Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Is a Promising Signature to Predict Prognosis and Therapies for Hepatocellular Carcinoma (HCC).

BACKGROUND: The roles of mitochondria and the endoplasmic reticulum (ER) in the progression of hepatocellular carcinoma (HCC) are well established. However, a special domain that regulates the close contact between the ER and mitochondria, known as the mitochondria-associated endoplasmic reticulum membrane (MAM), has not yet been investigated in detail in HCC. METHODS: The TCGA-LIHC dataset was only used as a training set. In addition, the ICGC and several GEO datasets were used for validation. Consensus clustering was applied to test the prognostic value of the MAM-associated genes. Then, the MAM score was constructed using the lasso algorithm. In addition, uncertainty of clustering in single-cell RNA-seq data using a gene co-expression network (AUCell) was used for the detection of the MAM scores in various cell types. Then, CellChat analysis was applied for comparing the interaction strength between the different MAM score groups. Further, the tumor microenvironment score (TME score) was calculated to compare the prognostic values, the correlation with the other HCC subtypes, tumor immune infiltration landscape, genomic mutations, and copy number variations (CNV) of different subgroups. Finally, the response to immune therapy and sensitivity to chemotherapy were also determined. RESULTS: First, it was observed that the MAM-associated genes could differentiate the survival rates of HCC. Then, the MAM score was constructed and validated using the TCGA and ICGC datasets, respectively. The AUCell analysis indicated that the MAM score was higher in the malignant cells. In addition, enrichment analysis demonstrated that malignant cells with a high MAM score were positively correlated with energy metabolism pathways. Furthermore, the CellChat analysis indicated that the interaction strength was reinforced between the high-MAM-score malignant cells and T cells. Finally, the TME score was constructed, which demonstrated that the HCC patients with high MAM scores/low TME scores tend to have a worse prognosis and high frequency of genomic mutations, while those with low MAM scores/high TME scores were more likely to have a better response to immune therapy. CONCLUSIONS: MAM score is a promising index for determining the need for chemotherapy, which reflects the energy metabolic pathways. A combination of the MAM score and TME score could be a better indicator to predict prognosis and response to immune therapy.

Gamma-Glutamyltransferase Elevation Is Frequent in Patients With COVID-19: A Clinical Epidemiologic Study.

A newly identified coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the infectious coronavirus disease 2019 (COVID-19), emerged in December 2019 in Wuhan, Hubei Province, China, and now poses a major threat to global public health. Previous studies have observed highly variable alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in patients with COVID-19. However, circulating levels of the cholangiocyte injury biomarker gamma-glutamyltransferase (GGT) have yet to be reported in the existing COVID-19 case studies. Herein, we describe the relationship between GGT levels and clinical and biochemical characteristics of patients with COVID-19. Our study is a retrospective case series of 98 consecutive hospitalized patients with confirmed COVID-19 at Wenzhou Central Hospital in Wenzhou, China, from January 17 to February 5, 2020. Clinical data were collected using a standardized case report form. Diagnosis of COVID-19 was assessed by symptomatology, reverse-transcription polymerase chain reaction (RT-PCR), and computed tomography scan. The medical records of patients were analyzed by the research team. Of the 98 patients evaluated, elevated GGT levels were observed in 32.7%; increased C-reactive protein (CRP) and elevated ALT and AST levels were observed in 22.5%, 13.3%, and 20.4%, respectively; and elevated alkaline phosphatase (ALP) and triglycerides (TGs) were found in 2% and 21.4%, respectively. Initially, in the 82 patients without chronic liver disease and alcohol history, age older than 40 years (P = 0.027); male sex (P = 0.0145); elevated CRP (P = 0.0366), ALT (P < 0.0001), and ALP (P = 0.0003); and increased TGs (P = 0.0002) were found to be associated with elevated GGT levels. Elevated GGT (P = 0.0086) and CRP (P = 0.0162) levels had a longer length of hospital stay. Conclusion: A sizable number of patients with COVID-19 infection have elevated serum GGT levels. This elevation supports involvement of the liver in persons with COVID-19.