Gastric Intraepithelial Neoplasia Research Articles

VENet: Variational energy network for gland segmentation of pathological images and early gastric cancer diagnosis of whole slide images

Background and objective: Gland segmentation of pathological images is an essential but challenging step for adenocarcinoma diagnosis. Although deep learning methods have recently made tremendous progress in gland segmentation, they have not given satisfactory boundary and region segmentation results of adjacent glands. These glands usually have a large difference in glandular appearance, and the statistical distribution between the training and test sets in deep learning is inconsistent. These problems make networks not generalize well in the test dataset, bringing difficulties to gland segmentation and early cancer diagnosis.Methods: To address these problems, we propose a Variational Energy Network named VENet with a traditional variational energy Lv loss for gland segmentation of pathological images and early gastric cancer detection in whole slide images (WSIs). It effectively integrates the variational mathematical model and the data-adaptability of deep learning methods to balance boundary and region segmentation. Furthermore, it can effectively segment and classify glands in large-size WSIs with reliable nucleus width and nucleus-to-cytoplasm ratio features.Results: The VENet was evaluated on the 2015 MICCAI Gland Segmentation challenge (GlaS) dataset, the Colorectal Adenocarcinoma Glands (CRAG) dataset, and the self-collected Nanfang Hospital dataset. Compared with state-of-the-art methods, our method achieved excellent performance for GlaS Test A (object dice 0.9562, object F1 0.9271, object Hausdorff distance 73.13), GlaS Test B (object dice 94.95, object F1 95.60, object Hausdorff distance 59.63), and CRAG (object dice 95.08, object F1 92.94, object Hausdorff distance 28.01). For the Nanfang Hospital dataset, our method achieved a kappa of 0.78, an accuracy of 0.9, a sensitivity of 0.98, and a specificity of 0.80 on the classification task of test 69 WSIs.Conclusions: The experimental results show that the proposed model accurately predicts boundaries and outperforms state-of-the-art methods. It can be applied to the early diagnosis of gastric cancer by detecting regions of high-grade gastric intraepithelial neoplasia in WSI, which can assist pathologists in analyzing large WSI and making accurate diagnostic decisions.

Establishment and Evaluation of a Risk Prediction Model for Pathological Escalation of Gastric Low-Grade Intraepithelial Neoplasia.

The study aims to explore the risk factors for pathological escalation after endoscopic surgery for gastric low-grade intraepithelial neoplasia (LGIN) and to establish and evaluate a risk prediction model for LGIN. A total of 120 patients diagnosed with gastric LGIN by biopsy and endoscopic submucosal dissection (ESD) between November 2020 and June 2022 were retrospectively analyzed. Gender, age, Helicobacter pylori (HP) infection, lesion size, lesion location, morphology, gastric mucosal congestion, nodules status, surface ulceration and erosion, and ME-observation of all patients were collected and divided into upgraded and non-upgraded groups according to the biopsy and ESD postoperative pathological diagnosis results. Independent risk factors for pathological escalation after ESD surgical treatment were screened by logistic regression analysis, and a risk prediction model was established. Among the 120 patients with gastric LGIN, 49 patients developed postoperative pathological upgrading; the rate of pathological upgrading was 40.83%. Among them, 42 patients were upgraded to high-grade intraepithelial neoplasia (HGIN), 1 case was upgraded to advanced gastric cancer, and 6 cases were upgraded to early gastric carcinoma (EGC). Univariate analysis showed that age, lesion size, gastric mucosal congestion, surface ulcers, and erosion were significantly different between the groups (p < 0.05). Multivariate Logistic regression analysis revealed that age ≥60 years, focal length ≥2 cm, gastric mucosal congestion, and surface ulceration and erosion were independent risk factors for postoperative pathological escalation in patients with gastric LGIN. Final joint probability forecasting model for P = 1/[1 + e(26.515-0.161 x β1-0.357 x β2+0.039 x β3-0.269 x β4)]. Age, lesion size ≥2 cm, gastric mucosal congestion, and lesion surface ulceration and erosion are risk factors for postoperative pathological upgrading in patients with gastric LGIN. The risk prediction model established in this study based on risk factors has predictive value and can provide a scientific reference for the clinical treatment of patients with gastric LGIN.

Data-independent acquisition (DIA) mass spectrometry reveals related proteins involved in the occurrence of early intestinal-type gastric cancer.

Identifying proteins associated with the onset of early intestinal-type gastric cancer (EIGC) can yield valuable insights into the pathogenesis of this specific subtype of gastric cancer. Data-independent acquisition mass spectroscopy (DIA-MS) was utilized to identify the differential protein between 10 cases of EIGC and atrophic gastritis with intestinal metaplasia (NGC). The expressions of IPO4, TBL1XR1, p62/SQSTM1, PKP3, and CRTAP were verified by immunohistochemistry (IHC) in 20 EIGC samples, 17 gastric low-grade intraepithelial neoplasia (LGIN) samples, and 21 healthy controls. The prognostic values of the five genes were validated in the transcriptome data by survival analysis. A total of 4,028 proteins were identified using DIA-MS and a total of 177 differential proteins were screened with log2(fold change) > 1.5. Among them, 113 proteins were significantly up-regulated, and 64 proteins were significantly down-regulated in EIGC tissues. IHC results showed that proteins IPO4, TBL1XR1, p62/SQSTM1, PKP3, and CRTAP were highly expressed in the cytoplasm of EIGC and LGIN, which was consistent with the results of DIA-MS. Among them, p62/SQSTM1 may undergo nuclear-cytoplasmic transfer. The five protein-coding genes were associated with intestinal-type gastric cancer survival and exhibited differential expression across various disease stages. The study successfully identified differentially expressed proteins between EIGC and NGC, providing potential biomarkers and valuable insights into the mechanism underlying intestinal-type gastric cancer.

Characteristics of multiple early gastric cancer and gastric high-grade intraepithelial neoplasia.

This study evaluated the clinical characteristics of multiple early gastric cancer (MEGC) and high-grade intraepithelial neoplasia (HGIN) treated by endoscopic submucosal dissection. The clinical profiles of 23 patients with MEGC treated by endoscopic submucosal dissection from January 2008 to June 2019 at the Fujian Provincial Hospital or Fujian Provincial Hospital South Branch were analyzed. The following information was extracted from clinical records: general data, preoperative conditions, and pathological data of each lesion after surgery. In total, 23 patients with MEGC or HGIN were evaluated (average age 64 ± 6 years, 17 (73.9%) males). MEGC and HGIN accounted for 4.9 percent of all cases, in which 19 (4.1%) were synchronous multiple cancers and 4 (0.8%) cases were metachronous multiple cancers. Lesions of synchronous and metachronous MEGC groups did not differ in age, sex, smoking history, alcohol consumption, family history of tumors, Helicobacter pylori infection, mucosal background atrophy, or intestinal metaplasia (P > .05). The vertical locations of primary and secondary lesions of MEGC were correlated (R = 0.395, P = .034). The primary and secondary lesions of MEGC shared the same macroscopic subtype (R = 0.590, P = .015), infiltration depth (R = 0.455, P = .014), and pathological subtype (R = 0.736, P < .001). MEGC and HGIN were located in close proximity. Pathologic types tended to be low-grade malignancies. The macroscopic type, histology type, and infiltration depth of the 2 lesions were significantly correlated. When detecting early gastric cancer, we should inspect the stomach and carefully consider the pathological characteristics, to improve the diagnosis of MEGC.

SERPINB5 is a novel serum diagnostic biomarker for gastric high-grade intraepithelial neoplasia and plays a role in regulation of macrophage phenotypes

BackgroundGastric cancer (GC) develops from gastric precancerous lesions (GPL), and early diagnosis and treatment at the premalignant stage may achieve a higher benefit‒cost ratio with a reduced necessity for surgery. However, reliable noninvasive screening biomarkers of GPL are currently lacking. MethodsThe marker genes of GPL encoding extracellular proteins were identified by bioinformatics analysis and further verified by immunofluorescence and immunohistochemistry assays. Serum samples were collected to measure the levels of SERPINB5, the diagnostic efficacy of which was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). Finally, the effect of SERPINB5 on the phenotypic conversion of macrophages was verified by public data and in vitro experiments. ResultsSERPINB5 was identified as an extracellular biomarker of GPL that had good diagnostic efficacy. High expression of SERPINB5 was observed in the epithelial cells and adjacent extracellular matrix on sections of gastric high-grade intraepithelial neoplasia (HGIN). Importantly, SERPINB5 determined in serum was significantly increased in the HGIN group, and the AUC for discriminating between HGIN and chronic gastritis or low-grade intraepithelial neoplasia was 0.9936 and 0.9750, respectively. Moreover, SERPINB5 expression was positively correlated with macrophage infiltration, and M1 marker NOS2 expression, but negatively correlated with M2 marker CSF1R expression. In THP-1-derived macrophages, SERPINB5 upregulated expression of M1-related cytokines TNF-α and IL-12, and M1 marker CD86, but suppressed production of M2-related cytokines TGF-β and IL-10. ConclusionsOur study provides evidence that SERPINB5 may serve as a promising noninvasive serum biomarker for gastric HGIN screening and regulate macrophage phenotype conversion.

Application of serum gastric function markers and digestive tumor indices to the diagnosis of early gastric cancer and precancerous lesions.

To study the levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 199, CA724, CA242, pepsinogen (PG) I, PGII, gastrin-17 (G-17), the PGI/PGII ratio (PGR), as well as the expression of p27 and Ki67, in patients suffering from early gastric cancer and intraepithelial neoplasia and to provide new markers for the diagnosis of early gastric cancer and precancerous lesions. A retrospective study where the blood serum concentration of CEA, CA199, CA724, CA242, PGI, PGII, G-17 and PGR were tested and also the protein expression of p27 and Ki67 was detected in patients tissues by immunohistochemistry in the Gastrointestinal Endoscopy Center of the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China, from March 2018 to March 2021. Carbohydrate antigen 242 and CA199 levels in tumor tissue significantly differed among the groups. Pepsinogen I levels decreased with increasing disease severity, G-17 levels increased with the aggravation of severity, and p27 expression decreased with the severity. The combination of serum gastric function markers (PGI and G-17) and p27 digestive tumor indices can serve as markers for the diagnosis of early gastric cancer and intraepithelial neoplasia.

Quantitative Analysis on Molecular Characteristics Evolution of Gastric Cancer Progression and Prognosis.

The dynamic changes of key biological characteristics from gastric low-grade intraepithelial neoplasia (LGIN) to high-grade intraepithelial neoplasia (HGIN) to early gastric cancer (EGC) are still unclear, which greatly affect the accurate diagnosis and treatment of EGC and prognosis evaluation of gastric cancer (GC). In this study, bioinformatics methods/tools are applied to quantitatively analyze molecular characteristics evolution of GC progression, and a prognosis model is constructed. This study finds that some dysregulated differentially expressed mRNAs (DEmRNAs) in the LGIN stage may continue to promote the occurrence and development of EGC. Among the LGIN, HGIN, and EGC stages, there are differences and relevance in the transcription expression patterns of DEmRNAs, and the activation related to immune cells is very different. The biological functions continuously changed during the progression from LGIN to HGIN to EGC. The COX model constructed based on the three EGC-related DEmRNAs has GC prognostic risk prediction ability. The evolution of biological characteristics during the development of EGC mined by the authors provides new insight into understanding the molecular mechanism of EGC occurrence and development. The three-gene prognostic risk model provides a new method for assisting GC clinical treatment decisions.

Clinical value of serum Mg7-Ag detection combined with magnifying endoscopy with narrow-band imaging in diagnosis of high-risk gastric low-grade intraepithelial neoplasia

Clinical value of serum Mg7-Ag detection combined with magnifying endoscopy with narrow-band imaging in diagnosis of high-risk gastric low-grade intraepithelial neoplasia

Determination of an Appropriate Endoscopic Monitoring Interval for Patients with Gastric Precancerous Conditions in China.

Gastric precancerous conditions such as atrophic gastritis (AG) and intestinal metaplasia (IM) are considered independent risk factors for gastric cancer (GC). The suitable endoscopic monitoring interval is unclear when we attempt to prevent GC development. This study investigated the appropriate monitoring interval for AG/IM patients. Totally, 957 AG/IM patients who satisfied the criteria for evaluation between 2010 and 2020 were included in the study. Univariate and multivariate analyses were used to determine the risk factors for progression to high-grade intraepithelial neoplasia (HGIN)/GC in AG/IM patients, and to determine an appropriate endoscopic monitoring scheme. During follow-up, 28 AG/IM patients developed gastric neoplasia lesions including gastric low-grade intraepithelial neoplasia (LGIN) (0.7%), HGIN (0.9%), and GC (1.3%). Multivariate analysis identified H. pylori infection (P=0.022) and extensive AG/IM lesions (P=0.002) as risk factors for HGIN/GC progression (P=0.025). In our study, HGIN/GC was present in 2.2% of AG/IM patients. In AG/IM patients with extensive lesions, a 1-2-year surveillance interval is recommended for early detection of HIGN/GC in AG/IM patients with extensive lesions.

Evaluation of the detection rate of high‑grade gastric intraepithelial neoplasia using linked color imaging and white light imaging.

As an endoscopic technology for the enhancement of images, linked color imaging (LCI) performs well when used for the early detection and diagnosis of gastrointestinal cancer. However, literature data are lacking for LCI in the detection of high-grade gastric intraepithelial neoplasia. Therefore, the aim of the present study was to investigate the efficacy of LCI compared with traditional white light imaging (WLI) in the detection of high-grade gastric intraepithelial neoplasia via the comparison of detection rates between senior and junior endoscopists using both techniques. Overall, 84 lesions from 81 patients with high-grade gastric intraepithelial neoplasia diagnosed between January 2017 and December 2017 were considered. Following the exclusion of three patients with two lesions, 78 patients who had only one lesion were enrolled. The two types of endoscopy, WLI and LCI, were performed in the same patients under the same conditions. Four senior and four junior endoscopists retrospectively compared the images. The detection rate of high-grade gastric intraepithelial neoplasia was significantly higher with LCI than with WLI when performed by senior and junior endoscopists. With WLI, the detection rate obtained by senior endoscopists was significantly higher than that obtained by junior endoscopists. However, for LCI, the detection rates for junior and senior endoscopists were comparable. Interobserver agreement was good to satisfactory. These findings indicate that LCI is superior to WLI in the detection and identification of gastric cancer and provides highly accurate diagnostic results from endoscopic examinations, regardless of the experience of the endoscopist. LCI may be used to narrow the gap in the detection rate of high-grade gastric intraepithelial neoplasia between junior and senior endoscopists.

Diagnosis and segmentation effect of the ME-NBI-based deep learning model on gastric neoplasms in patients with suspected superficial lesions - a multicenter study.

Endoscopically visible gastric neoplastic lesions (GNLs), including early gastric cancer and intraepithelial neoplasia, should be accurately diagnosed and promptly treated. However, a high rate of missed diagnosis of GNLs contributes to the potential risk of the progression of gastric cancer. The aim of this study was to develop a deep learning-based computer-aided diagnosis (CAD) system for the diagnosis and segmentation of GNLs under magnifying endoscopy with narrow-band imaging (ME-NBI) in patients with suspected superficial lesions. ME-NBI images of patients with GNLs in two centers were retrospectively analysed. Two convolutional neural network (CNN) modules were developed and trained on these images. CNN1 was trained to diagnose GNLs, and CNN2 was trained for segmentation. An additional internal test set and an external test set from another center were used to evaluate the diagnosis and segmentation performance. CNN1 showed a diagnostic performance with an accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 90.8%, 92.5%, 89.0%, 89.4% and 92.2%, respectively, and an area under the curve (AUC) of 0.928 in the internal test set. With CNN1 assistance, all endoscopists had a higher accuracy than for an independent diagnosis. The average intersection over union (IOU) between CNN2 and the ground truth was 0.5837, with a precision, recall and the Dice coefficient of 0.776, 0.983 and 0.867, respectively. This CAD system can be used as an auxiliary tool to diagnose and segment GNLs, assisting endoscopists in more accurately diagnosing GNLs and delineating their extent to improve the positive rate of lesion biopsy and ensure the integrity of endoscopic resection.

Mitochondrial Function in Health and Disease: Responses to Helicobacter pylori Metabolism and Impact in Gastric Cancer Development.

Mitochondria are major cellular organelles that play an essential role in metabolism, stress response, immunity, and cell fate. Mitochondria are organized in a network with other cellular compartments, functioning as a signaling hub to maintain cells' health. Mitochondrial dysfunctions and genome alterations are associated with diseases including cancer. Mitochondria are a preferential target for pathogens, which have developed various mechanisms to hijack cellular functions for their benefit. Helicobacter pylori is recognized as the major risk factor for gastric cancer development. H. pylori induces oxidative stress and chronic gastric inflammation associated with mitochondrial dysfunction. Its pro-apoptotic cytotoxin VacA interacts with the mitochondrial inner membrane, leading to increased permeability and decreased ATP production. Furthermore, H. pylori induces mitochondrial DNA damage and mutation, concomitant with the development of gastric intraepithelial neoplasia as observed in infected mice. In this chapter, we present diverse aspects of the role of mitochondria as energy supplier and signaling hubs and their adaptation to stress conditions. The metabolic activity of mitochondria is directly linked to biosynthetic pathways. While H. pylori virulence factors and derived metabolites are essential for gastric colonization and niche adaptation, they may also impact mitochondrial function and metabolism, and may have consequences in gastric pathogenesis. Importantly, during its long way to reach the gastric epithelium, H. pylori faces various cellular types along the gastric mucosa. We discuss how the mitochondrial response of these different cells is affected by H. pylori and impacts the colonization and bacterium niche adaptation and point to areas that remain to be investigated.

Correlation analysis of gastric mucosal lesions with Helicobacter pylori infection and its virulence genotype in Guiyang, Guizhou province, China.

Helicobacter Pylori (H. pylori) infection is the most important factor affecting clinical outcome in patients with gastric mucosal lesions. This study aimed to investigate H. pylori infection in patients with gastric mucosal lesions and their virulence genotype in Guiyang, China. Pathological examinations of 1,364 biopsies from patients with upper gastrointestinal symptoms and H. pylori infection were analyzed according to different pathological types. The bacterial genome DNA was extracted from H. pylori strains isolated from gastric biopsies, and the cagA, vacA, and iceA virulence genes were detected and typed to analyze the correlation of their genotypes between different pathological lesions. The positive rate of H. pylori infection was approximately 19.9% (272/1,364), as determined by histopathological examination (HPE). It was more frequently detected in men than in women. A total of 85 H. pylori isolates were obtained from 280 clinical samples (positive rate 30.4%, 85/280). Of these 85 strains, cagA, vacA, and iceA genes were identified in 85.9%, 100%, and 83.5% of samples, respectively. Approximately 74.1% of strains were cagA East Asian type (cagA-ABD), and 11.8% of were cagA Western strains (cagA-AB, cagA-ABC), only present in patients with chronic non-atrophic gastritis. Gastric intraepithelial neoplasia and gastric cancer harbored both Asian strains. A total of 7 combinations of vacA genotypes were noted, among which s1c/m1b (30.6%) and s1c/m2 (41.2%) were the dominant genotypes. The predominant iceA genotype was iceA1 (64.7%). We observed that the positive rate of H. pylori infection was related to the pathological type of patients' gastric mucosal lesions. Isolated H. pylori strains showed a unique genotype, mainly East Asian type cagA (ABD), vacA s1c/m2 genotype, and iceA1. These results provide an important reference for further studies of H. pylori in Guizhou province, China.

Multiplexed immunofluorescence analysis of CAF-markers, EZH2 and FOXM1 in gastric tissue: associations with clinicopathological parameters and clinical outcomes

BackgroundThe aim of this study is to explore the expression and clinical relevance of CAF-associated markers, EZH2 and FOXM1 in gastric samples.MethodsProtein expression were detected and evaluated by multi-plex immunofluorescence (mIF) in 93 cases of gastric cancer (GC) and 31 cases of gastric intraepithelial neoplasia (GIN). The correlation among their expression, and the relationship of them with clinicopathological parameters and prognosis in GC were then analyzed.ResultsFAP was specific expressed in the CAFs of GC samples, and thus be utilized as a CAF-associated marker in our subsequently analysis. The immunostaining of EZH2, FOXM1 and FAP were significantly upregulated in patients with GC tissues than in those normal gastric mucosa or GIN tissues. The average fluorescence intensity of FAP was slightly positively correlated with EZH2 in GC, GIN and normal samples, whereas the percentage of FAP positive cells has no correlation with that of EZH2. Both the percentage of positive cells and the average fluorescence intensity of FOXM1 were positively correlated with that of FAP and EZH2 in GC, GIN and normal samples, except for FOXM1 and EZH2 expression in normal tissue samples. No significant association was observed between FAP expression and any clinicopathological parameters, whereas the positive frequency of EZH2 and FOXM1 were correlated with tumor location significantly and tumor invasion depth, respectively. In addition, there was strong positive correlations between FAP protein expression and overall survival (OS) and disease-free survival (DFS), and EZH2 expression was positively associated with OS in patients with GC. Furthermore, EZH2 and FAP protein expression was an independent prognostic factor for OS and DFS, respectively.ConclusionsThese results suggest that both EZH2 and FOXM1 expression was positively associated with CAFs abundance in GC. They may be potential cellular target for therapeutic intervention, especially in patients with a large number of CAFs.

Prognostic factors in the treatment of gastric mucosal atypical hyperplasia by endoscopic submucosal dissection

BackgroundEndoscopic submucosal dissection (ESD) is becoming increasingly popular as a treatment for precancerous lesions and early cancers of the stomach. However, there have been few studies on the factors associated with the recurrence of precancerous lesions after ESD.MethodsTo investigate the prognostic factors of gastric intraepithelial neoplasia, we retrospectively analyzed 115 patients who were treated with ESD between February 2018 and January 2020. Chi-square test and Fisher’s extract test were used to select factors for further investigation, and prognostic analysis was carried out with the Kaplan–Meier method and a Cox regression model.ResultsPlatelet counts (P = 0.027) and albumin levels (P = 0.011) were both lower in patients with recurrence than in patients without recurrence of gastric mucosal atypical hyperplasia after ESD.ConclusionsThis study reveals that low platelet counts and albumin levels were probably unfavorable prognostic factors in mucosal atypical hyperplasia of the stomach.

A deep learning and natural language processing-based system for automatic identification and surveillance of high-risk patients undergoing upper endoscopy: A multicenter study.

Timely identification and regular surveillance of patients at high risk are crucial for early diagnosis of upper gastrointestinal cancer. However, traditional manual surveillance method is time-consuming, and current surveillance rate is below 50%. Here, we aimed to develop a surveillance system named ENDOANGEL-AS (automatic surveillance) for automatic identification and surveillance of high-risk patients. 7874 patients from Renmin Hospital of Wuhan University between May 1 and July 31, 2021 were used as the training set, 6762 patients between August 1 and October 31, 2021 as the internal test set, and 7570 patients from two other hospitals between August 1 and October 31, 2021 as the external test sets. We first extracted descriptions of abnormalities from endoscopic and pathological reports based on natural language processing techniques to identify individuals. Then patients were classified at nine risk levels according to endoscopic and pathological findings, and a deep learning model was trained to identify demarcation line (DL) in gastric low-grade intraepithelial neoplasia (LGIN) using 1561 white-light still images for risk stratification of gastric LGIN. Finally, patients undergoing upper endoscopy were classified and assigned one of ten surveillance intervals according to guidelines. The performance of ENDOANGEL-AS was evaluated and compared with physicians. Patient identification module achieved an accuracy of 100% and 99.91% in internal and external test sets, respectively. Risk level classification module achieved an accuracy of 100% and 99.85% in the internal and external test sets, respectively. DL identification module achieved an accuracy of 87.88%. ENDOANGEL-AS on surveillance interval assignment achieved an accuracy of 99.23% and 99.67% in internal and external test sets, respectively. ENDOANGEL-AS had significantly higher accuracy compared with physicians (99.00% vs 38.87%, p<0.001). The accuracy (63.67%, p<0.001) of endoscopists with the assistance of ENDOANGEL-AS was significantly improved. We established a surveillance system that can automatically identify patients and assign surveillance intervals with high accuracy and good transferability. This work was partly supported by a grant from the Hubei Province Major Science and Technology Innovation Project (2018-916-000-008) and the Fundamental Research Funds for the Central Universities (2042021kf0084).

Study on molecular biological mechanism of Chinese herbal medicines for the treatment of gastric precancerous lesions based on data mining and network pharmacology.

To explore the molecular biological mechanisms of Chinese herbal medicines for the treatment of gastric precancerous lesions by data mining and network pharmacology. The keywords "gastric precancerous lesions""gastric precancerous disease""gastric mucosal intraepithelial neoplasia""gastric mucosal heterogeneous hyperplasia""gastric precancerous state""chronic gastritis, atrophic""combined Chinese and Western medicine""Chinese medicine therapy""efficacy evaluation" "randomized controlled trial"were searched in China Journal Full-text Database, Wanfang Data, VIP database, PubMed and Embase from 2001 to 2021. The information was extracted from the literature which met the inclusion and exclusion criteria, and the database was constructed to identify the high-frequency herbal medicines. The top six Chinese herbal medicines were analyzed by the network pharmacology methods, including the acquisition of herbs compounds and gastric precancerous lesions targets using Pharmacology Database and Analysis Platform and GeneCards databases, construction of protein-protein interaction network, and screening of core targets, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of core targets through Metascape platform, etc., to elucidate their active components, targets and pathways. A total of 482 compound prescriptions with 603 herbal medicines were included, and the top 6 herbal medicines with higher application frequency were Ume plum (63.35%), Curcuma longa (58.54%), Paeonia lactiflora (54.06%), Salvia miltiorrhiza (49.92%), Rhizoma alba (46.43%), and Astragalus membranaceus (45.44%). The results of the network pharmacological analysis showed that the active ingredients were 4 types from Ume plum, 3 from Curcuma longa, 9 from Paeonia lactiflora, 13 from Salvia miltiorrhiza, 7 from Astragalus alba, and 9 from Astragalus; 77 predicted targets were in Ume plum, 11 in Curcuma longa, 33 in Paeonia lactiflora, 58 in Salvia miltiorrhiza, 65 in Astragalus alba and 89 in Astragalus; and 98 crossover genes were obtained after these targets were compared with the disease genes, among which HSP90AA1, AKT1, TP53, STAT3, MAPK1 and TNF had higher relevance to the treatment of gastric precancerous lesions. The results of the GO enrichment analysis showed that the active ingredients of high frequency Chinese medicine mostly acted through biological processes such as response to inorganic substance, response to hormone, gland development, positive regulation of cell migration, positive regulation of cell motility, etc. The targets include cellular components such as vesicle lumen, secretory granule lumen, cytoplasmic vesicle lumen, transcription regulator complex, and with molecular functions such as kinase binding, protein kinase binding and DNA-binding transcription factor binding. The results of the KEGG pathway enrichment analysis showed that Paeonia lactiflora, Ulmus lucidus, Salvia miltiorrhiza and Astragalus mainly act through the cancer pathway and PI3K-AKT pathway; Curcuma longa and Rhizoma alba mainly act through the cancer pathway and proteoglycans in cancer, and all six herbs were involved in the cancer pathway and five herbs are involved in the PI3K-AKT pathway. In this study, we obtained the top 6 high-frequency Chinese herbal medicines in the treatment of gastric precancerous lesions by data mining method, and revealed that their mechanisms are involved in cell proliferation, differentiation, immunity, inflammation and other processes mainly through cancer pathway, PI3K-AKT signaling pathway, proteoglycans in cancer.

Proteomic Analysis Reveals Molecular Differences in the Development of Gastric Cancer.

Gastric cancer (GC) is the 3rd leading cause of death from cancer and the 5th most common cancer worldwide. The detection rate of GC among Tibetans is significantly higher than that in Han Chinese, probably due to differences in their living habits, dietary structure, and environment. Despite such a high disease burden, the epidemiology of gastric cancer has not been studied in this population. Molecular markers are required to aid the diagnosis and treatment of GC. In this study, we collected gastric tissue samples from patients in Tibet with chronic nonatrophic gastritis (CNAG) (n = 6), chronic atrophic gastritis (CAG) (n = 7), gastric intraepithelial neoplasia (GIN) (n = 4), and GC (n = 5). The proteins in each group were analyzed using coupled label-free mass spectrometry. In addition, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein interaction networks were used to analyze the differentially expressed proteins (DEPs) among groups. DEPs were quantified in comparisons of GC versus CNAG (223), GC versus GIN (100), and GIN versus CNAG (341). GO and KEGG analyses showed that the DEPs were mainly associated with immunity (GC versus CNAG) and cancer proliferation and metastasis (GC versus GIN, and GIN versus CNAG). Furthermore, the expression levels of cell proliferation and cytoskeleton-related proteins increased consistently during cancer development, such as ITGA4, DDC, and CPT1A; thus, they are potential diagnostic markers. These results obtained by proteomics analysis could improve our understanding of cancer biology in GC and provide a rich resource for data mining and discovering potential immunotherapy targets.

A Single-Center Follow-Up Study of Low-Grade Gastric Intraepithelial Neoplasia and the Screening of Key Genes of Precancerous Lesions.

ObjectiveThe study aimed to summarize the morphological characteristics of low-grade gastric intraepithelial neoplasia (LGIN) and explore its outcomes and risk factors. Additionally, it aimed to screen the core different expression genes (DEGs) of high-grade gastric intraepithelial neoplasia (HGIN) using bioinformatics methods to identify biomarkers for early gastric cancer outcomes.MethodsThe clinical and pathological data of 449 patients with LGIN in the endoscopy center of the Second Hospital of Hebei Medical University from June 2013 to September 2018 were collected for retrospective analysis. The GSE130823 and GSE55696 data sets were selected from the Gene Expression Omnibus database, and the GEO2R tool was used to screen DEGs in HGIN and chronic gastritis tissue types. A DEG functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery. The STRING database was utilized to create a protein–protein interaction network, and the CytoHubba plug-in was used to screen the key genes of HGIN.ResultsThe incidence of LGIN increased with age, and most of the patients were aged between 45–59 years (P = 0.048). Lesions were found mainly in the cardia, mostly in people aged 60 (P < 0.05). Progression occurred in 42 of 449 patients, with a 9.4% rate of cancer development. Foci larger than 10 mm, ulcerative lesions, and an Helicobacter pylori-positive result were factors affecting the outcome of LGIN (P < 0.05). Seven core genes of HGIN were screened, including MYC, SOX2, CDX2, TBX3, KRT7, CDKN2A, and MUC5AC.ConclusionThe patients with LGIN reflected the potential for developing cancer. A magnifying gastroscope can contribute to the detection of early gastric cancer. Additionally, the MYC, CDX2, and TBX3 genes may act as specific biomarkers of HGIN.

Comparison of Endoscopic Radiofrequency Ablation and Argon Plasma Coagulation in Patients with Gastric Low-Grade Intraepithelial Neoplasia: A Large-Scale Retrospective Study.

Background Gastric low-grade intraepithelial neoplasia (LGIN) is a precancerous lesion of gastric cancer. Endoscopic therapies represented by radiofrequency ablation (RFA) and argon plasma coagulation (APC) have been applied to treat gastric LGIN in recent years. However, no comparative study examining the effectiveness and safety profiles of RFA and APC has been reported. Methods A single-center, large-scale, retrospective study, including 73 and 50 patients treated with RFA and APC, respectively, was conducted in the First Medical Center of Chinese PLA General Hospital from October 2015 to October 2020, with a two-year follow-up. Effectiveness, complications, operative factors, and other data were assessed. Results At 2 years of follow-up, cure, relapse, recurrence, and progression rates were 90.4%, 9.6%, 9.6%, and 2.7% in the RFA group, respectively, versus 90%, 10%, 12%, and 4% in the APC group, respectively, with no statistically significant differences between the two groups (all p > 0.05). However, the mean lesion size was significantly larger in the RFA group (2.6 ± 1.0 cm) than in the APC group (1.5 ± 0.6 cm) (p < 0.001); there was also a significant difference in the composition ratio of large lesions between the two groups (p < 0.001). No serious postoperative complications showed in either group, and the abdominal pain was the most common symptom in the short term after surgery. Conclusions RFA and APC are both safe and effective destructive therapies for gastric LGIN. RFA is more suitable for flat and large lesions, while APC is more suitable for small lesions, especially those with slight local uplift or depression. An intraoperative submucosal injection is expected to be an effective method for relieving postoperative abdominal pain.