed by real-time quantitative PCR (RT-qPCR).Silencing of HOTAIR by RNA interference was performed to explore its roles in cell proliferation,radiosensitivity and apoptosis. After treatment with irradiation at a gradient dose,the cell viability was measured and the rate of cell apoptosis was tested. Results Compared with the human rectal epithelial cell lines,the expression of lncRNA HOTAIR was significantly higher in the rectal adenocarcinoma cell lines. The colonic assay demonstrated that the sensitizing enhancement ratios ( SERs) were 1. 58 and 1. 33 for the cells transfected with HOTAIR siRNA in SW480 and HCT116 cell line compared with the control isRNA transfection group. In vitro silencing of lncRNA HOTAIR could enhance the apotosis rate and radiosensitivity of the rectal adenocarcinoma cell line SW480. Conclusion The expression level of lncRNA HOTAIR is correlated with the cellular radiosensitivity, which is probably a parameter for predicting the radiosensitivity of rectal adenocarcinoma cells. Radiotherapy combined with HOTAIR-siRNA can significantly inhibit the cell proliferation,induce cell apoptosis and enhance the radiosensitivity.

Objective To evaluate T lymphocyte changes in esophagogastric junction adenocarcinoma (AEGJ) patients receiving early hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) after radical resection.Methods 98 AEGJ cases were randomized into postoperative early paclitaxel HIPEC group (50 cases) and surgery only group (48 cases).The changes in TLC,CD3 +,CD4 +,CD8 + and CD4 + CD25 + were examined by using flow cytometry on the preoperaive d1,and on the postoperative d 9.Results There were significant differences in cellular ratios of TLC,CD3 +,CD4 +,CD8 + and CD4 + CD25 + between the two groups on postoperative d 9 [(1.85 ± 0.36) × 109/L,(1.28 ± 0.28) ×109/L,t=8.727,P＜0.001;76％ ±6％,65％ ±6％,t =8.680,P＜0.001;57％ ±8％,41％ ± 7％,t =10.246,P ＜0.001:20％ ±7％,25％ ±6％,t =4.037,P ＜0.001;4.2％ ±1.8％;6.7％ ± 2.0％,t =6.548,P ＜ 0.001].Conclusion Postoperative early HIPEC using paclitaxel improves the celluar immune activity of T cell subsets in advanced AEGJ patients.

Objective To evaluate the changes of CEA,CA19-9,CA72-4 of patients with advanced adenocarcinoma of the esophagogastric junction (AEGJ) who received ultra-early precise hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) with paclitaxel (PTX) after radical surgery.Methods From Jul 2014 to Dec 2015 postoperative advanced AEGJ patients were divided to receive ultraearly precise HIPEC (87 cases,HIPEC group) and conventional therapy group (85 cases) in early stage after radical surgery.Serum levels of CEA,CA19-9 and CA72-4 were examined on preoperative day 1 and postoperative day 9.Results On post-op day 9,the level of CEA,CA19-9 and CA72-4 was (2.8 ± 1.3)ng/ml,(22 ±8)IU/ml,(4.1 ± 1.9)IU/ml in HIPEC group,while that was (3.4 ± 1.2)ng/ml,(25 ±11) IU/ml,(4.8 ± 2.1) IU/ml in control group respectively (t =2.453,P =0.015;t =2.241,P =0.026;t =2.154,P =0.033).Conclusion Ultra-early PTX-based HIPEC with advanced AEGJ after radical surgery lowers serum tumor makers of CEA,CA19-9,CA72-4,reducing body's tumor burden.

Objective To explore the expression of heat shock protein (HSP) 105b in advanced adenocarcinoma of esophagogastric junction (AEG) patients and its relation with clinicopathological characteristics and effect of hyperthermic intraperitoneal chemotherapy (HIPEC). Methods We randomly divided 166 cases of advanced AEG who underwent open radical gastrectomy and lymphadenectomy D2 compartment into treatment group (prophylactic HIPEC of paclitaxel after operation) and control group (conventional treatment). Immunohistochemistry was used to detect HSP105b expression in postoperative tumor tissues, and to analyze its relation with clinicopathological characteristics and effect of HIPEC. Results The expression of HSP105b was only associated with tumor vein infiltration (t=4.002, P=0.045). The 3-year disease-free survival rate of the patients with high HSP105b expression was significantly lower than those with low HSP105b expression (56.5% vs. 64.8%, χ²=35.508, P < 0.001), and the disease-free survival rate of the patients with high HSP105b expression in treatment group was significantly lower than that with low HSP105b expression (60.7% vs. 71.5%, χ²=77.459, P < 0.001). Conclusion HSP105b can be used as a prognostic factor and its expression can predict the efficacy of HIPEC in the patients with advanced AEG.

Objective:To study the expression and significance of long noncoding RNA (lncRNA) LINC00657 in diffuse-type adenocarcinoma of esophagogastric junction (AEG).Methods:RT-PCR was used to determine the expression of LINC00657 in AEG tissues and AEG patient-derived tumor cells (PDCs). The expression of E-cadherin in AEG tissues and PDCs was detected. The Kaplan-Meier method was used to evaluate the correlation of LINC00657 expression with the overall survival (OS) of patients.Results:LINC00657 was highly expressed in AEG tissues [(1.41±0.12) vs. (0.61±0.11), t=276.038, P<0.01] and PDCs, while E-cadherin was significantly down-regulated. The expression of LINC00657 was retated to tumor diamer, invassion depth, lymph node metastasis, TNM staging (all P<0.05) In Kaplan-Meier analysis, high levels of LINC00657 were associated with poor prognosis for patients with diffuse-type AEG. In addition, a significant inverse relationship was observed between LINC00657 and E-cadherin expression ( r=-0.529, P<0.001). Conclusions:Elevated expression of LINC00657 in diffuse-type AEG tissues is associated with poor prognosis and may confer a malignant phenotype upon tumor cells.