Xiuwei Chen

The long-term efficacy of neoadjuvant chemotherapy followed by radical hysterectomy compared with radical surgery alone or concurrent chemoradiotherapy on locally advanced-stage cervical cancer.

Objectives: The purpose of this study was to compare the long-term survival of patients with locally advanced cervical cancer (stages IB2-IIB) treated with neoadjuvant chemotherapy followed by radical hysterectomy (hysterectomy plus pelvic lymph node dissection) (NACT + RS) with the survival of those treated with radical surgery (hysterectomy plus pelvic lymph node dissection) (RS) or concurrent chemoradiotherapy (CCRT). Methods: A retrospective study was performed. Patients were followed up for 54 to 114 months (median, 82.8 months). All risk factors that may have affected the disease-free survival (DFS) and overall survival (OS) were assessed. Results: From January 2000 to December 2005, 476 eligible patients were followed up. The 5-year DFS rates of the NACT + RS, RS, and CCRT groups were 85.00%, 77.44%, and 52.94%, respectively (P < 0.0001), whereas the 5-year OS rates were 88.67%, 80.21% and 64.37%, respectively (P < 0.0001). The NACT + RS group had significantly higher survival rates than both the RS (DFS: hazard ratio = 1.870, P = 0.0031; OS: hazard ratio = 1.813, P = 0.0175) and CCRT (DFS: hazard ratio = 3.535, P < 0.0001; OS: hazard ratio = 3.157, P < 0.0001) groups, while adjusting for the pathological type, clinical stage, tumor size (initial), and age. The 5-year DFS rate for patients receiving TP (paclitaxel and cisplatin) was 90.55%, and 71.70% for patients receiving PVB (cisplatin, vincristine, and bleomycin); the 5-year OS rates were 96.75% for TP and 70.09% for PVB, respectively. Patients receiving TP had a statistically significant improvement in both 5-year DFS and OS rates (P < 0.001). Conclusions: Neoadjuvant NACT + RS improves the long-term DFS and OS of patients with locally advanced cervical cancer stage IB2-IIB compared with RS alone and especially compared with CCRT. In the NACT + RS group, NACT with TP improves the long-term DFS and OS of patients compared with patients who had PVB chemotherapy regimen. These results may provide some useful information for clinicians to treat patients with locally advanced cervical carcinoma.

Over‐expression of LAPTM4B is associated with poor prognosis and chemotherapy resistance in stages III and IV epithelial ovarian cancer

The purpose of this study was to determine whether LAPTM4B over‐expression is associated with the prognosis and chemotherapy resistance in patients with stages III and IV epithelial ovarian carcinoma, i.e., patients with peritoneal metastasis or lymph node metastasis of epithelial ovarian carcinoma.

LAPTM4B Down Regulation Inhibits the Proliferation, Invasion and Angiogenesis of HeLa Cells In Vitro

Background/Aims: LAPTM4B (lysosome-associated protein transmembrane 4 beta) is a novel oncogene with important functions in aggressive human carcinomas, including cervical cancer. However, the specific functions and internal molecular mechanisms associated with this gene in the context of cervical cancer remain unclear. Methods: In this study, we explored the effects and mechanisms of LAPTM4B on tumor growth, metastasis and angiogenesis in vitro by depletion of LAPTM4B in Hela cell. RNA interference was used to induce down regulation of LAPTM4B gene expression in Hela cells. The motility, migration potential, and proliferation of the Hela cells were measured by flow cytometry, Transwell migration assays, wound healing assays, and Cell Counting Kit-8 assays. In addition, the cell cycle analysis utilized fluorescence-activated cell sorting. Results: In this study, RNAi-mediated LAPTM4B knockdown inhibited cell growth and angiogenesis. In vitro, HeLa cells with down regulated LAPTM4B also exhibited decreased migration and invasion activity as well as significantly reduced CDK12, HIF-1α, MMP-2, MMP-9 and VEGF expression. LAPTM4B blockade significantly decreased cord lengths and branch points in a tube formation assay. Conclusions: These results suggested that LAPTM4B inactivation could be a novel therapeutic target for cervical cancer.

Overexpression of Wnt7a is associated with tumor progression and unfavorable prognosis in endometrial cancer.

Background Wnt7a is a secreted glycoprotein that regulates normal cellular proliferation and differentiation, as well as tumorigenesis and progression. The aim of the present study was to detect the level of expression of Wnt7a in endometrial cancer and explore its role in progression and prognosis of endometrial cancer. Methods Immunohistochemistry was used to examine the expression of Wnt7a in 244 endometrial cancer specimens, in 48 benign endometrial lesion specimens, and 43 normal endometrium specimens. &khgr;2 Analysis, Kaplan-Meier analysis and log-rank test, and multivariate Cox proportional hazards analysis were applied for statistical analysis. Results Wnt7a was overexpressed in endometrial cancer compared with normal endometrium and benign endometrial lesion (both P < 0.001). Wnt7a expression was correlated with histological grade, International Federation of Gynecology and Obstetrics stage, depth of myometrial invasion, vascular/lymphatic invasion, and lymph node metastasis. The results of Kaplan-Meier analysis indicated that Wnt7a expression was associated with overall survival (OS) and disease-free survival (DFS) of endometrial cancer. The survival of negative expression Wnt7a group had longer OS and DFS compared with the group with positive expression. The difference was significant (both P < 0.001, log-rank test). Multivariate Cox regression analysis revealed that Wnt7a expression status was an independent prognostic factor for both OS and DFS (P = 0.034 and P = 0.009, respectively) of patients with endometrial cancer. Conclusions Overexpression of Wnt7a may contribute to the progression of endometrial cancer and thus may serve as a new biomarker to predict the prognosis of endometrial cancer.

The toxicity and long-term efficacy of nedaplatin and paclitaxel treatment as neoadjuvant chemotherapy for locally advanced cervical cancer†

The use of neoadjuvant chemotherapy (NACT) for the treatment of locally advanced cervical cancer (LACC) remains controversial. In current clinical practice, platinum‐based chemotherapy is the major option for patients with LACC. However, serious adverse events have been reported after platinum‐based chemotherapy treatment for LACC patients. In this study, the authors evaluated whether nedaplatin and paclitaxel (NP), as a new NACT regimen, offers less toxicity and better long‐term efficacy for LACC (stages IB2‐IIB) treatment. Comparisons between NP and paclitaxel and cisplatin (PC) in terms of toxicity and long‐term efficacy are also presented.

Evaluation of chemotherapy response with serum squamous cell carcinoma antigen level in cervical cancer patients: a prospective cohort study.

MRI does not always reflect tumor response after chemotherapy. Therefore, it is necessary to explore additional parameters to more accurately evaluate tumor response for the subsequent clinical determination about radiotherapy or radical surgery. A training cohort and an external validation cohort were used to examine the predictive performance of SCC-ag to evaluate tumor response from teaching hospital of Harbin Medical University. The study included 397 women with SCC (age: 28–73 years). Patients consecutively enrolled between August 2008 and January 2010 (n = 205) were used as training cohort. Patients consecutively enrolled between February 2010 and May 2011 (n = 192) were used as validation cohort. A multivariate regression analysis of the data from the training cohort indicated that serum SCC-ag level is an independent factor for neo-adjuvant chemotherapy (NACT) response. Analysis of the data from the validation cohort suggested that chemotherapy response could be more accurately predicted by SCC-ag than by magnetic resonance imaging (MRI) (sensitivity (Se): 0.944 vs. 0.794; specificity (Sp): 0.727 vs. 0.636; positive predictive value (PPV): 0.869 vs. 0.806; negative predictive value (NPV): 0.873 vs. 0.618; the area under ROC curve (AUC): 0.898 vs. 0.734). Combining SCC-ag with MRI was more powerful than MRI alone (Se: 0.952 vs. 0.794; Sp: 0.833 vs. 0.636; PPV: 0.916 vs. 0.806; NPV: 0.902 vs. 0.618; AUC: 0.950 vs. 0.734). Our study indicates that serum SCC-ag level is a sensitive and reliable measure to evaluate cervical cancer response to chemotherapy. Using SCC-ag in combination with MRI findings further improves the predictive power.

Overexpression of Lysine-Specific Demethylase 1 Is Associated With Tumor Progression and Unfavorable Prognosis in Chinese Patients With Endometrioid Endometrial Adenocarcinoma:

Objective Lysine-specific demethylase 1 (LSD1) is a kind of flavin adenine dinucleotide–dependent amine oxidase that regulates normal cellular differentiation, gene activation, tumorigenesis, and progression. This study aims to detect the expression level of LSD1 in endometrial cancer and to explore its role in the progression and prognosis of endometrioid endometrial adenocarcinoma (EEA). Methods Immunohistochemistry was used to examine the expression of LSD1 in 206 EEA specimens, 50 benign endometrial lesion specimens, and 45 normal endometrium specimens. &khgr;2 Analysis, Kaplan-Meier method, and multivariate Cox proportional hazard analysis were applied for the statistical analysis. Results Compared with normal endometrium and benign endometrial lesion (both P < 0.001), LSD1 was overexpressed in EEA. LSD1 expression was correlated with histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, vascular/lymphatic invasion, depth of myometrial invasion, and lymph node metastasis. Results of the Kaplan-Meier analysis indicated that LSD1 expression was associated with overall survival (OS) and disease-free survival (DFS) of EEA. The negative expression LSD1 group had longer OS and DFS than did the positive expression group. The difference was significant (both P < 0.001, log-rank test). Multivariate Cox regression analysis revealed that the LSD1 expression status was an independent prognostic factor for both OS (P = 0.027) and DFS (P = 0.016) of patients with EEA. Conclusions Overexpression of LSD1 may contribute to the progression of EEA and may thus serve as a new biomarker to predict the prognosis of EEA.

Special AT-rich sequence-binding protein 1: a novel biomarker predicting cervical squamous cell carcinoma prognosis and lymph node metastasis

OBJECTIVE Special AT-rich sequence-binding protein 1 is aberrantly expressed in various malignant tumors. However, the expression and function of special AT-rich sequence-binding protein 1 in cervical squamous cell carcinoma have not been reported. The objective of this study was to investigate the clinical significance of special AT-rich sequence-binding protein 1 in cervical squamous cell carcinoma. METHODS In this study, we investigated the expression of special AT-rich sequence-binding protein 1 through immunohistochemistry in 25 normal cervix specimens and 167 cervical squamous cell carcinomas and analyzed its association with various clinicopathologic parameters, including patient outcome. RESULTS Special AT-rich sequence-binding protein 1 protein was detected in 58 (34.7%) out of 167 patients and was highly related to International Federation of Gynecology and Obstetrics stage, histologic grade, lymph node metastasis, vascular-lymphatic invasion and recurrence of cervical squamous cell carcinoma. Patients with positive special AT-rich sequence-binding protein 1 expression had significantly lower overall survival and disease-free survival compared with patients with negative expression of special AT-rich sequence-binding protein 1 (P = 0.001 and P < 0.001, respectively). A multivariate Cox regression analysis revealed that special AT-rich sequence-binding protein 1 was an independent prognostic marker for both disease-free survival and overall survival of cervical squamous cell carcinoma patients (P = 0.038 and P = 0.010, respectively). A multivariate logistic regression analysis showed that special AT-rich sequence-binding protein 1 expression was strongly associated with lymph node metastasis (odds ratio = 2.497; P = 0.032). Sensitivity and specificity of special AT-rich sequence-binding protein 1 for lymph node metastasis were 61.0 and 73.8%, respectively. CONCLUSIONS These results showed that special AT-rich sequence-binding protein 1 expression was associated with tumor progression, metastasis and poor prognosis in cervical squamous cell carcinoma. It may serve as a new prognostic biomarker or a target for improving the treatment efficiency of patients with cervical squamous cell carcinoma.

Overexpression of special AT-rich sequence-binding protein 1 in endometrial cancer: a clinicopathologic study.

Objective Special AT-rich sequence-binding protein 1 (SATB1), as a genome organizer, serves important functions in tumor progression and metastasis. The SATB1 is overexpressed in various malignant tumors. However, the expression and prognostic value of SATB1 in endometrial cancer remain unknown. The aim of this study was to explore the prognostic values of SATB1 expression in endometrial cancer. Methods/Materials We investigated the expression of SATB1 in 172 untreated endometrial cancer tissues and 25 normal endometrial tissues through immunohistochemical staining. We also analyzed the association of SATB1 level with clinicopathologic parameters and determined its prognostic significance. Result Special AT-rich sequence-binding protein 1 was expressed in 78 (45.3%) of the 172 endometrial cancer samples, but not in the normal endometrial samples. The positive expression of SATB1 was associated with clinicopathologic factors, such as International Federation of Gynecology and Obstetrics stage, histological grade, myometrial invasion depth, lymph node metastasis, vascular/lymphatic invasion, and recurrence. The patients with positive SATB1 expression had worse overall survival and disease-free survival rates than the patients with negative SATB1 expression (P < 0.001 for both). Multivariate Cox analysis indicated that SATB1 was an independent parameter for overall survival (hazards ratio, 2.928; 95% confidence interval, 1.072–7.994; P = 0.036) and disease-free survival (hazards ratio, 2.825; 95% confidence interval, 1.111–7.181; P = 0.029). Conclusions Results showed that SATB1 may be involved in tumor development and progression in endometrial cancer, may serve as a promising biomarker for predicting the prognosis of endometrial cancer patients, and thus may act as a novel target for treating endometrial carcinoma.

Overexpression of Siah2 Is Associated With Poor Prognosis in Patients With Epithelial Ovarian Carcinoma.

Objectives Seven in absentia homolog 2 (Siah2) is an E3 ubiquitin ligase that is expressed in mammals and is homologous to seven in absentia in Drosophila. Siah2 is involved in the progression of many malignancies. However, the role of Siah2 in ovarian cancer remains unclear. This study aims to evaluate the prognostic value of Siah2 expression for epithelial ovarian carcinoma (EOC) patients. Materials and Methods Immunohistochemical analysis was conducted using 32 normal ovarian specimens and 122 ovarian carcinoma specimens, respectively. We analyzed the correlations of Siah2 expression with the clinicopathological factors and prognosis of ovarian cancer patients. &khgr;2 Analysis, Kaplan-Meier method, and multivariate Cox proportional hazard analysis were conducted for statistical analyses. Results Immunohistochemical staining demonstrated that the expression of Siah2 was higher in the EOC tissues than in the normal tissues. High Siah2 expression positively correlated with histological grade and lymph node metastasis but not with age, histologic type, International Federation of Gynecology and Obstetrics staging, and CA125. Patients with positive Siah2 expression showed lower overall survival and disease-free survival rates than those with negative Siah2 expression (P < 0.05 for both). Multivariate Cox analysis indicated that Siah2 was an independent parameter for overall survival (hazards ratio, 2.166; 95% confidence interval, 1.182–3.970; P = 0.012) and disease-free survival (hazards ratio, 1.819; 95% confidence interval, 1.030–3.216; P = 0.039). Conclusions Siah2 is possibly involved in tumor development and progression in EOC. Thus, Siah2 is a promising biomarker for predicting the prognosis of ovarian cancer patients and may serve as a novel target for treating ovarian carcinoma.