Yunduo Liu

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.

Overexpression of multiple myeloma SET domain (MMSET) is associated with advanced tumor aggressiveness and poor prognosis in serous ovarian carcinoma

Abstract Multiple myeloma SET domain (MMSET) has been shown to be overexpressed in many different cancer tissues. Our study was to investigate the expression of MMSET in serous ovarian carcinoma and to evaluate its clinical significance in patients with serous ovarian carcinoma. Immunohistochemistry was performed to determine the expression of MMSET in 132 serous ovarian carcinoma, 32 normal ovarian and fallopian tube specimens. The high expression of MMSET was observed in 49.2% (65/132) in patients with serous ovarian carcinoma. MMSET high expression correlated with the advanced extent of serous ovarian carcinoma and poor outcome. MMSET may serve as a new molecular marker to predict the prognosis of serous ovarian carcinoma in the clinic.

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.

Overexpression of eukaryotic initiation factor 5A2 (EIF5A2) is associated with cancer progression and poor prognosis in patients with early-stage cervical cancer

As one of the only two isoforms of the eukaryotic initiation factor (EIF)5A family, EIF5A2 plays an important role in tumour progression and prognosis evaluation. The aim of this study was to investigate EIF5A2 expression in International Federation of Gynecology and Obstetrics (FIGO) stage I–II cervical cancer and to evaluate its clinical significance.

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.

Identification of Subpathway Signatures For Ovarian Cancer Prognosis by Integrated Analyses of High-Throughput miRNA and mRNA Expression

Background/Aims: Ovarian cancer (OC) causes more death and serious conditions than any other female reproductive cancers, and many expression signatures have been identified for OC prognoses. However, no significant overlap is found among signatures from different studies, indicating the necessity of signature identifications at the functional level. Methods: We performed an integrated analyses of miRNA and gene expressions to identify OC prognostic subpathways (pathway regions). Using The Cancer Genome Atlas data set, we identified core prognostic subpathways, and calculated subpathway risk scores using both miRNA and gene components. Finally, we performed global risk impact analyses to optimize core subpathways using the random walk algorithm. Results: Subpathway-level analyses displayed more robust results than the gene- and miRNA-level analyses. Moreover, we verified the advantage of core subpathways over the entire pathway-based results and their prognostic performance in two independent validation data sets. Based on the global impact score, 13 subpathway signatures were selected and a combined subpathway-based risk score was further calculated for OC patient prognoses. Conclusions: Overall, it was possible to systematically perform integrated analyses of the expression levels of miRNAs and genes to identify prognostic subpathways and infer subpathway risk scores for use in OC clinical applications.