Qiaojia Huang

Circular RNAs expression profiles in human gastric cancer

Circular RNAs (circRNAs) are implicated in a variety of cancers. However, the roles of circRNAs in gastric cancer (GC) remain largely unknown. In the current study, circRNAs expression profiles were screened in GC, using 5 pairs of GC and matched non-GC tissues with circRNA chip. Preliminary results were verified with quantitative PCR (qRT-PCR). Briefly, total of 713 circRNAs were differentially expressed in GC tissues vs. non-GC tissues (fold change ≥ 2.0, p < 0.05): 191 were upregulated, whereas 522 were downregulated in GC tissues. qRT-PCR analysis of randomly selected 7 circRNAs from the 713 circRNAs in 50 paired of GC vs. non-GC control tissues confirmed the microarray data. Gene ontology (GO) and KEGG pathway analyses showed that many circRNAs are implicated in carcinogenesis. Among differentially expressed circRNAs, hsa_circ_0076304, hsa_circ_0035431, and hsa_circ_0076305 had the highest magnitude of change. These results provided a preliminary landscape of circRNAs expression profile in GC.

Single Nucleotide Polymorphism of the Enhancer of Zeste Homolog 2 Gene rs2072408 is Associated with Lymph Node Metastasis and Depth of Primary Tumor Invasion in Gastric Cancer.

BACKGROUND The single nucleotide polymorphism (SNP) rs2072408 is located in an intron of the enhancer of zeste homolog 2 (EZH2) gene. Its role in gastric cancer (GC) has not been determined. METHODS In the present study, the genotype of (EZH2) rs2072408 and the relationship of genotype with lymph node metastasis (LNM) and the invasive depth of gastric wall (T stage) was determined in 330 patients with GC, and the association between the genotype and recurrence and survival was determined in 253 patients with GC. RESULTS The TT genotype was identified to be significantly associated with LNM [P = 0.013; odds ratio (OR), 6.49 (95% confidence interval (CI), 1.47 - 28.59)] and T stage [T1 + T2 vs. T3 + T4, p = 0.017, OR, 3.02 (95% CI, 1.22 - 7.44)]. The overall rates of LNM and T3 + T4 stage in the present study were 70.6% and 60.6%, respectively, the rates increased 23.8% and 20.0% in patients with the TT genotype. CONCLUSIONS These results suggest that the TT genotype of EZH2 (rs2072408) was associated with LNM and the depth of gastric wall invasion in patients with GC.

Elevated Preoperative Platelet to Lymphocyte Ratio Indicates Poor Survival in Patients with Resected High-grade Serous Ovarian Carcinoma.

BACKGROUND Platelet to lymphocyte ratio (PLR) is widely used as an inflammation-related cancer biomarker. However, since its prognostic importance in resected high-grade serous ovarian carcinoma (HGSC) is still unknown, we investigated the association between PLR and the prognosis in resected HGSC in this study. METHODS Details of 103 patients with HGSC who underwent ovarian resection were collected in this retrospective study. Preoperative PLR was calculated based on platelet and lymphocyte count values. A χ2 test was used to analyze the relationship between PLR and clinical variables, a Kaplan-Meier curve and log rank analysis was used to evaluate overall survival, and multivariable analysis was used to analyze the prognostic factors. RESULTS The preoperative PLR median value (188.8) was used to divide patients into two groups: the high PLR group (PLR > 188.8) and low PLR group (PLR ≤ 188.8). A high PLR was significantly associated with a higher death rate (81.6% vs. 59.3%, p = 0.013) and a shorter median overall survival time (37 months vs. 58 months, p = 0.035) during follow-up (median length = 43 months). Multivariable data further demonstrated that a high PLR was related to a two-fold increase in risk of death (hazard ratio [HR]: 2.19, 95% confidence interval (CI): 1.30 - 3.68, p = 0.003). In addition, the risk of a CA125 of > 640.0 U/mL was significantly greater in the high PLR group (odds ratio [OR]: 2.72, 95% CI: 1.18 - 6.27, p = 0.019). Multivariable analysis suggests that PLR was an independent prognostic factor for resected HGSC. CONCLUSIONS PLR has potential as a prognostic biomarker for predicting the survival of patients with resected HGSC.

Evaluation of the expression and clinical value of lncRNA AC010761.9 in human gastric adenocarcinoma

BackgroundThe current study determined the expression and clinical value of lncRNA AC010761.9 in human gastric adenocarcinoma (GA).MethodsReal-time quantitative reverse transcription (qRT)-PCR was used to detect the level of lncRNA expression in 145 GA tissues and three GA cell lines, and the correlation between its level and clinicopathologic characteristics and potential corresponding mRNA of TNF receptor-associated factor 4 gene (TRAF4) was then evaluated.ResultsElevated lncRNA AC010761.9 was detected in all 6 GA tissues by previous lncRNA expression profile microarray assay. LncRNA AC010761.9 was over-expressed in 99 of 145 GA tissues (68.3%) with an elevated fold change of up to 35.14 compared to matched paracancerous tissues (p < 0.05), and was also over-expressed in the 3 GA cell lines (MGC803, BGC823, and SGC7901) compared to the normal gastric mucosal epithelial cell line (GES-1 cells; p < 0.05) by qRT-PCR. The elevated expression of this lncRNA was related to tumor size (p = 0.028), degree of differentiation (p = 0.047), and serum carbohydrate antigen (CA19-9) and carcinoembryonic antigen (CEA) concentrations (p = 0.026 and p = 0.037, respectively). Multivariate analysis further confirmed that the expression of lncRNA AC010761.9 was related to the degree of tumor differentiation (p = 0.015). Additionally, the expression of lncRNA AC010761.9 had a positive correlation with the mRNA expression of the potentially associated gene (TRAF4) in GA tissues (r = 0.385, p < 0.01).ConclusionsLncRNA AC010761.9 may be linked to GA progression and is a potential new biomarker for GA.

AKT2 contributes to increase ovarian cancer cell migration and invasion through the AKT2-PKM2-STAT3/NF-κB axis

Multiple studies have shown that protein kinase Bβ (AKT2) is involved in the development and progression of ovarian cancer, however, its precise role remains unclear. Here we explored the underlying molecular mechanisms how AKT2 promotes ovarian cancer progression. We examined the effects of AKT2 in vitro in two ovarian cancer cell lines (SKOV3 and HEY), and in vivo by metastasis assay in nude mice. The migration and invasion ability of SKOV3 and HEY cells was determined by transwell assay. Overexpression and knockdown (with shRNA) experiments were carried out to unravel the underlying signaling mechanisms induced by AKT2. Overexpression of AKT2 led to increased expression of pyruvate kinase (PKM2) in ovarian cancer cells and in lung metastatic foci from nude mice. Elevated AKT2/PKM2 expression induced cell migration and invasion in vitro, as well as lung metastasis in vivo; silencing AKT2 blocked these effects. Meanwhile, PKM2 overexpression was unable to increase AKT2 expression. The expressions of p-PI3K, p-AKT2, and PKM2 were increased when stimulated by epidermal growth factor (EGF); however, these expressions were blocked when inhibited the PI3K by LY294002. STAT3 expression was elevated and NF-κB p65 nuclear translocation was activated both in vitro and in vivo when either AKT2 or PKM2 was overexpressed; and these effects were inhibited when silencing AKT2 expression. Taken together, AKT2 increases the migration and invasion of ovarian cancer cells in vitro and promotes lung metastasis in nude mice in vivo through PKM2-mediated elevation of STAT3 expression and NF-κB activation. In conclusion, we highlight a novel mechanism of the AKT2-PKM2-STAT3/NF-κB axis in the regulation of ovarian cancer progression, and our work suggested that both AKT2 and PKM2 may be potential targets for the treatment of ovarian cancer.

Overexpression of HER-2 Protein is a High-Risk Factor for Patients with Surgically-Resected Stage T3 Gastric Adenocarcinoma

BACKGROUND Factors associated with tumor recurrence and death in stage T3-gastric adenocarcinoma (GA) after surgical resection remain unclear. In this study, we investigated whether patients with overexpression of epidermal growth factor receptor 2 (HER-2) comprised a high-risk group. METHODS The immunohistochemistry data of HER-2 protein expression from 633 surgically-resected T3-GA tissues were collected and then retrospectively analyzed by Chi-square test, Kaplan-Meier curve, and log rank test as well as univariate and multivariate analyses. RESULTS Patients with HER-2 overexpression had increased recurrence rates and decreased median recurrence free survival times (MRFST) compared to those with low expression of HER-2 (76.3% vs. 65.4%, p = 0.004; and 18 vs. 26 months, p = 0.002, respectively). Conversely, overall survival rates and median overall survival times (MOST) were decreased in these patients (23.3% vs. 35.7%, p = 0.001 and 26 vs. 36 months, p = 0.001, respectively). HER-2 overexpression, lymph node metastasis (pN1-pN3), distant metastasis, and R1 resection margin were identified as independent prognostic factors for shorter MRFST and MOST in patients with surgically-resected T3-GA. CONCLUSIONS Overexpression of HER-2 is a simple and reliable predictor for increased recurrence and poorer survival in patients with T3-GA following surgical resection. As such, these patients may benefit from trastuzumabbased therapy.