Inhibition of hyaluronic acid degradation pathway suppresses glioma progression by inducing apoptosis and cell cycle arrest.

BACKGROUND: Abnormal hyaluronic acid (HA) metabolism is a major factor in tumor progression, and the metabolic regulation of HA mainly includes HA biosynthesis and catabolism. In glioma, abnormal HA biosynthesis is intimately involved in glioma malignant biological properties and the formation of immunosuppressive microenvironment; however, the role of abnormal HA catabolism in glioma remains unclear. METHODS: HA catabolism is dependent on hyaluronidase. In TCGA and GEPIA databases, we found that among the 6 human hyaluronidases (HYAL1, HYAL2, HYAL3, HYAL4, HYALP1, SPAM1), only HYAL2 expression was highest in glioma. Next, TCGA and CGGA database were further used to explore the correlation of HYAL2 expression with glioma prognosis. Then, the mRNA expression and protein level of HYAL2 was determined by qRT-PCR, Western blot and Immunohistochemical staining in glioma cells and glioma tissues, respectively. The MTT, EdU and Colony formation assay were used to measure the effect of HYAL2 knockdown on glioma. The GSEA enrichment analysis was performed to explore the potential pathway regulated by HYAL2 in glioma, in addition, the HYAL2-regulated signaling pathways were detected by flow cytometry and Western blot. Finally, small molecule compounds targeting HYAL2 in glioma were screened by Cmap analysis. RESULTS: In the present study, we confirmed that Hyaluronidase 2 (HYAL2) is abnormally overexpressed in glioma. Moreover, we found that HYAL2 overexpression is associated with multiple glioma clinical traits and acts as a key indicator for glioma prognosis. Targeting HYAL2 could inhibit glioma progression by inducing glioma cell apoptosis and cell cycle arrest. CONCLUSION: Collectively, these observations suggest that HYAL2 overexpression could promote glioma progression. Thus, treatments that disrupt HA catabolism by altering HYAL2 expression may serve as effective strategies for glioma treatment.

Modified nodal stage of esophageal cancer based on the evaluation of the hazard rate of the negative and positive lymph node.

BACKGROUND: The study aimed to propose a modified N stage of esophageal cancer (EC) on the basis of the number of positive lymph node (PLN) and the number of negative lymph node (NLN) simultaneously. METHOD: Data from 13,491 patients with EC registered in the SEER database were reviewed. The parameters related to prognosis were investigated using a Cox proportional hazards regression model. A modified N stage was proposed based on the cut-off number of the re-adjusted ratio of the number of PLN (numberPLN) to the number of NLN (numberNLN), which were derived from the comparison of the hazard rate (HR) of numberPLN and numberNLN. The modified N stage was confirmed using the cross-validation method with the training and validation cohort, and it was also compared to the N stage from the American Joint Committee on Cancer (AJCC) staging system (7th edition) using Receiver Operating Characteristic (ROC) curve analysis. RESULTS: The numberPLN on prognosis was 1.042, while numberNLN was 0.968. The modified N stage was defined as follows: N1 stage: the ratio range was from 0 to 0.21; N2 stage: more than 0.21, but no more than 0.48; N3 stage: more than 0.48. The log-rank test indicated that significant survival differences were confirmed among the N1, N2 and N3 sub-groups of patients in the training population. The difference of all the patients using the modified N stage method were more significant than AJCC N stage. The result of ROC analysis indicated that the modified N stage could represent the N stage of EC more accurately. CONCLUSION: The modified N stage based on the re-adjusted ratio of numberPLN to numberNLN can evaluate tumor stage more accurately than the traditional N stage.

Diagnostic and Prognostic Potential of Serum Cell-Free microRNA-214 in Glioma.

OBJECTIVE: We aimed to expound feasibility of serum cell-free microRNA-214 (miR-214) as a noninvasive biomarker for glioma in this study. PATIENTS AND METHODS: We detected expression of miR-214 in medium from 2 glioma cell lines to confirm whether it is secretory in screening phase. Then, we verified cell-free miR-214 expression in serum samples from an independent set of 100 preoperative patients with glioma, 30 matching postoperative patients, and 100 healthy controls. RESULTS: MiR-214 was secreted from glioma cell lines. Extracellular miR-214 levels were significantly overexpressed in preoperative serum from glioma patients with glioma, whereas its expression significantly decreased in matched postoperative serum. Upregulated cell-free miR-214 in serum was significantly associated with higher tumor grade, absence of isocitrate dehydrogenase, and unmethylated methylguanine methyltransferase promoter. Extracellular miR-214 in serum could effectively distinguish patients with glioma from healthy control (area under the curve = 0.885; 95% confidence interval, 0.833-0.926). Moreover, serum cell-free miR-214 was an independent prognostic indicator of overall survival for patients with glioma. CONCLUSIONS: Serum cell-free miR-214 could serve as a promising noninvasive biomarker of glioma in tumor stratification, early diagnosis, and prognostic evaluation.