Bioinformatics Analysis Identifies PLA2G7 as a Key Antigen-Presenting Prognostic Related Gene Promoting Hepatocellular Carcinoma through the STAT1/PD-L1 Axis.

BACKGROUND: Antigen presentation may be an important factor contributing to immune evasion in cancer. This study investigated antigen-presenting prognostic related genes (APPGs) and their potential mechanisms in hepatocellular carcinoma (HCC). METHODS: We constructed a score built upon the core APPGs (APP.Score) through nonnegative matrix factorization (NMF) clustering, weighted gene co-expression network analysis (WGCNA), random forest (RF), and least absolute shrinkage and selection operator (LASSO) methods. We also compared the clinical and molecular characteristics of different APP.Score. Furthermore, in vitro experiments were conducted to validate the expression of core APPGs and investigate the effects of phospholipase A2, group 7 (PLA2G7) knockdown on HCC cell development and programmed death-ligand 1 (PD-L1) expression. RESULTS: APP.Score was positively correlated with immune cell infiltration and levels of immune checkpoint inhibitor-related genes, and negatively correlated with overall survival (OS). The area under the curve values were 0.734, 0.747, and 0.679 for survival periods of 1, 2, and 3 years, respectively, indicating that APP.Score could be an independent prognostic factor for patients with HCC. OS of the high expression group of these genes, including PLA2G7, musculin, heat shock protein family A, secreted phosphoprotein 1, and neutrophil cytosolic factor 2 (NCF2) was lower than that of their low expression group. Moreover, the upregulation of key components of APPGs, except NCF2, was observed in HCC. The inhibition of PLA2G7 suppressed HCC progression and reduced PD-L1 and phosphorylated signal transducer and activator of transcription 1 (p-STAT1)/STAT1 levels in HepG2 and Huh-7 cells. Remarkably, the decrease in PD-L1 expression caused by PLA2G7 silencing was reversed upon treatment with a STAT1 activator. CONCLUSION: The results of this study show that APP.Score could be an independent prognostic factor for patients with HCC, and that PLA2G7 silencing inhibits cancer cell development and PD-L1 expression. We provide a new perspective and potential target for immune research on antigen presentation in HCC.

Puntaje APP como predictor de mortalidad en pacientes con síndrome de dificultad respiratoria agudo grave por COVID-19 en un hospital referencial del norte del Perú / APP score as a predictor of mortality in patients with severe acute respiratory distress syndrome due to COVID-19 in a reference hospital in northern of Peru

INTRODUCCIÓN: La mortalidad por pacientes por COVID-19 grave que desarrollaban neumonía grave y síndrome de dificultad respiratoria agudo (SDRA) grave ha sido significativa a pesar del tratamiento oportuno. Es importante determinar predictores tempranos de enfermedad que nos ayuden a estratificar aquellos pacientes con mayor riesgo de fallecer. Se pretende estudiar el comportamiento del puntaje APP (APPS) como predictor de ello, basados en algunos reportes de uso y utilidad en el SDRA. no COVID-19. OBJETIVO: Determinar si el APPS es útil como predictor de mortalidad en SDRA. por COVID-19 grave. PACIENTES Y MÉTODO: Se realizó un estudio tipo cohorte retrospectivo, incluyendo pacientes de la Unidad de Cuidados Intensivos (UCI), con SDRA. por COVID-19 grave, que ingresaron a la UCI del Hospital Regional Docente de Trujillo (HRDT) en el período abril 2020- abril 2021. Se evalúo la utilidad del APPS como predictor de mortalidad em dicha población. RESULTADOS: El APPS demostró ser un factor asociado a mortalidad en pacientes con SDRA. y COVID-19 grave (RPa 1,34; IC 95% 1,16 a 1,56; p < 0,001). Además, encontramos que, al realizar un modelo de predicción ajustado por edad, sexo, SOFA, APPS, shock, Indice de Charlson (ICh), se comportan como factores asociados a mortalidad el APPS, el sexo masculino (RPa: 1,48; IC 95% 1,09 a 2,049; p < 0,05) y el ICh (RPa: 1,11; IC 95% 1,02 a 1,21; p < 0,05). CONCLUSIÓN: El APPS, el sexo masculino y el ICh son predictores de mortalidad en SDRA. por COVID-19 grave.

BACKGROUND: Mortality in patients with severe COVID-19 who developed severe pneumonia and severe Acute Respiratory Distress Syndrome (ARDS) has been significant despite timely treatment. It is important to determine early predictors of disease that help us to stratify those patients with a higher risk of death. It is intended to study the behavior of the APPS score as a predictor of this, based on some reports of use and usefulness in non-COVID-19 ARDS. AIM: To determine if the APP score is useful as a predictor of mortality in ARDS due to severe COVID-19. METHOD: A retrospective cohort study was carried out, including patients from the Intensive Care Unit (ICU) with ARDS due to severe COVID-19 who were admitted to the ICU of the Trujillo Regional Teaching Hospital (HRDT) in the period March 2020 to March 2021. The usefulness of the APP score as a predictor of mortality in mentioned population was evaluated. RESULTS: The APP score proved to be a factor associated with mortality in patients with ARDS and severe COVID-19 (APR 1.34; 95% CI 1.16 to 1.56; p < 0.001). We also found that when performing a prediction model adjusted for age, sex, SOFA, APP score, shock and Charlson Index (ICh) we found that the APP score, male sex (APR: 1.48; 95% CI 1.09 to 2.049; p < 0.05) and the ICh behave as factors associated with mortality (RPa: 1.11; 95% CI 1.02 to 1.21; p < 0.05). CONCLUSION: The APP score, male sex, and ICh are predictors of mortality in ARDS due to severe COVID-19.