Gastric Tumors Research Articles

Helicobacter pylori promotes gastric cancer progression by activating the TGF-β/Smad2/EMT pathway through HKDC1.

Helicobacter pylori (H. pylori) infection is widely acknowledged as the primary risk factor for gastric cancer, facilitating its progression via the Correa cascade. Concurrently, Hexokinase Domain Containing 1 (HKDC1) has been implicated in the mediation of aerobic glycolysis, contributing to tumorigenesis across various cancers. However, the precise role of HKDC1 in the inflammatory transformation associated with H. pylori-induced gastric cancer remains elusive. In this study, transcriptome sequencing revealed a significant correlation between HKDC1 and H. pylori-induced gastric cancer. Subsequent validation using qRT-PCR, immunohistochemistry, and Western blot analysis confirmed elevated HKDC1 expression in both human and murine gastritis and gastric tumors. Moreover, in vitro and in vivo experiments demonstrated that H. pylori infection up-regulates TGF-β1 and p-Smad2, thereby activating the epithelial-mesenchymal transition (EMT) pathway, with HKDC1 playing a pivotal role. Suppression of HKDC1 expression or pharmacological inhibition of TGF-β1 reversed EMT activation, consequently reducing gastric cancer cell proliferation and metastasis. These results underscore HKDC1's essential contribution to H. pylori-induced gastric cancer progression via EMT activation.

The indolent behaviour of type 1 gastric neuroendocrine tumours smaller than 1 cm: a single western center experience

The indolent behaviour of type 1 gastric neuroendocrine tumours smaller than 1 cm: a single western center experience

Anatomic and Reconstructive Considerations During Gastric GIST Resection

Gastric gastrointestinal stromal tumors (GISTs) are the most common type of GISTs in the gastrointestinal tract. Gastric GISTs may present in a wide variety of sizes and locations in the stomach. The goal of the surgical and/or endoscopic treatments is a complete R0 resection with free margins, and combined methods to accomplish this resection are available. This manuscript will review the various surgical and/or endoscopic techniques available and the technical considerations for appropriate gastric GIST resections.

Selecting Targets for Molecular Imaging of Gastric Cancer: An Immunohistochemical Evaluation.

Tumor-targeted positron emission tomography (PET) and fluorescence-guided surgery (FGS) could address current challenges in pre- and intraoperative imaging of gastric cancer. Adequate selection of molecular imaging targets remains crucial for successful tumor visualization. This study evaluated the potential of integrin αvβ6, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM) and human epidermal growth factor receptor-2 (HER2) for molecular imaging of primary gastric cancer, as well as lymph node and distant metastases. Expression of αvβ6, CEACAM5, EGFR, EpCAM and HER2 was determined using immunohistochemistry in human tissue specimens of primary gastric adenocarcinoma, healthy surrounding stomach, esophageal and duodenal tissue, tumor-positive and tumor-negative lymph nodes, and distant metastases, followed by quantification using the total immunostaining score (TIS). Positive biomarker expression in primary gastric tumors was observed in 86% for αvβ6, 72% for CEACAM5, 77% for EGFR, 93% for EpCAM and 71% for HER2. Tumor expression of CEACAM5, EGFR and EpCAM was higher compared to healthy stomach tissue expression, while this was not the case for αvβ6 and HER2. Tumor-positive lymph nodes could be distinguished from tumor-negative lymph nodes, with accuracy ranging from 82 to 93% between biomarkers. CEACAM5, EGFR and EpCAM were abundantly expressed on distant metastases, with expression in 88-95% of tissue specimens. Our findings show that CEACAM5, EGFR and EpCAM are promising targets for molecular imaging of primary gastric cancer, as well as visualization of both lymph node and distant metastases. Further clinical evaluation of PET and FGS tracers targeting these antigens is warranted.

Mechanistic insights into traditional Chinese medicine for digestive tract cancers: implications for gastric, hepatic, esophageal, intestinal, and pancreatic tumors

Abstract The increasing incidence of cancer-related deaths highlights the pressing need for effective treatment modalities, particularly in the context of digestive tract cancers, such as gastric, hepatic, esophageal, intestinal, and pancreatic tumors. While conventional drug therapies play a critical role in managing these malignancies, their associated side effects often pose significant challenges to patient quality of life. Thus, there is a growing focus on traditional Chinese medicine (TCM) and its compounds, which are safe, non-toxic, and reliable. During anti-tumor therapy, TCM compounds, based on their multi-target, multi-pathway, and multi-level regulatory effects, fully mobilize multiple mechanisms of the body, presenting significant advantages in inhibiting tumor development, boosting patient welfare, and increasing their lifespan. This article reviews the mechanisms by which TCM inhibits tumor cell proliferation, promotes tumor cell death, suppresses tumor cell invasion and metastasis, regulates the tumor microenvironment, inhibits angiogenesis, and enhances anti-tumor drug resistance. This knowledge might provide a theoretical and scientific basis for preventing and treating tumors using TCM.

Neuroendocrine carcinomas of the gastrointestinal tract : Morphology, molecular pathology, cellular origin

Neuroendocrine carcinomas (NEC) are poorly differentiated neuroendocrine neoplasms that can occur ubiquitously in the mucosa-bearing organs of the gastrointestinal tract. Based on their morphology, they are classified into large cell (LCNEC) and small cell NEC (SCNEC). The most common form of mixed differentiation is the combination with an adenocarcinoma, referred to as mixed adenoneuroendocrine carcinoma (MANEC). NEC/MANEC exhibit asignificantly poorer prognosis than the adenocarcinomas of their respective primary sites, which is inextricably linked to their typical histomorphology. Adenocarcinomas with aberrant expression of neuroendocrine markers do not show aworse clinical course. Molecularly, NEC/MANEC have aprofile comparable to the adenocarcinomas of their site of origin and aprofile divergent from neuroendocrine tumors. Analyses of gastric NEC/MANEC have shown frequent MYC amplifications, which are reflected in MYC signatures in various transcriptome analyses.The cellular origin of NEC remains asubject of controversial discussion. New insights are provided by aMYC-driven, genetically modified mouse model that led to the development of large gastric tumors. These tumors were histologically identified as LCNEC and were accompanied by both neuroendocrine and non-neuroendocrine precursor lesions. Using immunofluorescence, aderivation from resident neuroendocrine cells in the gastric corpus was demonstrated, suggesting that at least aportion of LCNEC may originate directly from neuroendocrine cells.

Neuroendocrine tumors of the stomach and pancreas. Possibilities of application of radiomics. Problems and solutions.

Background. Radiomics is promising tool contributing to the diagnosis and treatment of neuroendocrine neoplasms of various localizations. This method is often used for differential diagnosis of gastrointestinal neoplasms from other neoplasms of this localization.Aim. To demonstrate difficulties in imaging of gastrointestinal neuroendocrine tumors, as well as possibilities of radiomics in differential diagnosis.Materials and methods. Data of 12 patients with morphologically confirmed gastric neoplasms (6 - with neuroendocrine tumor, 6 - with adenocarcinoma) and data of 22 patients with morphologically confirmed pancreatic neoplasms (11 - with neuroendocrine tumor, 11 - with adenocarcinoma) who underwent CT examination of abdominal cavity organs with intravenous contrast before treatment at the Russian Scientific Center of Roentgenoradiology were used in this study. Radiomic features were extracted from the area of manually segmented gastric and pancreatic tumors in the native phase of the CT scans. Processing of the features and statistical analysis were performed using Microsoft Office Excel and free open-source software development environment for the R programming language - R-Studio.Results. Typical and atypical imaging features of gastric and pancreatic neuroendocrine tumors, peculiarities of contrast, localization and structure of neoplasms were demonstrated on the examples of CT scans. There were 15 radiomic features that were statistically significantly different in patients with neuroendocrine tumors and gastric adenocarcinomas. In the group of patients with neuroendocrine tumors and pancreatic adenocarcinomas, statistically significant differences were observed in 14 radiomic features.Conclusion. Neuroendocrine tumors of the stomach and pancreas are rare neoplasms that are not only clinically silent in most cases, but also difficult to visualize due to their small size and poor contrast characteristics. Texture analysis is a promising tool for the differential diagnosis of gastrointestinal neoplasms from other neoplasms of this localization, especially considering the difficulties of biopsy.

Correlation of preoperative CT features with intra- and postoperative parameters of endoscopic resection in patients with gastric submucosal tumor (1~3cm).

Endoscopic resection of gastric submucosal tumors (SMTs) possesses minimal trauma, expedited recovery, and reduced costs. Nonetheless, intraoperative challenges, including imprecise surgical risk assessment, prevail. Hence, we investigated the correlation between preoperative CT observation features and perioperative parameters for predicting outcomes in SMT patients. Subjects diagnosed with SMT and undergoing endoscopic surgery conducted at West China Hospital's Endoscopy Center from September 2019 to October 2023 were retrospectively selected. Endoscopic ultrasonography (EUS) and computer tomography (CT) were utilized for evaluating SMT. The study assessed the correlation between preoperative CT findings and perioperative parameters. Increased lesion size on contrast-enhanced CT correlates with increased operative duration, hospital stay, postoperative antibiotic use. Of utmost significance, we observed a significantly higher intraoperative perforation rate for patients with tumor outgrowth compared to those with lesion involvement of the lumen (96.88% vs 29.11%, P < 0.001). These patients also demonstrated an increased risk of postoperative blood stream infections (P = 0.012), necessitating higher antibiotic grade (P = 0.048), along with prolonged gastrostomy tube retention (P = 0.001) and hospitalization (P = 0.018). In addition, CT provides a more accurate and comprehensive assessment of tumor size (P = 0.037) and growth pattern (P = 0.026) than EUS. CT assessment of tumor size closer to reality than EUS. Importantly, these features can assist in pinpointing lesions with elevated surgical complexity and high risk of complications, leading to improved preoperative preparation, thereby increasing anticipation of surgical risks and reducing incidence of complications.

Mesocolic schwannoma mimicking gastrointestinal stromal tumor: A case report and review of literature.

Schwannomas are common peripheral nerve tumors originating from Schwann cells, primarily occurring in the head and neck, limbs, and trunk. Schwannomas occurring in the mesocolon are rare and often have no specific manifestations. Abdominal schwannomas need to be differentiated from common abdominal tumors such as gastrointestinal stromal tumors. We report a case of a mesocolic schwannoma in a 59-year-old female presenting with gastrointestinal symptoms of acid reflux. At an outside hospital, gastroscopy, colonoscopy, and abdominal computed tomography scans revealed a soft tissue mass adjacent to the greater curvature of the stomach, leading to a suspicion of a gastric mesenchymal tumor. Mesocolic schwannoma. Laparoscopy was performed at our hospital. Intraoperatively, the tumor was found to be closely related to the transverse colon and was initially diagnosed as a mass originating from the transverse colon. Consequently, a resection of the mass along with the adherent portion of the transverse colon was performed. Postoperative pathology and immunohistochemistry confirmed that the tumor was a schwannoma of the mesentery and did not originate from the transverse colon. Schwannomas can be distinguished from gastrointestinal stromal tumors by immunohistochemical staining, and surgical treatment is effective for benign schwannomas.

Autoimmune Gastritis in Korean Patients with Gastric Tumors: Clinicopathologic Correlations and Diagnostic Histological Features.

Autoimmune gastritis (AIG) is a corpus-dominant atrophic gastritis in which patients are positive for antiparietal cell antibody (APCA) and/or anti-intrinsic factor antibody. The risk of developing gastric cancer in patients with AIG remains unclear, and reliable frequency data of AIG in patients with gastric cancer are lacking. We included 624 Korean patients with gastric tumors (612 gastric cancers and 12 neuroendocrine tumors) who had APCA results and were available for AIG evaluation. In patients with positive APCA results, endoscopy and histology findings were reviewed to diagnose AIG. Of the 624 patients, 37 (5.9%) tested positive for APCA, and ultimately, 11 (1.8%) met the diagnostic criteria for AIG (5 both endoscopy and histology findings, 4 endoscopy-only findings, 2 histology-only findings). The frequency of AIG in patients with gastric cancer was 1.3% (8/612), and that in patients with neuroendocrine tumors was 25.0% (3/12). Of the 11 patients with AIG, serum Helicobacter pylori antibody was positive in six patients (54.5%), all of whom had gastric cancer. Histologically, three patients showed pure AIG, four patients exhibited concurrent AIG and H. pylori gastritis, and the findings for four were indefinite for AIG. The pepsinogen (PG) I levels and PG I/II ratio were significantly lower in patients with gastric cancer with AIG than in patients with gastric cancer without AIG (p=0.042 and p=0.016, respectively). The frequency of AIG in gastric cancer patients was very low compared to that in patients with neuroendocrine tumors. Rather, concurrent AIG and H. pylori gastritis was common in patients with AIG with gastric cancer.

Is Endoscopic Resection Essential for Patients with Type 1 Gastric Neuroendocrine Tumor?

Background: The gastric neuroendocrine tumor (g-NET) is now more frequently diagnosed due to the widespread use and advancement of endoscopy. In our study, we aimed to discuss the superiority, if any, between the watch-and-wait approach and endoscopic treatment methods for the controversial management of type 1 g-NETs, as well as to evaluate their long-term outcomes. Materials and Methods: The data of 81 patients who underwent gastroscopy due to complaints related to the upper gastrointestinal system and were diagnosed with type 1 g-NET as a result of biopsy taken from suspicious stomach lesions were examined. After exclusion criteria, 48 patients were included in the study. Patients were categorized into two groups: the watch-and-wait group, where no invasive procedure was performed, and the group that underwent any form of endoscopic resection. Results: Thirty-seven patients were followed up regularly without any treatment. Eleven patients were followed up after endoscopic resection (endoscopic submucosal dissection-endoscopic mucosal resection). Endoscopic resection was performed in 5 of 37 patients with tumor size <10 mm and in 6 of 11 patients with tumor size between 10 and 20 mm. The median follow-up duration for all patients was 5 years, during which no instances of metastasis, tumor progression, or mortality were observed in any patient, regardless of whether they underwent endoscopic resection or not. Conclusion: This outcome prompts a questioning of the necessity for invasive treatment methods such as endoscopic resection, which comes with a relatively high cost and the potential for complications, in this particular patient group.

Update on diagnosis and treatment in autoimmune gastritis

Autoimmune gastritis (AIG) is a special type of atrophic gastritis caused by autoimmune abnormalities. Diagnosis of AIG is often delayed because of the absence of typical symptoms in the early stage, which results in inadequate treatment and poor cancer screening. It is crucial to improve the awareness of this disease. This article summarizes the clinical manifestations, endoscopic features, and treatments of autoimmune gastritis. Conventional therapy consists of adequate iron and vitamin B12 supplementation as well as symptomatic approaches. The associated risk for gastric adenocarcinoma and gastric neuroendocrine tumors requires regular endoscopic follow up. This article is helpful in prevention and treatment of AIG.

Impact of Size on Endoluminal Approaches to Submucosal Tumors of the Stomach

Gastric subepithelial lesions (SELs) represent a heterogenous group of mass lesions that arise from the gastric mucosa. Several endoscopic techniques can be used to manage gastric SELs once the decision is made to pursue resection, including endoscopic submucosal resection, endoscopic submucosal dissection, submucosal tunnel endoscopic resection, and endoscopic full-thickness resection. In addition to other clinical and anatomic factors, lesion size has important implications on the ability to obtain a complete resection while minimizing risk of adverse events. This article reviews technical considerations and available data regarding how size may impact the endoscopic approach to gastric SEL resection.

CT feature of irregular extensive ulceration as a predictor of liver metastasis in gastric gastrointestinal stromal tumours.

This study aimed to investigate whether the computed tomography (CT) finding of irregular extensive ulceration (IEU) can serve as a predictor of liver metastasis (LIM) in patients with gastric gastrointestinal stromal tumours (GISTs). This study retrospectively collected clinical and imaging data from 286 patients diagnosed with low-, intermediate-, or high-risk gastric GISTs, or primary lesions with LIM from three medical institutions. The patients were categorised into non-LIM and LIM groups according to whether they had synchronous or metachronous LIM. Multivariate logistic regression analyses were performed to identify significant predictors of LIM. Additionally, receiver operating characteristic (ROC) curve, subgroup, and pathologic-radiologic correlation analyses were conducted. A total of 124 patients were ultimately enroled. There were significant differences in sex, site, growth pattern, size, shape, ulceration and Ki-67 expression between LIM and non-LIM groups. ROC curve analysis demonstrated that IEU had the highest area under the curve for predicting LIM (AUC = 0.842; 95% CI: 0.760-0.924; p < 0.001). Multivariate analysis indicated that IEU was the most significant independent predictor of high LIM risk (OR = 88.62; 95% CI: 2.80-2803.54; p = 0.011). Subgroup analysis showed that IEU was more frequently associated with male sex, age ≤ 55 years, proximal sites, irregular shapes, mixed growth patterns, and a high Ki-67 expression. The CT feature of IEU serves as an independent predictor of LIM in gastric GISTs and is strongly associated with high Ki-67 expression. Question Accurate assessment of LIM risk in patients with gastric GISTs is crucial, yet current non-invasive predictors remain inadequate. Findings IEU on CT is an independent predictor of LIM, with high diagnostic accuracy and a significant association with elevated Ki-67 expression. Clinical relevance IEU on CT scans enables non-invasive risk stratification for LIM in gastric GISTs. Our study refined the assessment of ulceration types, highlighting significant heterogeneity, which may guide personalised treatment strategies.

Gastric Glomus Tumor Resected by Submucosal Tunneling Endoscopic Resection

ABSTRACT Gastric glomus tumor (GGT) is a rare mesenchymal neoplasm, that is usually asymptomatic. Although benign, malignant transformation has been reported. A 59-year-old man presented with dyspepsia refractory to treatment with proton-pump inhibitor over 6 months. Esophagogastroduodenoscopy revealed a 30 mm subepithelial lesion in the distal gastric antrum, in contact with the pylorus, but biopsies were nonspecific. Upper endoscopic ultrasound revealed a well-defined submucosal echogenic lesion measuring 30 × 20 mm, without muscularis propria involvement. A fine-needle aspiration biopsy showed GGT features. En bloc endoscopic resection was performed using the submucosal tunneling endoscopic resection technique. The histopathological study of the specimen confirmed the diagnosis of a GGT with free margins. The patient remains symptom-free after a 9-month follow-up. We highlight the rare diagnosis of GGT and the possibility of curative en bloc endoscopic resection with submucosal tunneling endoscopic resection.

Clinicopathological Characteristics and Perioperative Treatment of Epstein-Barr Virus-Associated Gastric Cancer: A Retrospective Study.

The clinicopathological characteristics and perioperative treatment outcomes of patients with EBVaGC who underwent radical gastrectomy in Tianjin Medical University Cancer Hospital from September 2016 to May 2022 were retrospectively reviewed. Disease-free survival (DFS) was analyzed and Cox regression analysis was performed to identify risk factors. The study cohort included 128 patients with EBVaGC. Histologically, 126 (98.4%) patients had adenocarcinoma and only 2 (1.6%) had adenosquamous carcinoma. In addition, 18 (14.1%) had nerve invasion and 29 (22.7%) had vascular invasion. Notably, 41 (32.0%) patients had tumors in the proximal stomach and 69 (53.9%) had no lymph node metastasis. Proficient mismatch repair was confirmed in all 104 patients with available results. Overall, 16 (12.5%) patients received neoadjuvant therapy, 81 (63.3%) received adjuvant therapy, and 10 (7.8%) received perioperative immunotherapy combined with chemotherapy. In total, 22 patients experienced disease progression or had died. The 3-year DFS rate was 75.0%. DFS was relatively poorer for patients with advanced tumor (T) stage, lymph node (N) stage, disease stage, and vascular invasion. EBVaGC had unique clinicopathological characteristics and prognosis. Advanced T, N, and disease stages, in addition to vascular invasion, were predictive of poorer DFS. However, the efficacy of perioperative treatment of EBVaGC remains uncertain.

Persistence of activated anti-mesothelin hYP218 chimeric antigen receptor T cells in the tumour is associated with efficacy in gastric and colorectal carcinomas.

Patients with advanced gastric and colorectal cancers have limited treatment options. Since mesothelin is highly expressed in these tumour types, we evaluated the therapeutic benefits of anti-mesothelin hYP218 CAR T cells alone, and in combination with anti-PD1 antibody, pembrolizumab. GEPIA analysis was performed using human gastric (n=408) and colon cancer tumours (n=275) in TCGA database, to evaluate mRNA expression of mesothelin, compared to normal tissues. Mesothelin expression in gastric and colorectal cancer cell-lines (n=5) was analysed using flow cytometry. In vitro efficacy by hYP218 CAR T cells was tested by cytotoxicity and cytokine release assays. In vivo anti-tumour efficacy of hYP218 CAR T cells alone, and in combination with pembrolizumab, was evaluated in NSG mice bearing human gastric (HGC27) and colorectal (SW48) tumour xenografts. Additionally, hYP218 CAR-T cell persistence, activation and exhaustion marker-expression were studied. Mesothelin expression was significantly higher in gastric and colon cancer biopsies compared to normal tissues (p<.005). Mesothelin expression in gastric and colon cancer cell lines ranged from 10000 to 70000 molecules per cell. hYP218 CAR T cells demonstrated strong cytotoxic activity at low effector to target ratio, ranging from 0.24 to 1.0. In NSG mouse-models, hYP218 CAR T cells demonstrated anti-tumour efficacy and persisted in the tumour microenvironment in a functional state at day 40 posttreatment with expression of activation markers CD39 and CD69, increased production of IFN-γ and TNF-α and ability to kill tumour cells in vitro when isolated from tumours. There was increased PD1 expression. In combination with pembrolizumab, hYP218 CAR T cells led to slower tumour growth in NSG mice bearing large but not small HGC27 tumours. Anti-tumour efficacy of hYP218 CAR T cells is due to increased accumulation of activated CAR T cells in the tumour and combination with pembrolizumab resulted in improvement in anti-tumour activity of large established tumours. HIGHLIGHTS: Mesothelin expression is significantly higher in gastric and colorectal cancers than normal tissues. hYP218 CAR T cells demonstrate strong anti-tumour activity against mesothelin-positive gastric and colorectal carcinomas. Activated hYP218 CAR T cells persist in the tumour microenvironment and retain their cytotoxic activity. Addition of pembrolizumab in larger tumours enhance CAR T cell efficacy.

Utility of near-infrared fluorescent clip for the robot-assisted gastrectomy: Report of 2 cases (case series)

Introduction and importanceThe importance of preoperative tumor site marking has increased over the years, as the method of intraoperative primary lesion identification and determination of resection margins is one factor determining whether oncological safety and function-preserving gastrectomy are possible during surgery. We hypothesize that preoperative placement of the near-infrared fluorescent (NIRF) clip, ZEOCLIP FS, near the oral incision line of the gastric tumor will allow for Firefly recognition of the NIRF clip on da Vinci during surgery and easy determination of the tumor location and incision line. Hence, we report on two cases in which the procedure was performed. Case presentationCase 1: A 62-year-old woman was diagnosed with early gastric cancer of 35 mm in size located in the greater curvature of the gastric angle and underwent robot-assisted distal gastrectomy. NIRF clips were placed around the negative biopsy-confirmed area on the tumor's oral side by endoscopy on the day before surgery. The clips were identified intraoperatively in Firefly mode, and we performed gastrectomy without using an intraoperative endoscope. Case 2: A 60-year-old man was diagnosed with early gastric cancer 40 mm in size on the anterior wall of the gastric angle and underwent robot-assisted distal gastrectomy. Similarly, NIRF clips were placed around the site of negative biopsy confirmation the day before surgery. NIRF clips were identified, and we performed gastrectomy. Clinical discussionThe time taken to mark the gastric resection line after activating the Firefly imaging system was 120 and 154 s, respectively, and intraoperative endoscopy was not required. The advantage of our two-step method is that a surgeon can mark the clips the day before the surgery, even if they are not endoscopists. Increasing the recognition rate of fluorescent clips and preventing their remains are future issues. ConclusionBased on the results of the above two cases, ZEOCLIP FS is influential in determining the tumor's location and the resection line.

Identification and validation of CCN family genes to predict the prognosis in gastric cancer

BackgroundGastric cancer (GC) is a deadly malignancy with an ever-increasing incidence worldwide. The cellular communication network (CCN) family serves as matricellular proteins and exerts their various functions via regulating cell proliferation and differentiation. This study aimed to perform an integrated analysis of CCNs to predict the prognosis in GC.MethodsThe microarray datasets were obtained from Gene Expression Omnibus database to identify the differentially expressed genes between GC and non-tumor tissues. Functional enrichment and genetic alteration analysis revealed the biological functions and alteration status associated with CCNs. We analyzed the mRNA and protein expressions of CCN family in GC patients. Furthermore, the prognostic value of distinct CCN family members were analyzed using the Kaplan–Meier plotter database. Finally, the human gastric cancer cell lines were used for in vitro experiments to further validate the role of WISP1.Results26 genes were firstly identified to be significantly highly expressed in gastric tumor tissues. CCN family genes were identified to predict the prognosis in GC. Among the six CCNs, WISP1 is upregulated in GC tissues and its highly expression is associated with poor survival in GC patients. Moreover, a significant correlation is found between the expression of WISP1 and the pathological stage of patients with GC. Additionally, in vitro experiments demonstrated that WISP1 promotes the proliferation and invasive potential of GC cells, suggesting it may be a potential therapeutic target for GC.ConclusionsA comprehensive bioinformatic analysis of CCN genes provides new insights into the potential roles of this family in GC. Importantly, WISP1 may be a good prognostic predictor and a potential therapeutic target for GC.

Qingrexiaoji Recipe Regulates the Differentiation of M2 TAM via miR-29 in GC.

Gastric cancer, one of the most familiar adenocarcinomas of the gastrointestinal tract, ranks third in the world in cancer-related deaths. Traditional Chinese medicine can suppress the growth of tumors, and the underlying mechanism may be associated with the tumor microenvironment. Here, we investigated the anti-cancer effects of the Qingrexiaoji recipe on gastric cancer and the underlying molecular mechanism. An in vivo nude mouse model was established, and the expression of CD206, CD80, and M2 phenotype-related proteins (Arg-1, Fizz1) was obtained by flow cytometry and western blotting. The expressions of the M2 phenotype-related cytokines were examined by ELISA. Qingrexiaoji recipe inhibited gastric tumor growth and downregulated the expression of CD206, IFN-γ, IL-13, IL-4, and TNF-α in vivo. Qingrexiaoji recipe deceased M2 phenotypic polarization by upregulating microRNA (miR)-29a-3p level. Luciferase activity assays showed that HDAC4 is a potential target of miR-29a-3p. In cells co-transfected with HDAC4 siRNA and miR-29a-3p inhibitor and treated with IL-4 and Qingrexiaoji recipe, the miR-29a-3p inhibitorinduced increase of M2 phenotypic polarization was reversed. In summary, these results suggested that the Qingrexiaoji recipe regulated M2 macrophage polarization by regulating miR-29a-3p/HDAC4, providing a different and innovative treatment for gastric cancer.