[Clinical characteristics and prognosis analysis of 17 cases of SMARCA4-deficient chest tumors].

Objective: To analyze the clinical characteristics and prognosis of 17 patients with pathologically confirmed SMARCA4-deficient chest tumors. Methods: Seventeen patients with SMARCA4-deficient thoracic tumors diagnosed by pathology in the Affiliated Hospital of Jining Medical University from September 2021 to January 2023 were collected through Results Query System of Pathology Department, and the patients' general conditions, clinical symptoms, tumor markers, imaging features, treatment and regression were retrospectively analyzed, and literature review was performed. Results: A total of 17 patients were included in this study. Their clinical characteristics were characterized as follows: male/female=16/1, age 42-74 years, mean (64.0±5.7)years. Only 1 female had no clear smoking history, and 16 males had a smoking history, of whom 1 had 5 smoking pack-years, and the remaining 15 case had a smoking history of 20-100 smoking pack-years, with a mean of (68.5±44.5) smoking pack-years. Clinical symptoms were mainly cough and sputum, followed by chest tightness, hemoptysis and chest pain. Tumor markers CYFRA19-9 was elevated in 9 cases (3.79-16.61 ng/ml), CEA was elevated in 8 cases (5.37-295.93 ng/ml), and NSE was elevated in 6 cases (17.18-70.37 ng/ml). Imaging manifestations were intrapulmonary or mediastinal mass shadows, and the tumor involved the mediastinum in 9 cases, the upper lobe of the right lung in 6 cases, the upper lobe of the left lung in 5 cases, the lower lobe of the right lung in 3 cases, the lower lobe of the left lung in 3 cases; cervical or supraclavicular lymph node metastasis in 8 cases, pleural metastasis in 4 cases, hepatic metastasis in 3 cases, cerebral metastasis in 3 cases, bone metastasis in 2 cases, and subcutaneous metastasis in 1 case. Combining immuno-histochemistry and pathology, there were 6 cases of SMARCA4-deficient NSCLC and 11 cases of SMARCA4-deficient undifferentiated tumor. Eight patients were treated with platinum-contained chemotherapy agents, four of which were combined with immune checkpoint inhibitors, and one was treated with enzatinib; only one of the 9 patients achieved partial remission after treatment, and the remaining eight had progression of the tumors on chest CT after treatment. Five patients abandoned the treatment, and died in 6-month of follow-up. Three patients underwent surgery for resection, and there was no significant progression in the three patients in the 6 months of follow-up. Conclusions: Clinically, middle-aged and elderly men with a history of heavy smoking should be given high priority, especially in patients whose imaging mostly showed intrapulmonary, especially in upper lobes, and/or mediastinal masses, rapid lesion progression, and early distant metastasis, and who should be alerted to the possibility of SMARCA4-deficient thoracic tumors. Late clinical stage is a high risk factor for poor overall patient survival, and platinum-containing chemotherapy agents combined with immune checkpoint inhibitor therapy may be effective, and early surgery may improve patient prognosis.

Associations of Toll-like receptor 3 gene single nucleotide polymorphisms with cataract.

OBJECTIVE: The aim of this study was to investigate the expression of Toll-like receptor 3 (TLR3) gene in the anterior capsule of cataract patients and to explore the correlations of its polymorphisms with the incidence of cataract. PATIENTS AND METHODS: A total of 80 cataract patients (Cataract group) and 38 clear lenses (Control group) were selected as research subjects. Western blotting assay was used to detect the protein expression of TLR3 in Cataract group and Control group. Subsequently, single nucleotide polymorphisms (SNPs) rs128912, rs100321 and rs129103 in the promoter region of TLR3 gene were classified by conformation-difference gel electrophoresis. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to test the correlations of different gene polymorphisms with the protein expression of TLR3. Meanwhile, chi-square test was applied to check whether the distribution frequency of TLR3 genotypes conforms to the Hardy-Weinberg genetic equilibrium law. Furthermore, the associations of alleles and gene polymorphisms of TLR3 with the incidence of cataract were analyzed. RESULTS: Western blotting results found that the protein expression level of TLR3 in the anterior capsule in Cataract group was significantly higher than that in Control group (p<0.05). Hardy-Weinberg genetic equilibrium analysis showed that three TLR3 gene polymorphisms conformed to the genetic equilibrium distribution (p>0.05). Subsequent results demonstrated that the protein expression level of TLR3 in cataract patients with genotype TT of TLR3 gene polymorphism rs128912 was remarkably higher than that in patients with genotypes AA and AT (p<0.05). Moreover, the results of genetic association analysis manifested that only gene polymorphism rs128912 and its alleles were associated with cataract (p<0.05). However, gene polymorphisms rs100321 and rs129103 and their alleles were not correlated with the incidence of cataract (p>0.05). CONCLUSIONS: TLR3 was highly expressed in the anterior capsule of patients with cataract. In addition, rs128912 in the promoter region of TLR3 gene was correlated with the incidence of cataract, while rs100321 and rs129103 were not associated with the incidence of cataract.

MicroRNA-16 inhibits the proliferation, migration and invasion of non-small cell lung carcinoma cells by down-regulating matrix metalloproteinase-19 expression.

OBJECTIVE: This study aims to investigate the expression of microRNA (miR)-16 in non-small cell lung carcinoma (NSCLC) and to identify its potential mechanism. PATIENTS AND METHODS: A total of 45 NSCLC patients were included in the present work. NSCLC tissues and adjacent normal tissues were resected and collected. The Reverse Transcription-quantitative Polymerase Chain Reaction was used to determine miR-16 expression. Regulatory effects of miR-16 on proliferation, migration and invasion, and cell cycle of A549 cells were determined by Cell-Counting Kit 8 assay, transwell assay, and flow cytometry, respectively. Western blotting was performed to measure the protein expression of matrix metalloproteinase (MMP)-19 in cells overexpressing miR-16. Dual-luciferase reporter gene assay was conducted to identify the interaction between miR-16 and MMP-19. RESULTS: MiR-16 expression in NSCLC significantly decreased compared with that in healthy tissue (p<0.05). The expression level of miR-16 was negatively correlated to the clinical staging of NSCLC. In addition, the expression of miR-16 in NSCLC patients with lymph node metastasis was significantly lower than that in patients without lymph node metastasis (p<0.05). In vitro studies demonstrated that miR-16 inhibited the proliferation, migration, and invasion of A549 cells. Western blotting analyses indicated that overexpression of miR-16 down-regulated the expression of MMP-19. Additionally, the dual-luciferase reporter gene assay determined that miR-16 directly regulated the expression of MMP-16. CONCLUSIONS: The present study demonstrates that miR-16 acts as a tumor-suppressor gene by inhibiting the proliferation, migration, and invasion of NSCLC cells via downregulating MMP-19 expression.