CDH1

BACKGROUND: Nodular gastritis (NG) is characterized by marked antral lymphoid follicle formation, and is a strong risk factor for diffuse-type gastric cancer in adults. However, it is unknown whether aberrant DNA methylation, which is induced by atrophic gastritis (AG) and is a risk for gastric cancer, is induced by NG. Here, we analyzed methylation induction by NG. METHODS: Gastric mucosal samples were obtained from non-cancerous antral tissues of 16 NG and 20 AG patients with gastric cancer and 5 NG and 6 AG patients without, all age- and gender-matched...

PURPOSE: To investigate the transcriptome of human bronchial epithelial cells (HBEC) in response to serum from patients with different degrees of inflammation. METHODS: Serum from 19 COVID-19 patients obtained from the Hannover Unified Biobank was used. At the time of sampling, 5 patients had a WHO Clinical Progression Scale (WHO-CPS) score of 9 (severe illness). The remaining 14 patients had a WHO-CPS of below 9 (range 1-7), and lower illness. Multiplex immunoassay was used to assess serum inflammatory markers...

Emerging studies have demonstrated the link between RNA modifications and various cancers, while the predictive value and functional mechanisms of RNA modification-related genes (RMGs) in esophageal squamous cell carcinoma (ESCC) remain unclear. Here we established a prognostic signature for ESCC based on five RMGs. The analysis of ESCC clinical samples further verified the prognostic power of the prognostic signature. Moreover, we found that the knockdown of NSUN6 promotes ESCC progression in vitro and in vivo , whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells...

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Careful microscopic observation of histopathological specimens, accumulation of large numbers of high-quality tissue specimens, and analysis of molecular pathology in relation to morphological features are considered to yield realistic data on the nature of multistage carcinogenesis. Since the morphological hallmark of cancer is disruption of the normal histological structure maintained through cell-cell adhesiveness and cellular polarity, attempts have been made to investigate abnormalities of the cadherin-catenin cell adhesion system in human cancer cells...

BACKGROUND: Drug resistance in endometrial cancer (EC) is a serious problem and a barrier to improving prognosis. The PI3K/AKT/mTOR pathway is highly activated in EC and can serve as a potential therapeutic target. Inhibitors against AKT have been developed, but resistance to these inhibitors is a concern. This study aimed to establish AKT inhibitor resistant cell lines and identify differentially expressed genes (DEGs) between parental and AKT inhibitor resistant cell lines to understand the mechanism of drug resistance to AKT inhibitors in EC...

We performed the next-generation sequencing (NGS) analysis of a rare grade 1 brain meningioma (angiomatous type) and a common grade 1 spinal meningioma (psammomatous type) and compared their mutation profiling. The data were analysed using the Ion Reporter 5.16 programme (Thermo Fisher Scientific, Waltham, MA). Sequencing analysis identified 10 novel variants and two previously reported variants that were common between these two tumours. Nine variants were missense, which included an insertion in EGFR c.1819_1820insCA, causing frameshifting, and a single nucleotide deletion in HRAS and HNF1A genes, causing frameshifting in these genes...

BACKGROUND: Drug induced bile duct injury is a frequently observed clinical problem leading to a wide range of pathological features. During the past decades, several agents have been identified with various postulated mechanisms of bile duct damage, however, mostly still poorly understood. METHODS: Here, we investigated the mechanisms of chlorpromazine (CPZ) induced bile duct injury using advanced in vitro cholangiocyte cultures. Intrahepatic cholangiocyte organoids (ICOs) were driven into mature cholangiocyte like cells (CLCs), which were exposed to CPZ under cholestatic or non-cholestatic conditions through the addition of a bile acid cocktail...

In this editorial we comment on an article published in a recent issue of the World J Gastrointest Surg . A common gene mutation in gastric cancer (GC) is the TP53 mutation. As a tumor suppressor gene, TP53 is implicated in more than half of all tumor occurrences. TP53 gene mutations in GC tissue may be related with clinical pathological aspects. The TP53 mutation arose late in the progression of GC and aided in the final switch to malignancy. CDH1 encodes E-cadherin, which is involved in cell-to-cell adhesion, epithelial structure maintenance, cell polarity, differentiation, and intracellular signaling pathway modulation...

OBJECTIVE: There is an ongoing debate about whether the management of gastroenteropancreatic (GEP) neuroendocrine carcinoma (NEC) should follow the guidelines of small-cell lung cancer (SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart. METHODS: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing (NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC (LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes...

BACKGROUND: Breast Cancer (BC) is a highly heterogeneous and complex disease. Personalized treatment options require the integration of multi-omic data and consideration of phenotypic variability. Radiogenomics aims to merge medical images with genomic measurements but encounter challenges due to unpaired data consisting of imaging, genomic, or clinical outcome data. In this study, we propose the utilization of a well-trained conditional generative adversarial network (cGAN) to address the unpaired data issue in radiogenomic analysis of BC...

Diffuse-type gastric adenocarcinoma (DGAC) is a deadly cancer often diagnosed late and resistant to treatment. While hereditary DGAC is linked to CDH1 mutations, the role of CDH1/E-cadherin inactivation in sporadic DGAC tumorigenesis remains elusive. We discovered CDH1 inactivation in a subset of DGAC patient tumors. Analyzing single-cell transcriptomes in malignant ascites, we identified two DGAC subtypes: DGAC1 (CDH1 loss) and DGAC2 (lacking immune response). DGAC1 displayed distinct molecular signatures, activated DGAC-related pathways, and an abundance of exhausted T cells in ascites...

INTRODUCTION: Abnormal alternative splicing (AS) contributes to aggressive intrahepatic invasion and metastatic spread, leading to the high lethality of hepatocellular carcinoma (HCC). OBJECTIVES: This study aims to investigate the functional implications of UPF3B-S (a truncated oncogenic splice variant) in HCC metastasis. METHODS: Basescope assay was performed to analyze the expression of UPF3B-S mRNA in tissues and cells. RNA immunoprecipitation, and in vitro and in vivo models were used to explore the role of UPF3B-S and the underlying mechanisms...

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of heart failure cases. The molecular mechanisms by which HFpEF leads to impaired diastolic function of the heart have not been clarified, nor have the drugs that target the clinical symptoms of HFpEF patients. METHODS: HFpEF chip data (GSE180065) was downloaded from the National Center for Biotechnology Information (NCBI) database. Differentially expressed genes (DEGs) were filtered by the limma package in R and processed for GO and KEGG pathway analyses...

The goal of a gastric cancer operation is a microscopically negative resection margin and D2 lymphadenectomy. Minimally invasive techniques (laparoscopic and robotic) have been proven to be equivalent for oncologic care, yet with faster recovery. Endoscopic mucosal resection can be used for T1a N0 tumor resection. Better understanding of hereditary gastric cancer and molecular subtypes has led to specialized recommendations for MSI-high tumors and patients with pathogenic CDH1 mutations. In the future, surgical management will support minimally invasive approaches and personalized cancer care based on subtype...

O-linked-β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) and ubiquitination are critical posttranslational modifications that regulate tumor development and progression. The continuous progression of the cell cycle is the fundamental cause of tumor proliferation. S-phase kinase-associated protein 2 (SKP2), an important E3 ubiquitin ligase, assumes a pivotal function in the regulation of the cell cycle. However, it is still unclear whether SKP2 is an effector of O-GlcNAcylation that affects tumor progression...

BACKGROUND: Individual patients with ovarian cancer show remarkably different prognosis. Present prognostic models for ovarian cancer mainly focus on clinico-pathological parameters, so quantifiable prognostic markers at molecular level are urgently needed. Platelets contribute to ovarian cancer progression, but have not been considered as biomarkers likely due to their instability. Here, we aimed to search for a stable prognostic marker from platelet-treated ovarian cancer cells, and explore its functions and mechanisms...

INTRODUCTION: Gastric cancer is one of the top 5 cancers worldwide. Most gastric cancers are classified as sporadic with the exception of around 3 % that are associated with specific syndromes or genes. Hereditary diffuse gastric cancer is a very rare type of gastric cancer, associated with loss of function of a tumor suppressor gene CDH1 which has a high penetrance that can reach 90 % over a lifetime. CASE PRESENTATION: Here we present the case of a 31 years old male patient carrying the CDH1 gene who presented for prophylactic total gastrectomy and D1 lymphadenectomy followed by a roux en y esophago-jejunostomy for digestive tract reconstruction...

Exploring the mechanism of self-renewal and pluripotency maintenance of human embryonic stem cells (hESCs) is of great significance in basic research and clinical applications, but it has not been fully elucidated. Long non-coding RNAs (lncRNAs) have been shown to play a key role in the self-renewal and pluripotency maintenance of hESCs. We previously reported that the lncRNA ESRG, which is highly expressed in undifferentiated hESCs, can maintain the self-renewal and pluripotency of hPSCs. RNA pull-down mass spectrometry showed that ESRG could bind to other proteins, among which heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) attracted our attention...

Pathogenic germline CDH1 mutation confers high risk for developing diffuse gastric and lobular breast cancers in asymptomatic carriers. In these individuals, the estimated gastric cancer risk at 80 years of age is up to 70% for males and 56% for females. Due to this high-risk predisposition, prophylactic total gastrectomy is considered a unique life-saving approach in germline CDH1 carriers, as endoscopy often fails to detect early stage diffuse gastric carcinoma. However, surgical indication is controversial in some clinical contexts, with possible contraindications...