Pan-cancer and single-cell analysis reveal THRAP3 as a prognostic and immunological biomarker for multiple cancer types.

Background: Thyroid hormone receptor-associated protein 3 (THRAP3) is of great significance in DNA damage response, pre-mRNA processing, and nuclear export. However, the biological activities of THRAP3 in pan-cancer remain unexplored. We aimed to conduct a comprehensive analysis of THRAP3 and validate its expression levels in lung cancer. Methods: A pan-cancer analysis was conducted to study the correlation of THRAP3 expression with clinical outcome and the tumor microenvironment based on the available bioinformatics databases. The protein levels of THRAP3 were explored in lung cancer by immunohistochemistry (IHC) analysis. Single-cell sequencing (ScRNA-seq) analysis was employed to investigate the proportions of each cell type in lung adenocarcinoma (LUAD) and adjacent normal tissues, along with the expression levels of THRAP3 within each cell type. Results: THRAP3 is upregulated in multiple cancer types but exhibits low expression in lung squamous cell carcinoma (LUSC). immunohistochemistry results showed that THRAP3 is a lowly expression in LUAD and LUSC. THRAP3 elevation had a poor prognosis in kidney renal clear cell carcinoma and a prolonged survival time in kidney chromophobe, brain lower-grade glioma and skin cutaneous melanoma, as indicated by the KM curve. Single-cell analysis confirmed that the proportions of T/B cells, macrophages, and fibroblasts were significantly elevated in LUAD tissues, and THRAP3 is specifically overexpressed in mast cells. Conclusion: Our findings uncover that THRAP3 is a promising prognostic biomarker and immunotherapeutic target in multiple cancers, but in LUAD and LUSC, it may be a protective gene.

The effectiveness of problem-based learning compared with lecture-based learning in surgical education: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis was conducted to systematically evaluate the impact of problem-based learning (PBL) and lecture-based learning (LBL) teaching models on students' learning in surgical education. METHODS: We systematically searched the publications related to the application of PBL and LBL in surgical courses in PubMed, Embase, Web of Science and Cochrane Library databases, the last retrieval time is September 20, 2022. After screening the literature according to the inclusion and exclusion criteria, extracting data and evaluating the methodological treatment of the included studies, Stata 17.0 software was used to perform meta-analysis. RESULTS: Nine studies were included totally. The results showed that compared with LBL, PBL was superior in clinical competence (SMD = 0.81, 95% CI: 0.12 ~ 1.49, P = 0.020) and student satisfaction (SMD = 2.13, 95% CI: 1.11 ~ 3.15, P < 0.0001) with significant differences. But the comprehensive scores (SMD = 0.26, 95% CI: -0.37 ~ 0.89, P = 0.421) and theoretical knowledge (SMD=-0.19, 95% CI: -0.71 ~ 0.33, P = 0.482) to PBL and LBL had no significant difference. CONCLUSION: This study showed that the PBL teaching model is more effective than the LBL teaching model in surgical education on the aspects of enhancing clinical competence and student satisfaction. However, further well-designed studies are needed to confirm our findings.

Association between CD8+ tumor-infiltrating lymphocytes and prognosis of non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitors: a systematic review and meta-analysis.

BACKGROUND: A meta-analysis method was used to investigate the prognostic value of CD8+ tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors. METHODS: A database search of PubMed, Embase, Web of Science and Cochrane Library up until 7 February, 2023. A clinical study on the relationship between CD8+ TILs and PD-1/PD-L1 inhibitors in the therapeutics of NSCLC. RevMan 5.3 and StataMP 17.0 software were used for meta-analysis. The outcome indicators incorporated overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). RESULTS: Nineteen articles with 1488 patients were included. The analysis results showed that high CD8+ TILs were associated with better OS (HR = 0.60, 95% CI: 0.46-0.77; P < 0.0001), PFS (HR = 0.68, 95% CI: 0.53-0.88; P = 0.003) and ORR (OR = 2.26, 95% CI: 1.52-3.36; P < 0.0001) in NSCLC patients treated with PD-1/PD-L1 inhibitors. Subgroup analysis indicated that patients with high CD8+ TILs had good clinical prognostic benefits whether the location of CD8+ TILs was intratumoral or stromal, and compared with East Asian, high CD8+ TILs in Caucasians showed a better prognosis. High CD8+ TILs in peripheral blood did not improve OS (HR = 0.83, 95% CI: 0.69-1.01; P = 0.06) and PFS (HR = 0.93, 95% CI: 0.61-1.14; P = 0.76) in NSCLC patients receiving PD-1/PD-L1 inhibitors. CONCLUSION: In spite of the location of CD8+ TILs, high densities of CD8+ TILs were predictive of treatment outcomes in NSCLC patients treated with PD-1/PD-L1 inhibitors. However, high CD8+ TILs in peripheral blood had no predictive effect.

Clinical and prognostic features of E-cadherin in adenocarcinoma of the esophagogastric junction patients.

OBJECTIVE: The expression, activity, and functional role of E-cadherin in adenocarcinoma of the esophagogastric junction (AEG) are unclear. In this research, we evaluated the expression of E-cadherin in AEG, as well as its clinicopathological significance and prognostic value. METHODS: A total of 65 AEG samples and 10 normal paracancerous tissues undergoing AEG resection in thoracic surgery were collected. The samples were immunohistochemically examined for expression levels of E-cadherin. The Chi-square test was used to determine if E-cadherin expression correlated with the clinicopathological features of AEG patients. The link between clinicopathological features and 5-year survival rates was investigated using Kaplan-Meier survival curves and multifactorial Cox regression analysis. RESULTS: In AEG tissues, E-cadherin expression was considerably reduced. Differentiation grade ( P = 0.013), infiltration depth ( P = 0.033), and clinicopathological stage ( P = 0.045) were substantially linked to the level of E-cadherin expression. Five-year survival rates of AEG patients were affected by E-cadherin expression ( P = 0.037), tumor differentiation ( P = 0.010), lymph node metastasis ( P < 0.001), and clinicopathological stage ( P = 0.037). Tumor differentiation ( P = 0.033) and lymph node metastasis ( P = 0.001) were independent risk factors for shorter overall survival. CONCLUSION: E-cadherin expression in AEG was significantly decreased, which was strongly related to tumor differentiation, infiltration, and clinicopathological stage. An E-cadherin deficiency would lead to poor prognosis in AEG patients. E-cadherin may play a crucial role in AEG invasion and metastasis. Low expression of E-cadherin may be a potential early biomarker and overall survival predictor for AEG patients.

The molecular mechanism of METTL3 promoting the malignant progression of lung cancer.

Lung cancer remains one of the major causes of cancer-related death globally. Recent studies have shown that aberrant m6A levels caused by METTL3 are involved in the malignant progression of various tumors, including lung cancer. The m6A modification, the most abundant RNA chemical modification, regulates RNA stabilization, splicing, translation, decay, and nuclear export. The methyltransferase complex plays a key role in the occurrence and development of many tumors by installing m6A modification. In this complex, METTL3 is the first identified methyltransferase, which is also the major catalytic enzyme. Recent findings have revealed that METTL3 is remarkably associated with different aspects of lung cancer progression, influencing the prognosis of patients. In this review, we will focus on the underlying mechanism of METT3 in lung cancer and predict the future work and potential clinical application of targeting METTL3 for lung cancer therapy.