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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

Science China Life Sciences 2025年第1期 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute department of gastrointestinal Cancer center Peking University Cancer Hospital & Institute department of Liver Surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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Science China Life Sciences 2025年第1期 263-271页

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian Cancer Institute Linzhou Cancer Hospital center for Disease Control and Prevention of Sheyang County department of Cancer Prevention and Control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University Luoshan center for Disease Control and Prevention Office for Cancer Control and Research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer（GC） in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates（CIRs） of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic（atrophic gastritis/intestinal metaplasia） and neoplastic lesions（low-grade/high-grade dysplasia）, respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients（≥3 risk factors） with non-neoplastic lesions showed higher GC risks（adjusted HR=7.73, 95%CI: 4.29–13.92）, and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions（aHR=3.07, 95%CI: 1.67–5.64） and high-risk patients with mild lesions（aHR=7.29, 95%CI: 3.58–14.86） showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

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Prognostic value of site-specific metastases in pancreatic adenocarcinoma: A Surveillance Epidemiology and End Results database analysis

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World Journal of Gastroenterology 2017年第10期23卷 1872-1880页

作者： Hani Oweira Ulf Petrausch Daniel Helbling Jan Schmidt Meinrad Mannhart Arianeb Mehrabi Othmar Schob Anwar Giryes Michael Decker Omar Abdel-Rahman Surgical center Zurich-Swiss cancer institute department of General Visceral and Transplant SurgeryUniversity of Heidelberg Swiss tumor immunology institute gastrointestinal tumor center Zurich Surgical center Zurich-Hirslanden Hospital Zurich department of Oncology center of Zug Zentrum für integrative Onkologie clinical Oncology department Faculty of MedicineAin Shams University

To evaluate the prognostic value of site-specific metastases among patients with metastatic pancreatic carcinoma registered within the Surveillance, Epidemiology and End Results (SEER) *** database (2010-2013) has been queried through SEER*Stat program to determine the presentation, treatment outcomes and prognostic outcomes of metastatic pancreatic adenocarcinoma according to the site of metastasis. In this study, metastatic pancreatic adenocarcinoma patients were classified according to the site of metastases (liver, lung, bone, brain and distant lymph nodes). We utilized chi-square test to compare the clinicopathological characteristics among different sites of metastases. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. We employed Cox proportional model to perform multivariate analyses of the patient population; and accordingly hazard ratios with corresponding 95%CI were generated. Statistical significance was considered if a two-tailed P value tumor and surgery to the metastatic disease were associated with better overall survival and pancreatic cancer-specific *** adenocarcinoma patients with isolated liver metastases have worse outcomes compared to pat

关键词： Pancreatic cancer Liver metastases Lung metastases Bone metastases Surveillance Epidemiology and End Results database

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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang department of Oncology The Fifth Medical Center of Chinese PLA General Hospital department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of Translational Research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteractiontumor-infiltrating CD8+T cells in nsqNSCLCs（P=0.040） and sqNSCLCs（P=0.014）,*** the POPLAR/OAK cohort,nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel(hazard ratio（HR）=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del（HR=1.05,P=0.64）.Conversely,sqNSCLCs without LRP1B-del benefited more from atezolizumab（HR=0.60,P=0.002） than those with LRP1B-del（HR=1.30,P=0.31）.Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy *** findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

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Depression and anxiety levels in therapy-nave patients with inflammatory bowel disease and cancer of the colon

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World Journal of Gastroenterology 2007年第3期13卷 438-443页

作者： Branislav R Filipovi Branka F Filipovi Mirko Kerkez Nikola Milini Tomislav Ran■elovi Institute of Anatomy School of Medicine Belgrade Clinical and Hospital center "Be■anijska Kosa" Department of Gastroenterology Belgrade Serbia department of gastrointestinal Surgery Clinical Center of Serbia Serbia department of gastrointestinal Surgery Clinical and Hospital Center "Be■anijska Kosa" Belgrade Serbia

AIM: To assess whether depression and anxiety are more expressed in patients with the first episode of inflammatory bowel disease (IBD) than in individuals with newly discovered cancer of the colon (CCa). METHODS: A total of 32 patients with IBD including 13 males and 19 females, aged 27 to 74, and 30 patients with CCa including 20 males and 10 females, aged 39-78, underwent a structured interview, which comprised Hamilton’s Depression Rating Inventory, Hamilton’s Anxiety Rating Inventory and Paykel’s Stressful Events Rating Scale. RESULTS: Patients of the IBD group expressed both depression and anxiety. Depressive mood, sense of guilt, psychomotor retardation and somatic anxiety were also more pronounced in IBD patients. The discriminant function analysis revealed the total depressive score was of high importance for the classification of a newly diagnosed patient into one of the groups. CONCLUSION: Newly diagnosed patients with IBD have higher levels of depression and anxiety. Moreover, a psychiatrist in the treatment team is advisable from the beginning.

关键词： Crohn's disease Ulcerative colitis Colon cancer Mood disorder

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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life Sciences 2025年第1期 204-218页

作者： Chen Xiong Hong Ling Yingdan Huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou Fudan University Shanghai Cancer center and Institutes of Biomedical Sciences Fudan University department of Oncology Shanghai Medical CollegeFudan University department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

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Comparing effectiveness and safety of paclitaxel plus raltitrexed vs. paclitaxel alone in second-line palliative chemotherapy for metastatic gastric adenocarcinoma: A randomized phase Ⅱ clinical trial

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Cancer Biology & Medicine 2023年第9期20卷 682-688页

作者： Xiaoying Zhao Zhiyu Chen Xiaowei Zhang Xiaodong Zhu Wen Zhang Lixin Qiu Chenchen Wang Mingzhu Huang Zhe Zhang Wenhua Li Lei Yang Weijian Guo department of gastrointestinal Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Shanghai Medical College Fudan UniversityShanghai 200032China department of Medical Oncology Nantong Tumor HospitalNantong 226006China

Objective:Paclitaxel(P)is a standard second-line chemotherapy in the treatment of advanced gastric *** study compared the clinical outcome of a paclitaxel plus raltitrexed(RP)regimen as second-line treatment in metastatic gastric cancer(MGC)***:An open,randomized,multi-center phase Ⅱ clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP[raltitrexed(3 mg/m^(2)on day 1)and paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]or P[paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]as 2nd-line *** primary endpoint was progression-free survival(PFS).The secondary endpoints were the overall response rate(ORR),overall survival(OS),and ***:PFS had a tendency to be prolonged with RP compared to P(2.7 months vs.1.7 months;P=0.148).OS was also prolonged with RP compared to P(10.2 months vs.6.1 months;P=0.140).The ORR was equal in the RP and P groups(6.8%and 4.0%;P=0.72).The disease control rate(DCR)in the RP and P groups was 56.2%and 36.0%,*** 3-4 treatment-related adverse events occurred in 36.2%(RP)and 28.2%(P)of *** grade 3-4 toxicities for RP and P were neutropenia(11.0%and 4.0%),anemia(1.4%and 4.0%),and thrombocytopenia(1.4%and 5.3%),and all grades of peripheral neurotoxicity(12.3%vs.17.3%).All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels(27.4%and 14.1%).Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement,the OS of the RP regimen was longer(P=0.05).Conclusions:Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS,especially among patients with ascites or peritoneal involvement,which warrants confirmation using larger sample studies.

关键词： Gastric adenocarcinoma raltitrexed paclitaxel second-line palliative chemotherapy

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Impact of frailty on short-term postoperative outcomes in patients undergoing colorectal cancer surgery:A systematic review and meta-analysis

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World Journal of gastrointestinal Surgery 2024年第3期16卷 893-906页

作者： Yao Zhou Xiao-Lei Zhang Hong-Xia Ni Tian-Jing Shao Ping Wang department of Operating Room Affiliated Tumor Hospital of Nantong University&Nantong Tumor HospitalNantong 226361Jiangsu ProvinceChina department of gastrointestinal Surgery The Affiliated Tumor Hospital of Nantong University&Nantong Tumor HospitalNantong 226361Jiangsu ProvinceChina

BACKGROUND Colorectal cancer is a major global health challenge that predominantly affects older *** management,despite advancements,requires careful consideration of preoperative patient status for optimal *** To summarize existing evidence on the association of frailty with short-term postoperative outcomes in patients undergoing colorectal cancer *** A literature search was conducted using PubMed,EMBASE and Scopus databases for observational studies in adult patients aged≥18 years undergoing planned or elective colorectal surgery for primary carcinoma and/or secondary *** studies that conducted frailty assessment using recognized frailty assess-ment tools and had a comparator group,comprising nonfrail patients,were *** effect sizes were reported as weighted mean difference or relative risk(RR)with 95%confidence intervals(CIs).RESULTS A total of 24 studies were *** with nonfrail patients,frailty was associated with an increased risk of mortality at 30 d(RR:1.99,95%CI:1.47-2.69),at 90 d(RR:4.76,95%CI:1.56-14.6)and at 1 year(RR:5.73,95%CI:2.74-12.0)of follow *** patients had an increased risk of any complications(RR:1.81,95%CI:1.57-2.10)as well as major complications(Clavien-Dindo classification grade≥III)(RR:2.87,95%CI:1.65-4.99)compared with the control *** risk of reoperation(RR:1.18,95%CI:1.07-1.31),readmission(RR:1.70,95%CI:1.36-2.12),need for blood transfusion(RR:1.67,95%CI:1.52-1.85),wound complications(RR:1.49,95%CI:1.11-1.99),delirium(RR:4.60,95%CI:2.31-9.16),risk of prolonged hospitalization(RR:2.09,95%CI:1.22-3.60)and discharge to a skilled nursing facility or rehabilitation center(RR:3.19,95%CI:2.0-5.08)was all higher in frail *** Frailty in colorectal cancer surgery patients was associated with more complications,longer hospital stays,higher reoperation risk,and increased *** frailty assessment appears crucial for tailored surgical managem

关键词： Frailty Frail adults Colorectal surgery Colorectal cancer Complications Mortality Survival Slinical outcomes Meta-analysis

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Diagnosis and management of choledochal cyst: 20 years of single center experience

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World Journal of Gastroenterology 2014年第22期20卷 7061-7066页

作者： Nabil Gadelhak Ahmed Shehta Hosam Hamed department of Surgery Gastrointestinal Surgical CenterMansoura UniversityManoura 35516DakahleyyaEgypt

We report the first case series from Africa and the Middle East on choledochal cyst, a disease which shows significant geographical distribution with high incidence in the Asian population. In this study, the epidemiological data of the patients are presented and analyzed. Attention was paid to diagnostic imaging and its accuracy in the diagnosis and classification of choledochal cyst. Most cases of choledochal cyst disease have type I and IV-A cysts according to the Todani classification system, which support the etiological theories of choledochal cyst, especially Babbitt’s theory of the anomalous pancreaticobiliary duct junction, which are clearly stated. The difficulties and hazards of surgical management and methods used to avoid operative complications are clarified. Early and late postoperative complications are also included. This study should be followed by multicenter studies throughout Egypt to help assess the incidence of choledochal cysts in one of the largest populations in Africa and the Middle East.

关键词： Choledochal cyst Hepatic cyst Hepaticojejunostomy Caroli disease Hepatectomy

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Laparoscopic radical resection for situs inversus totalis with colonic splenic flexure carcinoma:A case report

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World Journal of Clinical Cases 2022年第16期10卷 5435-5440页

作者： Zi-Ling Zheng Shou-Ru Zhang Hao Sun Mao-Cai Tang Jing-Kun Shang department of gastrointestinal Cancer center Chongqing University Cancer HospitalChongqing 400030China

BACKGROUND Situs inversus totalis(SIT)is a rare group of congenital developmental malformations in the clinical setting,with all organs in the chest and abdomen existing in a mirror image reversal of their normal *** reports have described laparoscopic surgery for colorectal cancer in patients with SIT,and it is considered difficult even for an experienced surgeon because of the mirror *** present a case report of laparoscopic radical resection of a colonic splenic flexure carcinoma in a patient with *** SUMMARY A 72-year-old male was referred to our hospital with colonic splenic flexure carcinoma,and computed tomography showed that all the organs in the chest and abdomen were *** hemicolectomy with complete mesocolic excision was safely *** operating surgeon stood on the patient’s left side,which is opposite of the normal *** Abdominal computed tomography is an effective method for diagnosing SIT preoperatively in patients with colonic splenic flexure *** radical resection is difficult,but it is well established and *** surgeon should stand in the opposite position and perform backhand operations.

关键词： Situs inversus totalis Colonic splenic flexure carcinoma Laparoscopic radical resection Computed tomography Case report

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