World Journal of Gastrointestinal Oncology最新文献

{"title":"Roles of the tumor microenvironment in the resistance to programmed cell death protein 1 inhibitors in patients with gastric cancer.","authors":"Ren-Jie Xia, Xiao-Yu Du, Li-Wen Shen, Jian-Guo Ma, Shu-Mei Xu, Rui-Fang Fan, Jian-Wei Qin, Long Yan","doi":"10.4251/wjgo.v16.i9.3820","DOIUrl":"10.4251/wjgo.v16.i9.3820","url":null,"abstract":"<p><p>Despite the continuous developments and advancements in the treatment of gastric cancer (GC), which is one of the most prevalent types of cancer in China, the overall survival is still poor for most patients with advanced GC. In recent years, with the progress in tumor immunology research, attention has shifted toward immunotherapy as a therapeutic approach for GC. Programmed cell death protein 1 (PD-1) inhibitors, as novel immunosuppressive medications, have been widely utilized in the treatment of GC. However, many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy. To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy, to maximize the clinical activity of immunosuppressive drugs, and to elicit a lasting immune response, it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients. This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment, aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early diagnosis of esophageal cancer: How to put \"early detection\" into effect?","authors":"Suolang Pubu, Jun-Wen Zhang, Jian Yang","doi":"10.4251/wjgo.v16.i8.3386","DOIUrl":"10.4251/wjgo.v16.i8.3386","url":null,"abstract":"<p><p>This editorial comments on the article by Qu <i>et al</i> in a recent edition of <i>World Journal of Gastrointestinal Oncology</i>, focusing on the importance of early diagnosis in managing esophageal cancer and strategies for achieving \"early detection\". The five-year age-standardized net survival for esophageal cancer patients falls short of expectations. Early detection and accurate diagnosis are critical strategies for improving the treatment outcomes of esophageal cancer. While advancements in endoscopic technology have been significant, there seems to be an excessive emphasis on the latest high-end endoscopic devices and various endoscopic resection techniques. Therefore, it is imperative to redirect focus towards proactive early detection strategies for esophageal cancer, investigate the most cost-effective screening methods suitable for different regions, and persistently explore practical solutions to improve the five-year survival rate of patients with esophageal cancer.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Importance of diet and intestinal microbiota in the prevention of colorectal cancer - colonoscopy early screening diagnosis.","authors":"Miljana Z Jovandaric","doi":"10.4251/wjgo.v16.i8.3428","DOIUrl":"10.4251/wjgo.v16.i8.3428","url":null,"abstract":"<p><p>Colorectal cancer is a term used to describe colon and rectal cancer, which is the third most common type of cancer. A MEDLINE and PubMed search resulted in the inclusion of manuscripts written in the last 10 years, using keywords relevant to the topic of the manuscript. By analyzing the aim of the searched studies and manuscripts, adequate articles were included that described the stated problem. The frequency of colorectal cancer varies with climate, nutrition, and many other factors, primarily endogenous, hereditary, intestinal microbiome, as well as external factors, such as exposure of the individual to stress, and bad eating habits. Colon cancer and rectal cancer or colorectal cancer in general in the early stages of the disease, may not show symptoms or are barely noticeable. Colorectal cancer symptoms will most often not develop until the disease has progressed to stage 2 or beyond. Regular screening tests for colon or rectal cancer, especially colonoscopy, are recommended as part of a regular checkup for people aged 50 years or younger who are at high risk due to a family history of the disease or other cancers. Diet and colonoscopy as an early screening method play an important role in the prevention of colorectal cancer.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of vascular thrombus and clinicopathological factors in prognosis of gastric cancer: A retrospective cohort study.","authors":"Guo-Yue Chen, Ping Ren, Zhen Gao, Hao-Ming Yang, Yan Jiao","doi":"10.4251/wjgo.v16.i8.3436","DOIUrl":"10.4251/wjgo.v16.i8.3436","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is one of the most common malignant tumors in the world, and its prognosis is closely related to many factors. In recent years, the incidence of vascular thrombosis in patients with GC has gradually attracted increasing attention, and studies have shown that it may have a significant impact on the survival rate and prognosis of patients. However, the specific mechanism underlying the association between vascular thrombosis and the prognosis of patients with GC remains unclear.</p><p><strong>Aim: </strong>To analyze the relationships between vascular cancer support and other clinicopathological factors and their influence on the prognosis of patients with GC.</p><p><strong>Methods: </strong>This study retrospectively analyzed the clinicopathological data of 621 patients with GC and divided them into a positive group and a negative group according to the presence or absence of a vascular thrombus. The difference in the 5-year cumulative survival rate between the two groups was compared, and the relationships between vascular cancer thrombus and other clinicopathological factors and their influence on the prognosis of patients with GC were analyzed.</p><p><strong>Results: </strong>Among 621 patients with GC, the incidence of vascular thrombi was 31.7% (197 patients). Binary logistic regression analysis revealed that the degree of tumor differentiation, depth of invasion, and extent of lymph node metastasis were independent influencing factors for the occurrence of vascular thrombi in GC patients (<i>P</i> < 0.01). The trend of the <i>χ</i> ² test showed that the degree of differentiation, depth of invasion, and extent of lymph node metastasis were linearly correlated with the percentage of vascular thrombi in GC patients (<i>P</i> < 0.01), and the correlation between lymph node metastasis and vascular thrombi was more significant (<i>r</i> = 0.387). Univariate analysis revealed that the 5-year cumulative survival rate of the positive group was significantly lower than that of the negative group (46.7% <i>vs</i> 73.3%, <i>P</i> < 0.01). Multivariate analysis revealed that age, tumor diameter, TNM stage, and vascular thrombus were independent risk factors for the prognosis of GC patients (all <i>P</i> < 0.05). Further stratified analysis revealed that the 5-year cumulative survival rate of stage III GC patients in the thrombolase-positive group was significantly lower than that in the thrombolase-negative group (36.1% <i>vs</i> 51.4%; <i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>Vascular cancer status is an independent risk factor affecting the prognosis of patients with GC. The combination of vascular cancer suppositories and TNM staging can better judge the prognosis of patients with GC and guide more reasonable treatment.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting colorectal cancer with Herba Patriniae and Coix seed: Network pharmacology, molecular docking, and <i>in vitro</i> validation.","authors":"Cheng-Lei Wang, Bing-Wei Yang, Xin-Yan Wang, Xue Chen, Wei-Dong Li, Hao-Yu Zhai, Ying Wu, Mu-Yao Cui, Jia-He Wu, Qing-Hui Meng, Nan Zhang","doi":"10.4251/wjgo.v16.i8.3539","DOIUrl":"10.4251/wjgo.v16.i8.3539","url":null,"abstract":"<p><strong>Background: </strong>Herba Patriniae and Coix seed (HC) constitute a widely utilized drug combination in the clinical management of colorectal cancer (CRC) that is known for its diuretic, anti-inflammatory, and swelling-reducing properties. Although its efficacy has been demonstrated in a clinical setting, the active compounds and their mechanisms of action in CRC treatment remain to be fully elucidated.</p><p><strong>Aim: </strong>To identify the active, CRC-targeting components of HC and to elucidate the mechanisms of action involved.</p><p><strong>Methods: </strong>Active HC components were identified and screened using databases. Targets for each component were predicted. CRC-related targets were obtained from human gene databases. Interaction targets between HC and CRC were identified. A \"drug-ingredient-target\" network was created to identify the core components and targets involved. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to elucidate the key pathways involved. Molecular docking between core targets and key components was executed. <i>In vitro</i> experiments validated core monomers.</p><p><strong>Results: </strong>Nineteen active components of HC were identified, with acacetin as the primary active compound. The predictive analysis identified 454 targets of the active compounds in HC. Intersection mapping with 2685 CRC-related targets yielded 171 intervention targets, including 30 core targets. GO and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Molecular docking showed that acacetin exhibited an optimal interaction with <i>AKT1</i>, identifying <i>PI3K</i>, <i>AKT</i>, and <i>P53</i> as key genes likely targeted by HC during CRC treatment. Acacetin inhibited HT-29 cell proliferation and migration, as well as promoted apoptosis, <i>in vitro</i>. Western blotting analysis revealed increased <i>p53</i> and cleaved caspase-3 expression and decreased levels of <i>p-PI3K</i>, <i>p-Akt</i>, and survivin, which likely contributed to CRC apoptosis.</p><p><strong>Conclusion: </strong>Acacetin, the principal active compound in the HC pair, inhibited the proliferation and migration of HT-29 cells and promoted apoptosis through the PI3K/Akt/p53 signaling pathway.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jejunal sarcomatoid carcinoma: A case report and review of literature.","authors":"Qian Feng, Wei Yu, Jing-Hui Feng, Qiao Huang, Gui-Xiang Xiao","doi":"10.4251/wjgo.v16.i8.3723","DOIUrl":"10.4251/wjgo.v16.i8.3723","url":null,"abstract":"<p><strong>Background: </strong>Sarcomatoid carcinoma (SCA) of the jejunum is a rare and aggressive neoplasm affecting the smooth muscle cells of the jejunum. This study presents a recent case of jejunal SCA, detailing its diagnosis and treatment, thereby providing a reference for clinical practice.</p><p><strong>Case summary: </strong>A 65-year-old male presented to Yichang Central People's Hospital with a chief complaint of hemorrhoids. A computed tomography (CT) scan incidentally revealed multiple abnormal signals in the liver. Subsequent positron emission tomography/CT at Wuhan Union Hospital indicated malignant tumor progression, with a primary duodenal tumor and multiple metastases in the upper left abdomen. Intraoperatively, a large tumor was identified on the omentum. Histopathological and immunohistochemical analyses of the resected specimen confirmed the diagnosis of jejunal SCA. The patient received a combination therapy of sintilimab, nanoparticle albumin-bound paclitaxel, and anlotinib. Follow-up imaging demonstrated significant reduction of hepatic and peritoneal lesions. The patient has remained stable for over one year postoperatively.</p><p><strong>Conclusion: </strong>This case suggests that chemotherapy, immunotherapy, plus targeted therapy may represent an optimal treatment for intestinal SCA, meriting further investigation.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1.","authors":"Shin Woo Kang, Sung Hee Lim, Min-Ji Kim, Jeeyun Lee, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Seung Tae Kim","doi":"10.4251/wjgo.v16.i8.3521","DOIUrl":"10.4251/wjgo.v16.i8.3521","url":null,"abstract":"<p><strong>Background: </strong>Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, inhibits angiogenesis and reduces tumor growth. Serum VEGF-C, lactate dehydrogenase, and inflammatory markers have been reported as predictive markers related to bevacizumab treatment. Programmed cell death ligand 1 (PD-L1) could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.</p><p><strong>Aim: </strong>To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer (CRC) according to the expression of PD-L1.</p><p><strong>Methods: </strong>This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24, 2014 and February 28, 2022, at Samsung Medical Center (Seoul, South Korea). Analysis of patient data included evaluation of PD-L1 expression by the combined positive score (CPS). We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.</p><p><strong>Results: </strong>A total of 124 patients was included in this analysis. Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy. While 77% of patients received FOLFOX, 23% received FOLFIRI as backbone first-line chemotherapy. The numbers of patients with a PD-L1 CPS of 1 or more, 5 or more, or 10 or more were 105 (85%), 64 (52%), and 32 (26%), respectively. The results showed no significant difference in progression-free survival (PFS) and overall survival (OS) with bevacizumab treatment between patients with PD-L1 CPS less than 1 and those with PD-L1 CPS of 1 or more (PD-L1 < 1% <i>vs</i> PD-L1 ≥ 1%; PFS: <i>P</i> = 0.93, OS: <i>P</i> = 0.33), between patients with PD-L1 CPS less than 5 and of 5 or more (PD-L1 < 5% <i>vs</i> PD-L1 ≥ 5%; PFS: <i>P</i> = 0.409, OS: <i>P</i> = 0.746), and between patients with PD-L1 CPS less than 10 and of 10 or more (PD-L1 < 10% <i>vs</i> PD-L1 ≥ 10%; PFS: <i>P</i> = 0.529, OS: <i>P</i> = 0.568).</p><p><strong>Conclusion: </strong>Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression and significant roles of the long non-coding RNA CASC19/miR-491-5p/HMGA2 axis in the development of gastric cancer.","authors":"Li-Xiang Zhang, Pan-Quan Luo, Zhi-Jian Wei, A-Man Xu, Tao Guo","doi":"10.4251/wjgo.v16.i8.3559","DOIUrl":"10.4251/wjgo.v16.i8.3559","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a common malignant tumor, long non-coding RNA and microRNA (miRNA) are important regulators that affect tumor proliferation, metastasis and chemotherapy resistance, and thus participate in tumor progression. CASC19 is a new bio-marker which can promote tumor invasion and metastasis. However, the mechanism by which CASC19 affects the progression of GC through miRNA is not clear.</p><p><strong>Aim: </strong>To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC.</p><p><strong>Methods: </strong>To explore the expression and prognosis of CASC19 in GC through clinical samples, and investigate the effects of inhibiting CASC19 on the proliferation, migration, invasion and other functions of GC cells through cell counting Kit-8 (CCK-8), ethynyldeoxyuridine, Wound healing assay, Transwell, Western blot and flow cytometry experiments. The effect of miR-491-5p and HMGA2 in GC were also proved. The regulatory relationship between CASC19 and miR-491-5p, miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR. Then CCK-8, Transwell, Wound healing assay, flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis.</p><p><strong>Results: </strong>The expression level of CASC19 is related to the T stage, N stage, and tumor size of patients. Knockdown of the expression of CASC19 can inhibit the ability of proliferation, migration, invasion and EMT conversion of GC cells, and knocking down the expression of CASC19 can promote the apoptosis of GC cells. Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells, miR-491-5p mimics can inhibit EMT conversion, and promote the apoptosis of GC cells, while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells. The expression of HMGA2 in GC tissues is higher than that in adjacent tissues. At the same time, the expression level of HMGA2 is related to the N and T stages of the patients. Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells. Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p, thereby affecting the biological functions of GC.</p><p><strong>Conclusion: </strong>CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC. This axis may serve as a potential biomarker and therapeutic target of GC.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.","authors":"De-Gang Li, Jia-Peng Jiang, Fan-Ye Chen, Wei Wu, Jun Fu, Gong-He Wang, Yu-Bo Li","doi":"10.4251/wjgo.v16.i8.3585","DOIUrl":"10.4251/wjgo.v16.i8.3585","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal stromal tumors (GISTs) are typical gastrointestinal tract neoplasms. Imatinib is the first-line therapy for GIST patients. Drug resistance limits the long-term effectiveness of imatinib. The regulatory effect of insulin-like growth factor 2 (IGF2) has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.</p><p><strong>Aim: </strong>To further investigate the mechanism of IGF2 specific to GISTs.</p><p><strong>Methods: </strong>IGF2 was screened and analyzed using Gene Expression Omnibus (GEO: GSE225819) data. After IGF2 knockdown or overexpression by transfection, the phenotypes (proliferation, migration, invasion, apoptosis) of GIST cells were characterized by cell counting kit 8, Transwell, and flow cytometry assays. We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition (EMT)-associated proteins. We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.</p><p><strong>Results: </strong>Data from the GEO indicated that IGF2 expression is high in GISTs, associated with liver metastasis, and closely related to drug resistance. GIST cells with high expression of IGF2 had increased proliferation and migration, invasiveness and EMT. Knockdown of IGF2 significantly inhibited those activities. In addition, OE-IGF2 promoted GIST metastasis <i>in vivo</i> in nude mice. IGF2 activated IGF1R signaling in GIST cells, and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis. GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance. Moreover, 2-deoxy-D-glucose (a glycolysis inhibitor) treatment reversed IGF2 overexpression-mediated imatinib resistance in GISTs.</p><p><strong>Conclusion: </strong>IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lecithin-cholesterol acyltransferase is a potential tumor suppressor and predictive marker for hepatocellular carcinoma metastasis.","authors":"Yan Li, Li-Na Jiang, Bo-Kang Zhao, Mei-Ling Li, Yi-Yun Jiang, Yi-Si Liu, Shu-Hong Liu, Li Zhu, Xin Ye, Jing-Min Zhao","doi":"10.4251/wjgo.v16.i8.3651","DOIUrl":"10.4251/wjgo.v16.i8.3651","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide, and metastasis is the main cause of early recurrence and poor prognosis. However, the mechanism of metastasis remains poorly understood.</p><p><strong>Aim: </strong>To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC treatment.</p><p><strong>Methods: </strong>The candidate molecule lecithin-cholesterol acyltransferase (LCAT) was screened by gene microarray and bioinformatics analysis. The expression levels of LCAT in clinical cohort samples was detected by quantitative real-time polymerase chain reaction and western blotting. The proliferation, migration, invasion and tumor-forming ability were measured by Cell Counting Kit-8, Transwell cell migration, invasion, and clonal formation assays, respectively. Tumor formation was detected in nude mice after <i>LCAT</i> gene knockdown or overexpression. The immunohistochemistry for Ki67, E-cadherin, N-cadherin, matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on HCC. Gene set enrichment analysis (GSEA) on various gene signatures were analyzed with GSEA version 3.0. Three machine-learning algorithms (random forest, support vector machine, and logistic regression) were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO databases.</p><p><strong>Results: </strong><i>LCAT</i> was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC tissues. LCAT was significantly downregulated in HCC tissues, which is correlated with recurrence, metastasis and poor outcome of HCC patients. Functional analysis indicated that LCAT inhibited HCC cell proliferation, migration and invasion both <i>in vitro</i> and <i>in vivo</i>. Clinicopathological data showed that LCAT was negatively associated with HCC size and metastasis (HCC size ≤ 3 cm <i>vs</i> 3-9 cm, <i>P</i> < 0.001; 3-9 cm <i>vs</i> > 9 cm, <i>P</i> < 0.01; metastatic-free HCC <i>vs</i> extrahepatic metastatic HCC, <i>P</i> < 0.05). LCAT suppressed the growth, migration and invasion of HCC cell lines <i>via</i> PI3K/AKT/mTOR signaling. Our results indicated that the logistic regression model based on LCAT, TNM stage and the serum level of α-fetoprotein in HCC patients could effectively predict high metastatic risk HCC patients.</p><p><strong>Conclusion: </strong><i>LCAT</i> is downregulated at translational and protein levels in HCC and might inhibit tumor metastasis <i>via</i> attenuating PI3K/AKT/mTOR signaling. LCAT is a prognostic marker and potential therapeutic target for HCC.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}