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Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1564-1577页

作者： Sai-Nan Li Shan Yang Hao-Qi Wang Tian-Li Hui Meng Cheng Xi Zhang Bao-Kun Li Gui-Ying Wang The First department of surgery The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina The Second department of surgery The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina department of General surgery The Second Hospital of Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality *** to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient *** noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain *** To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this *** Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin *** bioinformatics tools were employed to elucidate molecular *** expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain *** assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA *** between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream ***,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy *** LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)*** was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 *** expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing *** RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of *** PRNT/ZNF184

关键词： Colorectal cancer Oxaliplatin resistance Prion protein testis specific Zinc finger protein 184 Homeodomain interacting protein kinase 2

High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 787-797页

作者： Peng-Yang Zhou De-Xiang Zhu Yi-Jiao Chen Qing-Yang Feng Yi-Hao Mao Ao-Bo Zhuang Jian-Min Xu department of General surgery Zhongshan Hospital Fudan UniversityShanghai 200032China

BACKGROUND Patatin like phospholipase domain containing 8(PNPLA8)has been shown to play a significant role in various cancer *** studies have focused on its roles as an antioxidant and in lipid ***,the role of PNPLA8 in colorectal cancer(CRC)progression is *** To explore the prognostic effects of PNPLA8 expression in *** A retrospective cohort containing 751 consecutive CRC patients was ***8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive *** patients were divided into high and low PNPLA8 expression groups based on the cut-off va-lues,which were calculated by X-tile *** prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression *** over-all survival(OS)rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank *** PNPLA8 expression was significantly associated with distant metastases in our cohort(P=0.048).CRC patients with high PNPLA8 expression indicated poor OS(median OS=35.3,P=0.005).CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter *** patients with left-sided colon and rectal cancer,the survival curves of two PN-PLA8-expression groups showed statistically significant *** analysis also confirmed that high PNPLA8 expression was an independent prog-nostic factor for overall survival(hazard ratio HR=1.328,95%CI:1.016-1.734,P=0.038).

关键词： Biomarker Colorectal cancer Expression level Overall survival Patatin like phospholipase domain containing 8 Prognosis

New anti-mesenteric delta-shaped stapled anastomosis: Technical report with short-term postoperative outcomes in patients with Crohn’s disease

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World Journal of Gastrointestinal surgery 2024年第8期16卷 2592-2601页

作者： Jong Lyul Lee Yong Sik Yoon Hyun Gu Lee Young Il Kim Min Hyun Kim Chan Wook Kim In Ja Park Seok-Byung Lim Chang Sik Yu Division of Colon and Rectal surgery Department of SurgeryUniversity of Ulsan College of MedicineAsan Medical CenterSeoul 05505South Korea department of surgery Gangdong Kyung Hee University HospitalSeoul 05278South Korea

BACKGROUND Medical treatment for Crohn’s disease(CD)has continuously improved,which has led to a decrease in surgical recurrence *** these advancements,25%of patients will undergo repeat intestinal *** of CD com-monly occurs on the mesentery side of the anastomosis *** To compare the new anti-mesenteric side-to-side delta-shaped stapled anasto-mosis(DSA)with the conventional stapled functional end-to-end anastomosis(CSA).METHODS This retrospective study included CD patients who underwent ileo-ileal or ileo-colic anastomosis between January 2020 and December *** DSA technique employed a stapler to maintain the concept of anti-mesentery side-to-side ana-stomosis by performing a 90°vertical closure of the open window compared with the CSA *** the corner where the open window is closed,the DSA avoids forming a pouch and creates an anastomosis resembling a delta shape within the intestinal *** compared demographics,preoperative condition,operative findings,and operative outcomes for the two *** The study included 175 patients,including 92 in the DSA group and 83 in the CSA *** two groups were similar in baseline characteristics,preoperative medical treatment,and operative findings except for the Montreal classification *** 30-days postoperative complication rate was signi-ficantly lower in the DSA group compared with the CSA group(16.3%vs 32.5%,P=0.009).Ileus incidence was significantly lower in the DSA group than in the CSA group(4.3%vs 14.5%,P=0.033),and the hospital stay was shorter in the DSA group than in the CSA group(5.67±1.53 days vs 7.39±3.68 days,P=0.001).CONCLUSION The DSA technique was feasible and showed comparable postoperative outcomes with lower short-term complic-ations compared with the CSA *** studies on CD recurrence and long-term complications are warranted.

关键词： Crohn’s disease surgery Anastomosis Complication Recurrence

OPA3 overexpression modulates lipid droplet production and sensitizes colorectal cancer cells to bevacizumab treatment

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BIOCELL 2024年第6期48卷 971-980页

作者： HONGBIAO WU DONGFANG LIU department of Colorectal and Anal surgery Ningbo First HospitalNingbo315010China

Background:Colorectal cancer(CRC)represents a substantial risk to public ***,theﬁrst US FDA-approved antiangiogenic drug(AAD)for human CRC treatment,faces resistance in *** role of lipid metabolism,particularly through OPA3-regulated lipid droplet production,in overcoming this resistance is under ***:The protein expression pattern of OPA3 in CRC primary/normal tissues was evaluated by bioinformatics ***3-overexpressed SW-480 and HCT-116 cell lines were established,and bevacizumab resistance and OPA3 effects on cell malignancy were ***3 protein/mRNA expression and lipid droplet-related genes were measured with Western blot and ***3 subcellular localization was detected using immunoﬂ*** and apoptosis were assessed via colony formation andﬂow *** formation assays were conducted to assess the angiogenic potential of human umbilical vein endothelial cells(HUVECs).Lipid analysis was used to measure the phosphatidylcholine(PC)and lysophosphatidylcholine(LPC)levels in CRC ***:Bioinformatics analysis revealed that OPA3 was downregulated in *** of OPA3 inhibited CRC cell proliferation,stimulated apoptosis,and suppressed the angiogenic ability of ***3 effectively reversed the resistance of CRC cells to bevacizumab and decreased lipid droplet production in CRC ***,OPA3 reversed the bevacizumab-induced lipid droplet production in CRC cells,thereby increasing CRC cell sensitivity to bevacizumab ***:This study suggests that OPA3 modulates lipid metabolism in CRC cells and reduces resistance to bevacizumab in CRC ***,OPA3 may be a potential therapeutic target against the AAD resistance in CRC.

关键词： Colorectal cancer OPA3 Bevacizumab Lipid droplet Antiangiogenic drug

Double role of depression in gastric cancer:As a causative factor and as consequence

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World Journal of Gastroenterology 2024年第10期30卷 1266-1269页

作者： Grigorios Christodoulidis Koumarelas Konstantinos-Eleftherios Kouliou Marina-Nektaria department of General surgery University Hospital of LarissaLarissa 41110Greece

In this editorial we comment on the article“Hotspots and frontiers of the rela-tionship between gastric cancer and depression:A bibliometric study”.Gastric cancer(GC)is a common malignancy in the digestive system with increased mortality and morbidity rates *** treatments,such as gastrectomy,negatively impact patients'quality of life and beyond the physical strain,GC patients face psychological challenges,including anxiety and *** prevalence of depression can be as high as 57%,among gastrointestinal cancer *** to the advancements in treatment effectiveness and increased 5-year overall survival rates,attention has shifted to managing psychological ***,the significance of managing the depression doesn’t lie solely in the need for a better psychological *** leads to chronic stress acti-vating the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis,leading release of catecholamines inducing tumor proliferation,migration,and metastasis,contributing to GC *** dysregulation of neurotrans-mitters and the involvement of various signaling pathways underscore the complex interplay between depression and *** strategies are required to address the psychological aspects of GC,including region-specific interventions and increased monitoring for *** the intricate relationship between depression and GC progression is essential for developing effective therapeutic strategies and improving overall outcomes for patients facing this complex *** this Editorial we delve into double role of depression in the pathogenesis of GC and as a complication of it.

关键词： Gastric cancer Depression Anxiety Chronic stress Pathogenesis of gastric cancer

Immune signature of small bowel adenocarcinoma and the role of tumor microenvironment

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World Journal of Gastroenterology 2024年第8期30卷 794-798页

作者： Grigorios Christodoulidis Marina Nektaria Kouliou Konstantinos Eleftherios Koumarelas department of General surgery University Hospital of LarissaLarissa 41110Greece

In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such *** detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor *** involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor *** are linked to genetic disorders and risk factors,including chronic inflammatory *** unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable *** cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic *** instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to *** presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI *** tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.

关键词： Programmed cell death 1 Programmed cell death-ligand 1 Programmed death ligand Small bowel adenocarcinoma Tumor infiltrating lymphocytes Tumor microenvironment Microsatellite instability

Options and survival benefits of conversion therapy for unresectable hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第18期30卷 2479-2481页

作者： Wong Hoi She Tan To Cheung department of surgery The University of Hong KongHong Kong 999077China

In the study by Wu et al,patients with unresectable hepatocellular carcinoma were subjected to transarterial chemoembolization(TACE)as a conversion therapy in order to render their tumors suitable for resection.A nomogram was devised and shown to be effective in predicting the survival of these *** of the results,however,is questionable since the study subjects consisted of patients who had resection after TACE while excluding patients with the same disease but not suitable for *** can be considered to be an option for conversion ***,markers for determining responses to a conversion therapy and for guiding the decision between TACE and sequential immunotherapy have been *** question of whether effective conversion therapy can truly enhance overall survival remains unanswered.

关键词： Conversion therapy Immunotherapy Liver resection Survival Transarterial chemoembolization Unresectable hepatocellular carcinoma

Revolutionizing gastric cancer treatment:The potential of immunotherapy

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World Journal of Gastroenterology 2024年第4期30卷 286-289页

作者： Grigorios Christodoulidis Konstantinos Eleftherios Koumarelas Marina Nektaria Kouliou department of General surgery University Hospital of LarissaLarissa 41110Greece

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual *** in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus ***,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited *** advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted *** immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific *** this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

关键词： Immunotherapy Adaptive immunotherapy Tumor vaccines Chimeric antigen receptor therapy Tumor-infiltrating lymphocytes therapy Natural killer therapy Cytokine-induced killer therapy Engineered T cell receptor therapy Immune checkpoint inhibitors

Chronic active and atrophic gastritis as significant contributing factor to the development of gastric cystica profunda

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World Journal of Gastroenterology 2024年第17期30卷 2308-2310页

作者： Veronika Papp Pál Miheller department of surgery Transplantation and GastroenterologySemmelweis UniversityBudapest 1082Hungary

Gastric cystica profunda(GCP)is an uncommon but underestimated gastric *** precancerous potential determines its *** addition to previous mucosa injury due to operations,biopsy or polypectomy,chronic active and atrophic gastritis may also lead to the development of *** carefully examining the stomach and taking biopsy samples from the susceptible regions,the stage of atrophy can be *** atrophic gastritis is a risk factor for cancer evolvement and it can also contribute to GCPs *** frequently occur close to early gastric cancers(EGCs)or EGC can arise from the cystic *** resection is an effective and minimally invasive treat-ment in GCP.

关键词： Gastric cystica profunda Chronic active gastritis Atrophic gastritis Operative Link for Gastritis Assessment staging Early gastric cancer Endoscopic resection