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Genomic characterization of peritoneal lavage cytology-positive gastric cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 66-77页

作者： Zhouqiao Wu Tingfei Gu Changxian Xiong jinyao Shi jingpu Wang Ting Guo Xiaofang Xing Fei Pang Ning He Rulin Miao Fei Shan Yuan Zhou Ziyu Li jiafu ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Department of Biomedical Informatics Department of Physiology and PathophysiologyCenter for Noncoding RNA MedicineMOE Key Lab of Cardiovascular SciencesSchool of Basic Medical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China

Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.Results: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

关键词： Cytology gastric carcinoma peritoneal metastasis whole exome sequencing

Current status and perspectives of conversion therapy for advanced gastric cancer

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Chinese Journal of Cancer Research 2022年第2期34卷 109-114页

作者： Heli Yang Ke ji jiafu ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Center of Gastrointestinal CancerPeking University Cancer Hospital&InstituteBeijing 100142China

The concept and strategy of advanced gastric cancer treatment have gradually undergone profound changes with the in-depth understanding of the biology and heterogeneous characteristics of gastric cancer.Moreover,the development and application of new anticancer drugs,including chemotherapy drugs,molecularly targeted drugs and immunotherapy drugs for advanced gastric cancer are reported.The connotation of conversion therapy refers to the unresectable or borderline resectable tumors for surgical technical and/or oncological reasons,after active and effective chemotherapy and other comprehensive treatment,the primary gastric lesions can be reduced to a lower stage,while the metastatic lesions can be effectively controlled,to achieve R0 resection and improve the long-term survival rate.Current promising research results of conversion therapy are mostly from single-arm phase II clinical studies with small samples or retrospective studies.Conversion therapy still faces many challenges,including limited diagnostic and assessment methods,insufficient evidence of highly effective treatment regimens,difficulty in clarifying surgical indications,etc.Therefore,the integrated conversion therapy for advanced gastric cancer needs to be carried out with the close cooperation of a multidisciplinary team.Prospective,multi-center randomized controlled trial studies should be conducted in the future,and precision medicine such as molecular biology should be combined to provide better anticancer drug regimens and higher-level clinical evidence for conversion therapy of advanced gastric cancer.

关键词： Gastric cancer advanced conversion therapy multidisciplinary team

PTPRD/PTPRT mutation correlates to treatment outcomes of immunotherapy and immune landscape in pan-cancers

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Chinese Journal of Cancer Research 2023年第3期35卷 316-330页

作者： Gangjian Wang Xin ji Haojie Wang Xiaohuan Tang Xiaofang Xing jiafu ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100101China

Objective: PTPRD and PTPRT are phosphatases of the JAK-STAT pathway related to immunotherapy.However, the role and mechanism of PTPRD and PTPRT mutations in multiple cancers remains unclear.Methods: Clinical data and PTPRD/PTPRT mutation information from 12 cohorts were collected and classified as a discovery cohort and three validation cohorts. The association between PTPRD/PTPRT mutations and immunotherapeutic efficacy was analyzed. Then, the association between PTPRD/PTPRT mutation and immune profiles was analyzed using The Cancer Genome Atlas(TCGA) cohort.Results: A total of 2,392 patients across 20 cancer types were included in this study. Our results showed that patients harboring PTPRD/PTPRT mutation, especially co-mutations, had a significantly elevated response rate to immunotherapy in multiple cancers. Patients with PTPRD/PTPRT mutation had a higher objective response rate(ORR)(P=0.002), longer overall survival(OS)(P=0.005) and progression-free survival(PFS)(P=0.038).Importantly, the above findings were further verified in validation cohorts. In addition, we found that the PTPRD/PTPRT co-mutations(co-mut) subgroup exhibited an immune-activated phenotype, the wild-type subgroup tended to have an immune-desert phenotype, and the uni-mutation(uni-mut) subgroup might have an immune-mixed phenotype. Our further analyses suggested that combining programmed cell death ligand 1(PDL1) expression and PTPRD/PTPRT mutation can be used to screen patients who may benefit from immunotherapy.Conclusions: PTPRD/PTPRT mutation could serve as a potential predictive biomarker for cancer immunotherapy.

关键词： PTPRD PTPRT immune microenvironment immunotherapy biomarker

Comments on National guidelines for diagnosis and treatment of gastric cancer 2022 in China(English version)

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Chinese Journal of Cancer Research 2022年第5期34卷 453-455页

作者： jiahui Chen Zhaode Bu jiafu ji Department of Gastric Surgery the Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou 310022China Key Laboratory of Prevention Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang ProvinceHangzhou 310022China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Center of Gastrointestinal SurgeryPeking University Cancer Hospital&InstituteBeijing 100142China

Gastric cancer is one of the most common malignancies in China.According to the latest statistics in 2020,the incidence and mortality of gastric cancer all rank the third among all cancers,which have brought a huge burden to people’s health and social economy.Besides the high morbidity and mortality,the low early diagnosis rate is another dilemma of gastric cancer in China.Early gastric cancer accounts for only 20%of new gastric cancer cases in China.Most cases are already in the advanced stage when discovered,and the overall 5-year survival rate is less than50%(1,2).Over the past decades,China has made great progress in the prevention and treatment of gastric cancer,but it is still a relatively prominent health problem.

关键词： diagnosis prevention treatment

National guidelines for diagnosis and treatment of gastric cancer 2022 in China(English version)

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Chinese Journal of Cancer Research 2022年第3期34卷 207-237页

作者：无 jiafu ji Zhaode Bu jiahui Chen National Health Commission of the People's Republic of China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Peking University Cancer Hospital&Institute The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of Sciences

Contents 1.Overview 2.Diagnosis 2.1 Symptoms 2.2 Signs 2.3 Imaging 2.3.1 X-ray gas-barium double-contrast imaging 2.3.2 Ultrasonography(US)2.3.3 CT 2.3.4 MRI 2.3.5 Positron emission tomography(PET)-CT 2.3.6 Emission c... 详细信息

关键词： diagnosis gastric treatment

Characteristics of lymph node stations/basins metastasis and construction and validation of a preoperative combination prediction model that accurately excludes lymph node metastasis in early gastric cancer

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Chinese Journal of Cancer Research 2022年第5期34卷 519-532页

作者： Mengyu Feng jingtao Wei Ke ji Yinan Zhang Heli Yang Xiaojiang Wu ji Zhang Zhaode Bu jiafu ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Center of Gastrointestinal CancerPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:To explore the candidate indications for function-preserving curative gastrectomy and sentinel lymph node navigation surgery in early gastric cancer(EGC).Methods:The clinicopathological data of 561 patients with EGC who underwent radical gastrectomy for gastric cancer at Peking University Cancer Hospital from November 2010 to November 2020 with postoperative pathological stage pT1 and complete examination data,were collected.Pearson’s Chi-square test was used and binary logistic regression was employed for univariate and multivariate analyses.Combined analysis of multiple risk and protective factors for lymph node metastasis(LNM)of EGC was performed.A negative predictive value(NPV)combination model was built and validated.Results:LNM occurred in 85 of 561 patients with EGC,and the LNM rate was 15.15%.NPV for LNM reached 100%based on three characteristics,including ulcer-free,moderately well differentiation and patient2 cm was significantly greater than that noted in patients with a maximum tumor diameter≤2 cm(60.78%vs.28.13%,P<0.05).Conclusions:Characteristics of lymph node stations/basins metastasis will facilitate precise lymph node resection.The NPV for LNM reaches 100%based on the following two conditions:young and middle-aged EGC patients,well-differentiated tumors,and without ulcers;or well-differentiated tumors,without ulcers,and tumors located in the proximal stomach.These findings can be used as the recommended indications for functionpreserving curative gastrectomy and sentinel lymph node navigation surgery.

关键词： Early gastric cancer lymph node metastasis lymphatic basin negative predictive value function-preserving curative gastrectomy with lymphatic basin dissection

Double-tract reconstruction is superior to esophagogastrostomy in controlling reflux esophagitis and enhancing quality of life after proximal gastrectomy:Results from a prospective randomized controlled clinical trial in China

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Chinese Journal of Cancer Research 2023年第6期35卷 645-659页

作者： Yinan Zhang Hongtao Zhang Yan Yan Ke ji Ziyu jia Heli Yang Biao Fan Anqiang Wang Xiaojiang Wu ji Zhang jiafu ji Xin ji Zhaode Bu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Guowen(Changchun)International Hospital Changchun 136199China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchEndoscopy CenterPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:The aim of this study was to prospectively compare double-tract reconstruction(DTR)and esophagogastrostomy(EG)after proximal gastrectomy(PG)regarding the incidence of reflux esophagitis,quality of life(QOL),nutritional status and surgical safety.Methods:This study was a randomized controlled trial.Patients eligible for PG were enrolled and randomly assigned to the EG group and DTR group.The characteristics of patients,parameters for surgical safety,incidence of reflux esophagitis,nutrition status and QOL were collected and compared between the two groups.Univariate analysis and multivariate analysis were performed to determine the significant factors affecting the incidence of reflux esophagitis after PG.Results:Thirty-seven patients of the EG group and 36 patients of the DTR group were enrolled.The incidence of reflux esophagitis was significantly lower in the DTR group than in the EG group(8.3%vs.32.4%,P=0.019).The DTR group demonstrated a more favorable QOL than the EG group after PG.The nutritional status was balanced within the EG group and the DTR group.The operation time was longer in the DTR group than in the EG group(191 min vs.221 min,P=0.001),while surgical safety was similar in the two groups.Conclusions:Our research demonstrated that DTR is superior to EG after PG in terms of the incidence of reflux esophagitis and provides a more satisfactory QOL without increasing surgical complications or sacrificing nutritional status.

关键词： Double-tract reconstruction proximal gastrectomy quality of life reflux esophagitis

Correlation between imaging features on computed tomography and combined positive score of PD-L1 expression in patients with gastric cancer

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Chinese Journal of Cancer Research 2022年第5期34卷 510-518页

作者： Zhilong Wang Yinkui Wang Xiaoting Li Yanling Li Zhaode Bu Zhongwu Li Yingshi Sun jiafu ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of RadiologyBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Center of Gastrointestinal SurgeryBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of PathologyPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:To explore the correlation between computed tomography(CT)features and combined positive score(CPS)of programmed cell death ligand 1(PD-L1)expression in patients with gastric cancer(GC).Methods:This study reviewed an institutional database of patients who underwent GC operation without neoadjuvant chemotherapy between December 2019 and September 2020.The CPS results of PD-L1 expression of postoperative histological examination were recorded by pathology.Baseline CT features were measured,and their correlation with CPS 5 or 10 score groups of PD-L1 expression was analyzed.Results:Data for 153 patients with GC were collected.Among them,124 were advanced GC patients,and 29were early GC patients.None of the CT features significantly differed between CPS groups with a cutoff score of 5and a score of 10 in patients with early GC.In advanced GC,the presence of lymph nodes with short diameters>10mm was significantly different(P=0.024)between the CPS10 mm significantly differed between the CPS<10 and CPS≥10 groups in advanced GC.The sensitivity,specificity and area under receiver operating characteristic(ROC)curve of logistic regression model for predicting CPS≥10 was 71.7%,50.0%and 0.671,respectively.Microsatellite instability(MSI)status was significantly different in CPS groups with cutoff score of 5 and 10 in advanced GC patients.Conclusions:CT findings of advanced GC patients with CPS≥10 showed greater arterial phase enhancement and larger lymph nodes.CT has the potential to help screen patients suitable for immunotherapy.

关键词： Gastric cancer computed tomography combined positive score

Exploration and optimization of surgical techniques for laparoscopic transhiatal lower mediastinal lymph node dissection for adenocarcinoma of esophagogastric junction: A prospective IDEAL 2a study with qualitative design

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Chinese Journal of Cancer Research 2023年第2期35卷 163-175页

作者： Yinkui Wang Fanling Hong Shuangxi Li Fei Shan Yongning jia Rulin Miao Zhemin Li Ziyu Li jiafu ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Endoscopy Center Zhongshan HospitalFudan University(Xiamen Branch)Xiamen 361015China

Objective: To explore the change and feasibility of surgical techniques of laparoscopic transhiatal(TH)-lower mediastinal lymph node dissection(LMLND) for adenocarcinoma of the esophagogastric junction(AEG)according to Idea, Development, Exploration, Assessment, and Long-term follow-up(IDEAL) 2a standards.Methods: Patients diagnosed with AEG who underwent laparoscopic TH-LMLND were prospectively included from April 14, 2020, to March 26, 2021. Clinical and pathological information as well as surgical outcomes were quantitatively analyzed. Semistructured interviews with the surgeon after each operation were qualitatively analyzed.Results: Thirty-five patients were included. There were no cases of transition to open surgery, but three cases involved combination with transthoracic surgery. In qualitative analysis, 108 items under three main themes were detected: explosion, dissection, and reconstruction. Revised instruction was subsequently designed according to the change in surgical technique and the cognitive process behind it. Three patients had anastomotic leaks postoperatively, with one classified as Clavien-Dindo Ⅲa.Conclusions: The surgical technique of laparoscopic TH-LMLND is stable and feasible;further IDEAL 2b research is warranted.

关键词： Adenocarcinoma of esophagogastric junction laparoscopic surgery transhiatal approach lower mediastinal lymph node dissection IDEAL 2a research