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Abstract Background The secretory small GTPase Rab27b was recently identified as an oncogene in breast cancer (BC) in vivo and in vitro studies. This research was designed to further explore the clinical and prognostic significance of Rab27B in BC patients. Methods The mRNA/protein expression level of Rab27B was examined by performing Real-time PCR, western blot, and immunohistochemistry (IHC) assays in 12 paired BC tissues and matched adjacent noncancerous tissues (NAT). Then we carried out IHC assay in a large cohort of 221 invasive BC tissues, 22 normal breast tissues, 40 fibroadenoma (FA), 30 ductual carcinoma in situ (DCIS) and 40 metastatic lymph nodes (LNs). The receiver operating characteristic curve method was applied to obtain the optimal cutoff value for high Rab27B expression. Epithelial-mesenchymal transition (EMT) marker expression levels were detected in relation to Rab27B expression. Results We observed that the increased expression of Rab27B was dependent upon the magnitude of cancer progression (P P Conclusion Our findings suggest that overexpression of Rab27B in BC coincides with lymph node metastasis and acquisition of a poor prognostic phenotype.

Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is an aggressive disease, and no standard treatment and validated prognostic model were established. Serum sIL-2Rα levels were measured in 94 ENKTL patients to evaluate its relationship with clinical features, treatment response, and prognosis. Serum sIL-2Rα level was 2964 ± 1613.6 ng/L in ENKTL patients, higher than in normal healthy controls (p < 0.05). Using median level (2508.5 ng/L) as cutoff, patients were divided into higher- and lower-level group (N = 47 for each). The complete remission and overall remission rate were significantly higher in lower-level group (p < 0.05). After a median follow-up time of 22.0 months, 2-year overall survival and progression-free survival rates were 60.0 and 53.0 %, respectively. Lower sIL-2Rα level significantly correlated with better progression-free survival (PFS) and overall survival (OS) (p = 0.001 and 0.002, respectively). IPI score and treatment responses after 2 cycles of chemotherapy significantly correlated with PFS and OS (p < 0.05). In a multivariate Cox regression model that included IPI score, treatment responses, and sIL-2Rα level, all three parameters were independent prognostic factors for OS (p = 0.043, 0.001, and 0.025, respectively), and the last two parameters were also independent factors for PFS (p = 0.005 and 0.005, respectively). Elevated serum sIL-2Rα level was related to poor responses to treatments and can be used as a valuable biomarker for disease activity. Moreover, serum sIL-2Rα was an independent prognostic factor for both OS and PFS. These results need to be validated in prospective trials and may support the incorporation of anti-CD25 targeted therapy into the treatment realm of ENKTL.

Purpose: Currently, nasopharyngeal carcinoma (NPC) prognosis evaluation is based primarily on the TNM staging system. This study aims to identify prognostic markers for NPC., Patients and Methods: We detected expression of 18 biomarkers by immunohistochemistry in NPC tumors from 209 patients and evaluated the association between gene expression level and disease-specific survival (DSS). We used support vector machine (SVM)--based methods to develop a prognostic classifier for NPC (NPC-SVM classifier). Further validation of the NPC-SVM classifier was performed in an independent cohort of 1,059 patients., Results: The NPC-SVM classifier integrated patient sex and the protein expression level of seven genes, including Epstein-Barr virus latency membrane protein 1, CD147, caveolin-1, phospho-P70S6 kinase, matrix metalloproteinase 11, survivin, and secreted protein acidic and rich in cysteine. The NPC-SVM classifier distinguished patients with NPC into low- and high-risk groups with significant differences in 5-year DSS in the evaluated patients (87% v 37.7%; P < .001) in the validation cohort. In multivariate analysis adjusted for age, TNM stage, and histologic subtype, the NPC-SVM classifier was an independent predictor of 5-year DSS in the evaluated patients (hazard ratio, 4.9; 95% CI, 3.0 to 7.9) in the validation cohort., Conclusion: As a powerful predictor of 5-year DSS among patients with NPC, the newly developed NPC-SVM classifier based on tumor-associated biomarkers will facilitate patient counseling and individualize management of patients with NPC.

Introduction: MicroRNAs (miRNAs) are a class of small non-coding RNAs (20 to 24 nucleotides) that post-transcriptionally modulate gene expression. A key oncomir in carcinogenesis is miR-21, which is consistently up-regulated in a wide range of cancers. However, few functional studies are available for miR-21, and few targets have been identified. In this study, we explored the role of miR-21 in human breast cancer cells and tissues, and searched for miR-21 targets., Methods: We used in vitro and in vivo assays to explore the role of miR-21 in the malignant progression of human breast cancer, using miR-21 knockdown. Using LNA silencing combined to microarray technology and target prediction, we screened for potential targets of miR-21 and validated direct targets by using luciferase reporter assay and Western blot. Two candidate target genes (EIF4A2 and ANKRD46) were selected for analysis of correlation with clinicopathological characteristics and prognosis using immunohistochemistry on cancer tissue microrrays., Results: Anti-miR-21 inhibited growth and migration of MCF-7 and MDA-MB-231 cells in vitro, and tumor growth in nude mice. Knockdown of miR-21 significantly increased the expression of ANKRD46 at both mRNA and protein levels. Luciferase assays using a reporter carrying a putative target site in the 3' untranslated region of ANKRD46 revealed that miR-21 directly targeted ANKRD46. miR-21 and EIF4A2 protein were inversely expressed in breast cancers (rs = -0.283, P = 0.005, Spearman's correlation analysis)., Conclusions: Knockdown of miR-21 in MCF-7 and MDA-MB-231 cells inhibits in vitro and in vivo growth as well as in vitro migration. ANKRD46 is newly identified as a direct target of miR-21 in BC. These results suggest that inhibitory strategies against miR-21 using peptide nucleic acids (PNAs)-antimiR-21 may provide potential therapeutic applications in breast cancer treatment.