Exosomal MALAT1 promotes the proliferation of esophageal squamous cell carcinoma through glyoxalase 1-dependent methylglyoxal removal.

In previous study we characterized the oncogenic role of long non-coding RNA MALAT1 in esophageal squamous cell carcinoma (ESCC), but the detailed mechanism remains obscure. Here we identified glyoxalase 1 (GLO1) as the most possible executor of MALAT1 by microarray screening. GLO1 is responsible for degradation of cytotoxic methylglyoxal (MGO), which is by-product of tumor glycolysis. Accumulated MGO may lead to glycation of DNA and protein, resulting in elevated advanced glycation end products (AGEs), while glyoxalase 1 detoxify MGO to alleviate its cytotoxic effect to tumor cells. GLO1 interfering led to accumulation of AGEs and following activation of DNA injury biomarkers, which lead to cell cycle arrest and growth inhibition. In silico analysis based on online database revealed abundant enrichment of histone acetylation marker H3K27ac in GLO1 promotor, and acetyltransferase inhibitor C646 declined GLO1 expression. Acetyltransferase KAT2B, which was also identified as a target of MALAT, mediated histone lysine acetylation of GLO1 promotor, which was confirmed by ChIP-qPCR experiment. Shared binding sites of miR-206 were found on MALAT1 and KAT2B mRNA. Dual-luciferase reporter assays confirmed interaction within MALAT1-miR-206-GLO1. Finally, we identified MALAT1 encapsuled by exosome from donor cells, and transferred malignant behaviors to recipient cells. The secreted exosomes may enter circulation, and serum MALAT1 level combined with traditional tumor markers showed potential power for ESCC diagnosis.

Effect of early enteral nutrition on short-term outcomes and survival in patients in the cardiothoracic intensive care unit: An inverse probability weighted retrospective study.

OBJECTIVES: The merits of early enteral nutrition (EEN) in patients in the cardiothoracic intensive care unit (CTICU) remain unclear. This retrospective study aimed to address this issue. METHODS: We analyzed data from the MIMIC IV v2.0 database, including patients with a CTICU stay of ≥4 d. Patients were divided into early and delayed enteral nutrition (EN) groups. Differences in baseline data were corrected using an inverse probability weighting (IPW) approach. Generalized linear models (GLMs) were used to compare trends over time between groups, and survival effects were evaluated with weighted logistic and Cox regression, supplemented by weighted Kaplan-Meier curves. Subgroup analysis facilitated the exploration of potential interactions. RESULTS: The study included 720 CTICU patients. Following IPW, all baseline variables were balanced. EEN led to shorter hospital and CTICU stays, lower incidence of respiratory and blood infections, and reduced total insulin usage in the first week of CTICU admission, albeit with an increased total gastric residual volume. Mortality risk between the groups did not significantly differ at 28 d or at 1 y. Excessive early energy and protein intake elevated the risk of 28-d mortality, but the relationship may not be linear. Overweight patients or those with fewer comorbidities had a higher mortality risk with EEN. CONCLUSIONS: EEN may improve short-term outcomes in CTICU patients without a clear survival benefit. Early high caloric and protein intake could lead to adverse outcomes, suggesting a careful evaluation for initiating EN in specific patients.

Role of surgery in T4N0-3M0 esophageal cancer.

BACKGROUND: This study aimed to investigate an unsettled issue that whether T4 esophageal cancer could benefit from surgery. METHODS: Patients with T4N0-3M0 esophageal cancer from 2004 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. Kaplan-Meier method, Cox proportional hazard regression, and propensity score matching (PSM) were used to compare overall survival (OS) between the surgery and no-surgery group. RESULTS: A total of 1822 patients were analyzed. The multivariable Cox regression showed the HR (95% CI) for surgery vs. no surgery was 0.492 (0.427-0.567) (P < 0.001) in T4N0-3M0 cohort, 0.471 (0.354-0.627) (P < 0.001) in T4aN0-3M0 cohort, and 0.480 (0.335-0.689) (P < 0.001) in T4bN0-3M0 cohort. The HR (95% CI) for neoadjuvant therapy plus surgery vs. no surgery and surgery without neoadjuvant therapy vs. no surgery were 0.548 (0.461-0.650) (P < 0.001) and 0.464 (0.375-0.574) (P < 0.001), respectively. No significant OS difference was observed between neoadjuvant therapy plus surgery and surgery without neoadjuvant therapy: 0.966 (0.686-1.360) (P = 0.843). Subgroup analyses and PSM-adjusted analyses showed consistent results. CONCLUSION: Surgery might bring OS improvement for T4N0-3M0 esophageal cancer patients, no matter in T4a disease or in T4b disease. Surgery with and without neoadjuvant therapy might both achieve better OS than no surgery.

The Prognostic Value of Postoperative Radiotherapy for Thymoma and Thymic Carcinoma: A Propensity-Matched Study Based on SEER Database.

(1) Objectives: The effect of postoperative radiotherapy (PORT) for thymoma and thymic carcinoma remains controversial. This study aimed to investigate the prognostic value of PORT for thymoma and thymic carcinoma in a population-based registry. (2) Methods: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with thymoma and thymic carcinoma between 2010 and 2019. Propensity score matching was performed to adjust statistical influences between the PORT and non-PORT groups. (3) Results: A total of 2558 patients with thymoma (n = 2138) or thymic carcinoma (n = 420) were included. In the multivariate analysis, PORT was an independent prognostic factor for OS (overall survival; p < 0.001) and CSS (cancer-specific survival; p = 0.001) in thymoma and an independent prognostic factor for OS in thymic carcinoma (p = 0.018). Subgroup analyses revealed that PORT was beneficial to OS and CSS in patients with Masaoka-Koga stage IIB-IV thymoma (OS: IIB, p < 0.001; III-IV, p = 0.005; CSS: IIB, p = 0.015; III-IV, p = 0.002) and stage IIB thymic carcinoma (OS: p = 0.012; CSS: p = 0.029). (4) Conclusion: This propensity-matched analysis identified the prognostic value of PORT in thymoma and thymic carcinoma based on the SEER database. For patients with stage IIB-IV thymoma and stage IIB thymic carcinoma, PORT was associated with improved OS and CSS. A more positive attitude towards the use of PORT for nonlocalized thymoma and thymic carcinoma may be appropriate.

Prognostic significance of tumor regression grade in esophageal squamous cell carcinoma after neoadjuvant chemoradiation.

Backgrounds: Trimodal therapy (neoadjuvant chemoradiotherapy followed by esophagectomy) for locally advanced esophageal squamous cell carcinoma (ESCC) is associated with a significant survival benefit. Modified Ryan score is an effective tool to evaluated the tumor regression grade (TRG) after neoadjuvant therapy. The aim of this study was to evaluate the prognostic value of TRG for overall survival (OS) and disease-free survival (DFS) in ESCC patients undergoing neoadjuvant chemoradiation. Methods: The study retrospectively reviewed 523 ESCC patients who underwent neoadjuvant chemoradiotherapy and radical esophagectomy at Jinling Hospital from January 2014 to July 2020. Kaplan-Meier curves with log-rank test and Cox regression model were used to evaluate the prognostic factor of TRG based on modified Ryan scoring system on OS and DFS. Results: After application of inclusion and exclusion criteria, 494 patients with ESCC following neoadjuvant chemoradiotherapy and radical esophagectomy were available for analysis. The TRG scores are significantly associated with smoke history (p = 0.02), lymphovascular invasion (LVI) and/or peripheral nerve invasion (PNI) (p < 0.01), and postoperative adjuvant therapy (p < 0.01). Meanwhile, tumor characteristics including tumor length (p < 0.01) and tumor differentiation grade (p < 0.01) are also significantly associated with TRG score. The results of multivariable Cox regression modal showed that TRG is not an independently prognostic factor for OS (p = 0.922) or DFS (p = 0.526) but tumor length is an independently prognostic factor for DFS (p = 0.046). Conclusions: This study evaluated the prognostic value of modified Ryan scoring system for ESCC after trimodal therapy and concluded that modified Ryan scoring system can predict survival and recurrence rates but is not an independently prognostic factor for OS and DFS.