Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

BACKGROUND 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.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS 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.RESULTS 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,OEIGF2 promoted GIST metastasis in vivo 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 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

Preoperative blood markers and intra-abdominal infection after colorectal cancer resection

BACKGROUND Colorectal cancer(CRC)has one of the highest morbidity and mortality rates among digestive tract tumors.Intra-abdominal infection(IAI)is a common postoperative complication that affects the clinical outcomes of patients with CRC and hinders their rehabilitation process.However,the factors influencing abdominal infection after CRC surgery remain unclear;further,prediction models are rarely used to analyze preoperative laboratory indicators and postoperative complications.AIM To explore the predictive value of preoperative blood markers for IAI after radical resection of CRC.METHODS The data of 80 patients who underwent radical resection of CRC in the Anorectal Surgery Department of Suzhou Hospital affiliated with Anhui Medical University were analyzed.These patients were categorized into IAI(n=15)and non-IAI groups(n=65)based on whether IAI occurred.Influencing factors were compared;general data and laboratory indices of both groups were identified.The relationship between the indicators was assessed.Further,a nomogram prediction model was developed and evaluated;its utility and clinical applic-ability were assessed.RESULTS The risk factors for IAI after radical resection of CRC were neutrophil-lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),systemic immune-inflammation index(SII),and carcinoembryonic antigen(CEA)levels.NLR was correlated with PLR and SII(r=0.604,0.925,and 0.305,respectively),while PLR was correlated with SII(r=0.787).The nomogram prediction model demonstrated an area under the curve of 0.968[95%confidence interval(CI):0.948-0.988]in the training set(n=60)and 0.926(95%CI:0.906-0.980)in the validation set(n=20).The average absolute errors of the calibration curves for the training and validation sets were 0.032 and 0.048,respectively,indicating a good model fit.The decision curve analysis curves demonstrated high net income above the 5%threshold,indicating the clinical practicality of the model.CONCLUSION The nomogram model constructed using NLR,PLR,SII,and CEA levels had good accuracy and reliability in predicting IAI after radical resection of CRC,potentially aiding clinical treatment decision-making.

Effect of immunotherapy combined with intravenous chemotherapy on the tumor load,immune function and cancer cell proliferation activity in patients with advanced colon cancer

Objective: To study the effect of immunotherapy combined with intravenous chemotherapy on the tumor load, immune function and cancer cell proliferation activity in patients with advanced colon cancer. Methods: A total of 90 patients with advanced colon cancer who were treated in Second People's Hospital of Yibin between December 2014 and January 2017 were collected and divided into control group (n=45) and observation group (n=45) by random number table. Control group received routine intravenous chemotherapy, and the observation group received immunotherapy combined with intravenous chemotherapy. The levels of specific tumor markers and Th17/Treg cytokines in serum as well as proliferation gene expression in the lesion tissue were determined. Results: Before treatment, the differences in levels of specific tumor markers and Th17/Treg cytokines in serum as well as proliferation gene expression in lesion tissue were not statistically significant between the two groups. After treatment, PTN, CCSA-1, IL-17 and IL-23 levels in serum as well as GTPBP4 and PIK3CB mRNA expression in lesion tissue of both groups of patients were lower than those before treatment while IL-10 and IL-35 levels in serum as well as FAM96B, MS4A12 and FRAT1 mRNA expression in lesion tissue were higher than those before treatment, and PTN, CCSA-1, IL-17 and IL-23 levels in serum as well as GTPBP4 and PIK3CB mRNA expression in lesion tissue of observation group were lower than those of control group while IL-10 and IL-35 levels in serum as well as FAM96B, MS4A12 and FRAT1 mRNA expression in lesion tissue were higher than those of control group. Conclusion: Immunotherapy combined with intravenous chemotherapy can effectively reduce the tumor load, optimize cellular immune function and inhibit tumor cell proliferation in patients with advanced colon cancer.