[Clinicopathological analysis of gastric adenocarcinoma with elevated serum alpha-fetoprotein and enteroblastic differentiation].

Objective: To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED). Methods: The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis. Results: Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177-GNAS, AIM1-FGFR3, and EPHA6-ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis (P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone (P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone (P＜0.05). Conclusions: Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

Knockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis.

The article "Knockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis, by B.-G. Tian, Z. Hua, Z.-J. Wang, J. Li, published in Eur Rev Med Pharmacol Sci 2020; 24 (3): 1030-1040-DOI: 10.26355/eurrev_202002_20153-PMID: 32096182" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20153.

Knockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis.

OBJECTIVE: This study aimed to investigate the physiological function and molecular mechanism of microRNA-181a (miRNA-181a) in the carcinogenesis of osteosarcoma. MATERIALS AND METHODS: The relative expression of miRNA-181a in tissues and cultured cells was detected by quantitative real time-polymerase chain reaction (qRT-PCR). MiR-181a inhibitor and miR-181a mimics were used to manipulate its level in cells. Cell proliferation and invasion were measured using Cell Counting Kit-8 (CCK-8) assay and transwell assay, respectively. The protein levels of the targeted genes were detected by Western blotting and immunohistochemistry. Terminal Deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) assay was employed to detect cell apoptosis. Moreover, a xenograft tumor bearing mice model was used to evaluate the effect of miR-181a in vivo. RESULTS: We found that miRNA-181a was aberrantly elevated in osteosarcoma tissues and cells. Moreover, the overexpression of miRNA-181a could facilitate cell proliferation and migration. By contrast, miRNA-181a knockdown reverses these effects. Additionally, downregulation of miRNA-181a could activate NOD-like receptor protein 3 (NLRP3)-dependent pyroptosis, as evidenced by the increase of pyroptosis-related genes (NLRP3, caspase-1, interleukin-18, and interleukin-1ß) in miRNA-181a inhibitor transfected cells compared with the control. Further mechanistic studies identified that miRNA-181a knockdown suppresses cell proliferation and invasion by activating NLRP3-dependent pyroptosis. Silencing NLRP3 could effectively reverse the effects mediated by miRNA-181a inhibitor. Consistently, in vitro results also demonstrated that blockade of miRNA-181a notably suppresses tumor growth via activating pyroptosis. CONCLUSIONS: These results provide that miRNA-181a might serve as potential therapeutic target for osteosarcoma patients.