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Cell Death Dis ; 13(2): 176, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35210426


Microvascular invasion (MVI) is presently evaluated as a high-risk factor to be directly relative to postoperative prognosis of hepatocellular carcinoma (HCC). Up to now, diagnosis of MVI mainly depends on the postoperative pathological analyses with H&E staining assay, based on numbers and distribution characteristics of MVI to classify the risk levels of MVI. However, such pathological analyses lack the specificity to discriminate MVI in HCC specimens, especially in complicated pathological tissues. In addition, the efficiency to precisely define stages of MVI is not satisfied. Thus, any biomarker for both conforming diagnosis of MVI and staging its levels will efficiently and effectively promote the prediction of early postoperative recurrence and metastasis for HCC. Through bioinformatics analysis and clinical sample verification, we discovered that Stathmin 1 (STMN1) gene was significantly up-regulated at the locations of MVI. Combining STMN1 immunostaining with classic H&E staining assays, we established a new protocol for MVI pathological diagnosis. Next, we found that the degrees of MVI risk could be graded according to expression levels of STMN1 for prognosis prediction on recurrence rates and overall survival in early HCC patients. STMN1 affected epithelial-mesenchymal transformation (EMT) of HCC cells by regulating the dynamic balance of microtubules through signaling of "STMN1-Microtubule-EMT" axis. Inhibition of STMN1 expression in HCC cells reduced their lung metastatic ability in recipients of mouse model, suggesting that STMN1 also could be a potential therapeutic target for inhibiting HCC metastasis. Therefore, we conclude that STMN1 has potentials for clinical applications as a biomarker for both pathological diagnosis and prognostic prediction, as well as a therapeutic target for HCC.

Carcinoma Hepatocelular , Neoplasias Hepáticas , Estatmina , Animais , Biomarcadores , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Camundongos , Invasividade Neoplásica , Estudos Retrospectivos , Estatmina/genética
Medicine (Baltimore) ; 101(2): e28544, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029212


RATIONALE: Postmortem imaging (PMI), including computed tomography (PMCT), postmortem computed tomography angiography (PMCTA), and postmortem magnetic resonance imaging (PMMRI), is rapidly becoming effective and a practical method in forensic medicine. This study aimed to present a specific forensic case in which the PMI approach and its applications were used. PATIENT CONCERNS: A 40-year-old male patient had moderate unilateral nose bleeding constantly 10 times after suffering from a head injury induced by a car accident. After a bilateral massive nose bleeding for the last time, he died from hemorrhagic shock. Traumatic internal carotid artery pseudoaneurysm (TICAP) was suspected in this patient. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: A whole-body scanning was performed using PMCT and PMMRI. Then, PMCTA using left ventricular cardiac puncture was also implemented. A water-soluble contrast agent was injected into the left ventricle and pumped toward the intracranial, followed by a repeated whole-body PMCT scan. The PMCT/PMMRI detected a high-density/signal mass inside the left sphenoid sinus. The PMCTA detected a distinct leakage of the contrast agent into the left sphenoid sinus from an adjacent aneurysm of the C3 section of the left internal carotid artery. Autopsy and histology confirmed a TICAP inside the sphenoid sinus. LESSONS: This case showed that the PMI was of great value for identifying the cause of death in special cases. When vascular lesions are suspected in the body, PMI and especially the PMCTA approach may be an effective detection method.

Falso Aneurisma/diagnóstico por imagem , Autopsia/métodos , Artéria Carótida Interna/diagnóstico por imagem , Meios de Contraste , Adulto , Falso Aneurisma/etiologia , Angiografia por Tomografia Computadorizada , Evolução Fatal , Hemorragia , Humanos , Masculino
Front Oncol ; 11: 736694, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692512


Pancreatic adenocarcinoma is one of the most lethal diseases with a 5-year survival rate of about 8%. ASXL2 is an epigenetic regulator associated with various tumors including colorectal cancer, breast cancer, and myeloid leukemia. However, the role of ASXL2 in pancreatic cancer remains unclear. This is the first research focusing on the prognostic value of ASXL2 in pancreatic cancer. In this research, we aimed to explore the correlation between ASXL2 and the prognosis, as well as other features in PAAD. We obtained gene expression profiles of PAAD and normal tissues from TCGA, GEO, and Xena databases. TIMER and CIBERSORT algorithms were employed to investigate the effect of ASXL2 on tumor microenvironment. GSEA along with GO and KEGG enrichment analyses were conducted to uncover the biological functions of ASXL2. The response to various chemotherapeutic drugs was estimated by algorithms in R package "pRRophetic", while the sensitivity to immunotherapy was quantified by TIDE score. We found that ASXL2 was upregulated in the PAAD samples and elevated expression of ASXL2 was linked to poor overall survival. ASXL2 DNA methylation contributed to ASXL2 expression. Functional annotation indicated that ASXL2 was mainly involved in inflammatory response and epithelial mesenchymal transition. Patients with high ASXL2 expression were more likely to benefit from immune checkpoint blockade, gemcitabine, and mitomycin-C. Finally, external datasets and biospecimens were used and the results further validated the aberrant expression of ASXL2 in PAAD samples. In summary, our results highlight that ASXL2 is a potential prognostic and predictive biomarker in pancreatic cancer.