Xiaoming Ning

LAPTM4B overexpression is a novel independent prognostic marker for metastatic ovarian tumors.

Objective Metastatic ovarian tumors are a series of lethal carcinomas that almost always have bad prognosis. Their prognoses, however, vary depending on the primary tumor malignancies of each. It has been reported that LAPTM4B, a novel tumor-associated gene, might indicate a worse prognosis when it was overexpressed in other carcinomas. Therefore, the authors expected to investigate whether LAPTM4B overexpression is an independent prognostic marker in metastatic ovarian tumors. Methods Immunohistochemistry was used to assess LAPTM4B expression in metastatic ovarian tumors from 102 patients. Subsequently, univariate and multivariate survival analyses with Cox regression were performed to determine the association between LAPTM4B expression and prognosis. To identify any differences in prognosis between the 2 groups of patients with differing primary malignancies, the log-rank test was used. Results The median overall and progression-free survival rates of patients with tumors of gastrointestinal tract origin were 0.97 and 0.51 years, respectively, and both were statistically significantly lower than those of patients with tumors of breast origin (P < 0.0001), which were 2.68 and 1.96 years, accordingly. Of 102 patients, 77 were classified as having a high expression of LAPTM4B, and LAPTM4B expression had a significant association with the prognosis of metastatic ovarian tumors (P < 0.01); no statistically significant interaction between LAPTM4B expression and primary malignancies was detected (P > 0.1). On the other hand, medians of overall survival and progression-free survival of patients with tumors of gastrointestinal tract origin were significantly lower than those of patients with tumors of breast origin (P < 0.0001). Conclusions Patients with metastatic ovarian tumors of breast origin had significantly better prognosis than those with the disease from gastrointestinal tract primary malignancies. LAPTM4B overexpression might be an independent prognostic marker of metastatic ovarian tumors.

Overexpression of MMSET in endometrial cancer: A clinicopathologic study

Endometrial cancer is a common gynecologic malignancy. It has been reported that overexpression of multiple myeloma SET (MMSET) promoted cellular adhesion, clonogenic growth, and tumorigenicity in other carcinomas. Therefore, the authors expected to investigate whether MMSET overexpression is an independent prognostic marker in endometrial cancer.

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 TNFAIP8 is associated with tumor aggressiveness and poor prognosis in patients with invasive ductal breast carcinoma

Tumor necrosis factor α-induced protein 8 (TNFAIP8), a transcription factor nuclear factor κB-inducible, antiapoptotic and oncogenic molecule, is associated with prognosis of several human malignancies. However, the relationship between TNFAIP8 and the prognosis of the invasive ductal carcinoma (IDC) of the breast remains unclear. TNFAIP8 expression was evaluated using real-time polymerase chain reaction (PCR) and Western blot analysis in 20 fresh IDC tissues and immunohistochemical analysis in 351 paraffin-embedded IDC tissues. Real-time PCR and Western blot analysis demonstrated that both TNFAIP8 messenger RNA and protein were up-regulated in IDC tissues compared with the paired adjacent noncancerous tissues. Immunohistochemistry revealed that TNFAIP8 expression was significantly correlated with some clinicopathological factors, including axillary lymph node metastasis (P=.001), advanced TNM stage (P<.001), high histologic grade (P<.001), molecular subtype (P<.001), and postoperative recurrence (P<.001). Univariate and multivariate logistic regression analyses demonstrated that TNFAIP8 overexpression was strongly associated with axillary lymph node metastasis (odds ratio, 1.818; 95% confidence interval, 1.167-2.832; P=.008). Moreover, Kaplan-Meier analysis indicated that IDC patients with high TNFAIP8 expression had a shorter survival time than did those with low TNFAIP8 expression, and multivariate analysis indicated that TNFAIP8 was an independent prognostic factor for overall survival and disease-free survival in IDC (P=.041 and P=.020, respectively). Therefore, TNFAIP8 overexpression may contribute to tumor progression, and it may be a novel prognostic biomarker for the patients with IDC.

Aberrant expression of δ-like ligand 4 contributes significantly to axillary lymph node metastasis and predicts postoperative outcome in breast cancer.

δ-Like ligand 4 (DLL4), a ligand for the Notch family of receptors, forecasts the prognosis of several human malignancies. However, the expression and role of DLL4 in breast cancer remain largely unknown. In the present study, we first evaluated whether the overexpression of DLL4 could be used as an indicator of axillary lymph node metastasis and postoperative prognosis in breast cancer. The amount of DLL4 protein was assessed in 204 tumor specimens by immunohistochemical staining. Overexpression was detected in 142 (69.6%) and significantly associated with advanced TNM stage (III versus I, P = .031; III versus II, P = .038), axillary lymph node metastasis (P = .001), and postoperative recurrence (P = .007). Moreover, using univariate and multivariate logistic regression analysis, we found that DLL4 overexpression was strongly associated with axillary lymph node metastasis (odds ratio, 3.036; 95% confidence interval [CI], 1.561, 5.902; P = .001). Lastly, survival analysis showed that patients with low DLL4 expression had a significantly better overall survival and disease-free survival than patients with high DLL4 expression. Furthermore, in multivariate analysis, DLL4 overexpression was an independent risk factor for unfavorable overall survival (hazard ratio, 2.662; 95% CI, 1.300, 5.452; P = .007) and disease-free survival (hazard ratio, 2.568; 95% CI, 1.353, 4.876; P = .004). Taken together, these results suggest that high expression of DLL4 is associated with axillary lymph node metastasis and a poor prognosis in breast cancer, suggesting its value as a diagnostic marker for breast cancer.

LAPTM4B Predicts Axillary Lymph Node Metastasis in Breast Cancer and Promotes Breast Cancer Cell Aggressiveness in Vitro

Purpose: Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is associated with the prognosis of several human malignancies. In this study, the role of LAPTM4B in the metastatic potential of breast cancer (BC) and its underlying molecular mechanisms were investigated. Methods: The relationship between LAPTM4B expression and axillary lymph node metastasis was determined in 291 BC specimens by immunohistochemistry. The expression of LAPTM4B in paired BC cells was overexpressed and inhibited to analyse the role of LAPTM4B in the aggressiveness of BC. Cell proliferation, migration and invasion were assessed in vitro. Metastasis-related protein levels were detected through Western blot. Results: Immunohistochemical staining demonstrated that high expression level of LAPTM4B was independently associated with axillary lymph node metastasis (odds ratio=2.428; 95%CI=1.333- 4.425; P=0.004). The LAPTM4B inhibition in MCF-7 cells inhibited cell proliferation, migration, invasion, and resulted in simultaneous downregulation of phosphorylated N-cadherin, vimentin, and upregulation of E-cadherin. By contrast, the LAPTM4B overexpression promoted cell proliferation, migration, invasion, and led to simultaneous upregulation of N-cadherin, vimentin, and downregulation of E-cadherin in T47D cells. Conclusions: High expression level of LAPTM4B predicts tumor metastatic potential in patients with BC. Our results provide the first evidence of the role of LAPTM4B as an Epithelial-mesenchymal transition (EMT) inducer that promotes aggressiveness in BC cells.

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.