A long non-coding RNA named HOTTIP (HOXA transcript at the distal tip) coordinates the activation of various 5' HOXA genes which encode master regulators of development through targeting the WDR5/MLL complex. HOTTIP acts as an oncogene in several types of cancers, whereas its biological function in gastric cancer has never been studied. In the present study, we investigated the role of HOTTIP in gastric cancer. We found that HOTTIP was upregulated in gastric cancer cell lines. Knockdown of HOTTIP in gastric cancer cells inhibited cell proliferation, migration and invasion. Moreover, downregulation of HOTTIP led to decreased expression of homeobox protein Hox-A13 (HOXA13) in gastric cancer cell lines. HOXA13 was involved in HOTTIP‑induced malignant phenotypes of gastric cancer cells. Our data showed that the levels of HOTTIP and HOXA13 were both markedly upregulated in gastric cancer tissues compared with their counterparts in non-tumorous tissues. Furthermore, the expression levels of HOTTIP and HOXA13 were both higher in gastric cancer which was poorly differentiated, at advanced TNM stages and exhibited lymph node-metastasis. Spearman analyses indicated that HOTTIP and HOXA13 had a highly positive correlation both in non-tumor mucosae and cancer lesions. Collectively, these findings suggest that HOTTIP and HOXA13 play important roles in gastric cancer progression and provide a new insight into therapeutic treatment for the disease.
PurposeDiffuse midline gliomas (DMG) with H3K27M mutations have been identified as a rare distinctive entity with unique genetic features, varied molecular alterations, and poor prognosis. The current study aimed to evaluate the clinical characteristics and profile of molecular markers on patients with a DMG harboring H3K27M mutations, and explore the impact of this genetic makeup on overall survival.MethodsWe retrospectively analyzed 43 consecutive patients diagnosed with a DMG harboring H3K27M mutations (age range 3 to 75 years) and treated in a tertiary institution within China between January 2017 to December 2019. Various clinical and molecular factors were evaluated to assess their prognostic value in this unique patient cohort.ResultsThe median overall survival (OS) was 12.83 months. Preoperative Karnofsky Performance Score (KPS) and adjuvant radiotherapy were found to be independent clinical parameters influencing the OS by multivariate analysis (p = 0.027 and p < 0.001 respectively). Whereas extent of tumor resection failed to demonstrate statistical significance. For molecular markers, P53 overexpression was identified as a negative prognostic factor for overall survival by multivariate analysis (p = 0.030).ConclusionLow preoperative KPS, absence of radiotherapy and P53 overexpression were identified as predictors of a dismal overall survival in patients with DMG and H3K27M mutations.
Circulating brain-derived neurotrophic factor (BDNF) has been highlighted as being a key regulator of rehabilitation-induced recovery after stroke. The aim of this study was to evaluate the association between serum levels of BDNF and functional outcome and mortality events in a 3-month follow-up study in a cohort of patients with an acute ischemic stroke (AIS). From January 2015 to December 2015, consecutive first-ever AIS patients admitted to the Department of Emergency of our hospital were identified. Serum BDNF levels were measured at admission. Functional outcome was evaluated at 3 months using the modified Rankin scale (m-Rankin). We used logistic regression models to assess the relationship between BDNF levels and functional outcome or mortality. In this study, 204 patients were included. Patients with poor outcomes and non-survivors had significantly lower BDNF levels on admission (P < 0.0001 all). Multivariate logistic regression analysis adjusted for common risk factors showed that BDNF levels in the lowest interquartile (≤1st 9.2 ng/ml) was an independent predictor of functional outcome (odds ratios [OR] = 3.75; 95 % confidence interval [CI], 2.43-8.12) and mortality (OR = 4.04; 95 % CI, 2.07-9.14). The area under the receiver operating characteristic curve of BDNF was 0.77 (95 % CI, 0.70-0.84) for functional outcome and 0.79 (95 % CI, 0.71-0.86) for mortality. The findings indicated that low serum levels of BDNF at admission were significantly associated with poor short-term functional outcome and mortality, suggesting that BDNF may serve as a biomarker of poor function outcome after stroke.
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