Identification and Genetic Analysis of a Factor IX Gene Intron 3 Mutation in a Hemophilia B Pedigree in China.

OBJECTIVE: Hemophilia B is caused by coagulation defects in the factor IX gene located in Xq27.1 on the X chromosome. A wide range of mutations, showing extensive molecular heterogeneity, have been described in hemophilia B patients. Our study was aimed at genetic analysis and prenatal diagnosis of hemophilia B in order to further elucidate the pathogenesis of the hemophilia B pedigree in China. MATERIALS AND METHODS: Polymerase chain reaction amplification and direct sequencing of all the coding regions was conducted in hemophilia B patients and carriers. Prenatal diagnosis of the proband was conducted at 20 weeks. RESULTS: We identified the novel point mutation 10.389 A>G, located upstream of the intron 3 acceptor site in hemophilia B patients. The fetus of the proband's cousin was identified as a carrier. CONCLUSION: Our identification of a novel mutation in the F9 gene associated with hemophilia B provides novel insight into the pathogenesis of this genetically inherited disorder and also represents the basis of prenatal diagnosis.

LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer.

Trastuzumab resistance is leading cause of mortality in HER2-positive breast cancers, and the role of TGF-ß-induced epithelial-mesenchymal transition (EMT) in trastuzumab resistance is well established, but the involvement of lncRNAs in trastuzumab resistance is still unknown. Here, we generated trastuzumab-resistant breast cancer cells with increased invasiveness compared with parental cells, and observed robust epithelial-mesenchymal transition (EMT) and consistently elevated TGF-ß signaling in these cells. We identified long noncoding RNA activated by TGF-ß (lnc-ATB) was the most remarkably upregulated lncRNA in TR SKBR-3 cells and the tissues of TR breast cancer patients. We found that lnc-ATB could promote trastuzumab resistance and invasion-metastasis cascade in breast cancer by competitively biding miR-200c, up-regulating ZEB1 and ZNF-217, and then inducing EMT. In addition, we also found that the high level of lnc-ATB was correlated with trastuzumab resistance of breast cancer patients. Thus, these findings suggest that lncRNA-ATB, a mediator of TGF-ß signaling, could predispose breast cancer patients to EMT and trastuzumab resistance.

Clinical value of serum HMGB1 in diagnosis and prognosis of laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignancies in the head and neck region. Recently, aberrantly expressed high-mobility group box 1 (HMGB1) has received a great deal of attention as a potential biomarker for cancer diagnosis and prognosis. Therefore, the aim of this study was to estimate HMGB1 levels in serum in LSCC patients and healthy controls and evaluated the potential of serum HMGB1 as a noninvasive biomarker for diagnosis and prognosis in LSCC. Serum HMGB1 levels were analyzed in 71 LSCC patients and 50 healthy controls. The serum HMGB1 level was significantly higher in LSCC patients compared with the healthy controls (4.81 ± 2.33 vs. 3.21 ± 1.08 ng/mL, P < 0.001). High serum HMGB1 was significantly associated with T classification (P = 0.005), N classification (P = 0.002), and clinical stage (P = 0.001). The area under ROC curve was 0.716, and the sensitivity and specificity were 42.3 and 92.0%, respectively. The Kaplan-Meier plots showed that patients with high serum HMGB1 had a poorer overall survival than those with low serum HMGB1 (P = 0.036). Serum HMGB1 levels are significantly associated with the progression of LSCC. In this population, HMGB1 has a poor sensitivity, but a high specificity for the diagnosis of LSCC. Serum HMGB1 level has potential as a biomarker for the prognosis in LSCC patients.

[The expressions of IL-7 and IL-7R and the relationship between them with lymph node metastasis and prognosis in non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: it has been proven that lymph node metastasis was closely related to prognosis of lung cancer. Interleukin-7 (IL-7) and interleukin-7 receptor (IL-7R) could promote lymph node metastasis through vascular endothelial growth factor-D (VEGF-D). The aim of this study is to explore the expressions of IL-7 and IL-7R in lung cancer and the relationship between them with lymph node metastasis and prognosis in non-small cell lung cancer (NSCLC). METHODS: the expressions of IL-7 and IL-7R in 95 cases of NSCLC were detected with immunohistochemistry method and the relationship between IL-7 and IL-7R and their impact on lung cancer patients' outcomes were analyzed. RESULTS: in 95 cases of NSCLC, the high expression rates of IL-7, IL-7R and VEGF-D were 63.16%, 61.05% and 58.95%. The expressions of IL-7 and IL-7R were correlated closely with clinic stage and lymph node metastasis, but had no relationship with age, gender, histological type and differentiation degree. The lymphatic vessel density (LVD) mean of the group with high expressions of IL-7 and IL-7R was higher than that with low or negative expressions of IL-7 and IL-7R, and they were significant different in statistics. Log-rank analysis showed that the postoperative survival period was significantly shorter in high expression groups IL-7, IL-7R and VEGF-D comparing with that in low or negative groups. CONCLUSIONS: the high expression of IL-7 and IL-7R is highly positie correlated with clinic stage, lymph node metastasis, VEGF-D, LVD and poor prognosis in Non-small cell lung cancer.