Dual primary gastric and colorectal cancer:The known hereditary causes and underlying mechanisms

In this editorial,I commented on the paper by Lin et al,published in this issue of the World Journal of Gastrointestinal Oncology.The work aimed at analysing the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with dual primary gastric and colorectal cancer(CRC).The authors concluded the necessity for regular surveillance for metachronous cancer during postoperative follow-up and reported the prognosis is influenced by the gastric cancer(GC)stage rather than the CRC stage.Although surveillance was recommended in the conclusion,the authors did not explore this area in their study and did not include tests used for such surveillance.This editorial focuses on the most characterized gastrointestinal cancer susceptibility syndromes concerning dual gastric and CRCs.These include hereditary diffuse GC,familial adenomatous polyposis,hereditary nonpolyposis colon cancer,Lynch syndrome,and three major hamartomatous polyposis syndromes associated with CRC and GC,namely Peutz-Jeghers syndrome,juvenile polyposis syndrome,and PTEN hamartoma syndrome.Careful assessment of these syndromes/conditions,including inheritance,risk of gastric and colorectal or other cancer development,genetic mutations and recommended genetic investigations,is crucial for optimum management of these patients.

Mutational separation and clinical outcomes of TP53 and CDH1 in gastric cancer

BACKGROUND Gastric cancer(GC)is a deadly tumor with the fifth highest occurrence and highest global mortality rates.Owing to its heterogeneity,the underlying mechanism of GC remains unclear,and chemotherapy offers little benefit to individuals.AIM To investigate the clinical outcomes of TP53 and CDH1 mutations in GC.METHODS In this study,202 gastric adenocarcinoma tumor tissues and their corresponding normal tissues were collected.A total of 490 genes were identified using target capture.Through t-test and Wilcoxon rank-sum test,somatic mutations,microsatellite instability,and clinical statistics,including overall survival,were detected,compared,and calculated.RESULTS The mutation rates of 32 genes,including TP53,SPEN,FAT1,and CDH1 exceeded 10%.TP53 mutations had a slightly lower overall occurrence rate(33%).The TP53 mutation rate was significantly higher in advanced stages(stage Ⅲ/Ⅳ)than that in early stages(stage Ⅰ/Ⅱ)(P<0.05).In contrast,CDH1 mutations were significantly associated with diffuse GC.TP53 is related to poor prognosis of advanced-stage tumors;nevertheless,CDH1 corresponds to a diffuse type of cancer.TP53 is exclusively mutated in CDH1 and is primarily affected by two distinct GC mechanisms.CONCLUSION Different somatic mutation patterns in TP53 and CDH1 indicate two major mechanisms of GC.

Hereditary diffuse gastric cancer: What the clinician should know

Hereditary diffuse gastric cancer(HDGC) is an inherited autosomal dominant syndrome with a penetrance of up to 80% affecting diverse geographic populations. While it has been shown to be caused mainly by germline alterations in the E-cadherin gene(CDH1), problematically, the genetic diagnosis remains unknown in up to 60% of patients. Given the important knowledge gaps regarding the syndrome, asymptomatic carriers of CDH1 mutations are advised for a prophylactic total gastrectomy. Intensive annual endoscopic surveillance is the alternative for carriers who decline gastrectomy. As HDGCs have a prolonged indolent phase, this provides a window of opportunity for surveillance and treatment. Recent findings of other gene defects in CTNNA1 and MAP3K6, as well as further characterization of CDH1 mutations and their pathogenicity will change the way HDGC patients are counselled for screening, surveillance and treatment. This review will bring the reader up to date with these changes and discuss future directions for research; namely more accurate risk stratification and surveillance methods to improve clinical care of HDGC patients.

Frequent loss of heterozygosity at 8p22 chromosomal region in diffuse type of gastric cancer

AIM: To study the loss of heterozygosity (LOH) at 8p21-23 locus in diffuse gastric cancer.METHODS: To evaluate the involvement of this region in gastric cancer, we used eight microsatellite markers covering two Mb of mentioned region, to perform a high-resolution analysis of allele loss in 42 cases of late diffuse gastric adenocarcinoma.RESULTS: Six of these STS makers: D8S1149, D8S1645, D8S1643, D8S1508, D8S1591, and D8S1145 showed 36%, 28%, 37%, 41%, 44% and 53% LOH, respectively.CONCLUSION: A critical region of loss, close to the NAT2 locus and relatively far from FEZ1 gene currently postulated as tumor suppressor gene in this region.

The role of endoscopy in the management of hereditary diffuse gastric cancer syndrome

Hereditary diffuse gastric cancer(HDGC) syndrome is an inherited cancer risk syndrome associated with path-ogenic germline CDH1 variants. Given the high risk for developing diffuse gastric cancer, CDH1 carriers are recommended to undergo prophylactic total gastrectomy for cancer risk reduction. Current guidelines recommend upper endoscopy in CDH1 carriers prior to surgery and then annually for individuals deferring prophylactic total gastrectomy.Management of individuals from HDGC families without CDH1 pathogenic variants remains less clear, and management of families with CDH1 pathogenic variants in the absence of a family history of gastric cancer is particularly problematic at present. Despite adherence to surveillance protocols, endoscopic detection of cancer foci in HDGC is suboptimal and imperfect for facilitating decision-making. Alternative endoscopic modalities, such as chromoendoscopy,endoscopic ultrasound, and other non-white light methods have been utilized,but are of limited utility to further improve cancer detection and risk stratification in HDGC. Herein, we review what is known and what remains unclear about endoscopic surveillance for HDGC, among individuals with and without germline CDH1 pathogenic variants. Ultimately, the use of endoscopy in the management of HDGC remains a challenging arena, but one in which further research to improve surveillance is crucial.

Germline mutations in hereditary diffuse gastric cancer

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Among which, about 1%–3% of gastric cancer patients were characterized by inherited gastric cancer predisposition syndromes, knowing as hereditary diffuse gastric cancer（HDGC）. Studies reported that CDH1 germline mutations are the main cause of HDGC. With the help of rapid development of genetic testing technologies and data analysis tools, more and more researchers focus on seeking candidate susceptibility genes for hereditary cancer syndromes. In addition, National Comprehensive Cancer Network（NCCN） guidelines recommend that the patients of HDGC carrying CDH1 mutations should undergo prophylactic gastrectomy or routine endoscopic surveillances. Therefore, genetic counseling plays a key role in helping individuals with pathogenic mutations make appropriate risk management plans. Moreover, experienced and professional genetic counselors as well as a systematic multidisciplinary team（MDT） are also required to facilitate the development of genetic counseling and benefit pathogenic mutation carriers who are in need of regular and standardized risk management solutions. In this review, we provided an overview about the germline mutations of several genes identified in HDGC, suggesting that these genes may potentially act as susceptibility genes for this malignant cancer syndrome. Furthermore, we introduced information for prevention, diagnosis and risk management of HDGC. Investigations on key factors that may have effect on risk management decision-making and genetic data collection of more cancer syndrome family pedigrees are required for the development of HDGC therapeutic strategies.

Hereditary diffuse gastric cancer: One family's story

Hereditary diffuse gastric cancer(HDGC) is an inherited form of gastric cancer that carries a poor prognosis. Most HDGCs are caused by an autosomal dominant genetic mutation in the CDH1 gene, which carries a 70%-80% lifetime risk of gastric cancer. Given its submucosal origin, endoscopic surveillance is an unreliable means of early detection, and prophylactic gastrectomy is recommended for CDH1 positive individuals older than age 20 years. We describe the case of a male with recurrent gastric cancer who was diagnosed with HDGC secondary to the CDH1 mutation, and we also describe the patient's pedigree and outcomes of recommended genetic testing.

Molecular Pathology of Hereditary Diffuse Gastric Cancer

Hereditary diffuse gastric cancer is a rare, autosomal dominant hereditary cancer syndrome associated with germline mutations in CDH1 in which 60% - 80% of affected individuals develop advanced diffuse gastric cancer, many as young adults. At clinical presentation, ~90% of these malignancies represent advanced, surgically incurable disease. As such, presymptomatic identification of germline CDH1 mutation carriers followed by early prophylactic total gastrictomy is the sole effective management strategy available. DNA sequence analysis of the CDH1 gene to identify the affected germline allele is the diagnostic standard of care;however, CDH1’s relatively high frequency of polymorphisms and the limited amount of experience available regarding them dictate that many identified variants are, as yet, of unknown clinical significance. Given the dramatic consequences of inappropriately offered or withheld treatment, careful clinical selection of at-risk individuals is critical. To facilitate this, multiple groups have published screening criteria recommendations, and while there is disagreement regarding the optimal diagnostic approach, the most widely-used overlap to a considerable degree.

Case series of three patients with hereditary diffuse gastric cancer in a single family:Three case reports and review of literature

BACKGROUND Hereditary diffuse gastric cancer(HDGC)is a familial cancer syndrome often associated with germline mutations in the CDH1 gene.However,the frequency of CDH1 mutations is low in patients with HDGC in East Asian countries.Herein,we report three cases of HDGC harboring a missense CDH1 variant,c.1679C>G,from a single Japanese family.CASE SUMMARY A 26-year-old female(Case 1)and a 51-year-old male(father of Case 1),who had a strong family history of gastric cancer,were diagnosed with advanced diffuse gastric cancer.After genetic counselling,a 25-year-old younger brother of Case 1 underwent surveillance esophagogastroduodenoscopy that detected small signet ring cell carcinoma foci as multiple pale lesions in the gastric mucosa.Genetic analysis revealed a CDH1 c.1679C>G variant in all three patients.CONCLUSION It is important for individuals suspected of having HDGC to be actively offered genetics evaluation.This report will contribute to an increased awareness of HDGC.

Endoscopic Kyoto classification of Helicobacter pylori infection and gastric cancer risk diagnosis

Recent advances in endoscopic technology allow detailed observation of the gastric mucosa.Today,endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori(H.pylori)infection and evaluate gastric cancer risk.In 2013,the Japan Gastroenterological Endoscopy Society advocated the Kyoto classification,a new grading system for endoscopic gastritis.The Kyoto classification organized endoscopic findings related to H.pylori infection.The Kyoto classification score is the sum of scores for five endoscopic findings(atrophy,intestinal metaplasia,enlarged folds,nodularity,and diffuse redness with or without regular arrangement of collecting venules)and ranges from 0 to 8.Atrophy,intestinal metaplasia,enlarged folds,and nodularity contribute to gastric cancer risk.Diffuse redness and regular arrangement of collecting venules are related to H.pylori infection status.In subjects without a history of H.pylori eradication,the infection rates in those with Kyoto scores of 0,1,and≥2 were 1.5%,45%,and 82%,respectively.A Kyoto classification score of 0 indicates no H.pylori infection.A Kyoto classification score of 2 or more indicates H.pylori infection.Kyoto classification scores of patients with and without gastric cancer were 4.8 and 3.8,respectively.A Kyoto classification score of 4 or more might indicate gastric cancer risk.

Apparent diffusion coefficient by diffusion-weighted magnetic resonance imaging as a sole biomarker for staging and prognosis of gastric cancer

Objective： To investigate the role of apparent diffusion coefficient （ADC） from diffusion-weighted magnetic resonance imaging （DW-MRI） when applied to the 7th TNM classification in the staging and prognosis of gastric cancer （GC）. Methods： Between October 2009 and May 2014, a total of 89 patients with non-metastatic, biopsy proven GC underwent 1.5T DW-MRI, and then treated with radical surgery. Tumor ADC was measured retrospectively and compared with final histology following the 7th TNM staging （local invasion, nodal involvement and according to the different groups -- stage Ⅰ, Ⅱ and Ⅲ）. Kaplan-Meier curves were also generated. The follow-up period is updated to May 2016. Results： Median follow-up period was 33 months and 45/89 （51%） deaths from GC were observed. ADC was significantly different both for local invasion and nodal involvement （P〈0.001）. Considering final histology as the reference standard, a preoperative ADC cut-offof 1.80×10-3 mm^2/s could distinguish between stages I and Ⅱ and an ADC value of ≤1.36-10-3 mm^2/s was associated with stage Ⅲ（P〈0.001）. Kaplan-Meier curves demonstrated that the survival rates for the three prognostic groups were significantly different according to final histology and ADC cut-offs （P〈0.001）. Conclusions： ADC is different according to local invasion, nodal involvement and the 7th TNM stage groups for GC, representing a potential, additional prognostic biomarker. The addition of DW-MRI could aid in the staging and risk stratification of GC.

Gastroesophageal signet ring cell carcinoma morbidity and mortality: A retrospective review

BACKGROUND Upper gastrointestinal(GI)signet ring cell carcinomas(SRCC)confer a poor prognosis.The benefit of operative intervention for this patient group is contro-versial in terms of overall survival.AIM To investigate factors relating to survival in patients with upper GI SRCC.METHODS A retrospective,tertiary,single-centre review of patients who were diagnosed with oesophageal,gastroesophageal junction and gastric SRCC was performed.The primary outcome was to compare mortality of patients who underwent operative management with those who had nonoperative management.Secon-dary outcomes included assessing the relationship between demographic and histopathological factors,and survival.RESULTS One hundred and thirty-one patients were included.The one-year survival for the operative group was 81%and for the nonoperative group was 19.1%.The five-year survival in the operative group was 28.6%vs 1.5%in the nonoperative group.The difference in overall survival between groups was statistically significant(HR 0.19,95%CI(0.13-0.30),P<0.001).There was no difference in survival when ad-justing for age,smoking status or gender.On multivariate analysis,patients who underwent surgical management,those with a lower stage of disease,and those with a lower Charlson Comorbidity Index(CCI)had significantly improved sur-vival.CONCLUSION Well-selected patients with upper GI SRCC appear to have reasonable medium-term survival following surgery.Offering surgery to a carefully selected patient group may improve the outcome for this disease.

MRI弥散加权成像与表观弥散系数对胃癌T分期的诊断价值

目的探讨MRI弥散加权成像(DWI)和表观弥散系数(ADC)对胃癌T分期的诊断价值。方法86例胃癌患者均进行MRI检查,以病理检查结果作为诊断金标准,分析DWI和ADC值对胃癌T分期的诊断价值。结果ADC值诊断胃癌T分期的准确度为80.23%(69/86),Kappa值=0.704;DWI诊断胃癌T分期的准确度为81.40%(70/86),Kappa值为0.727;ADC值联合DWI诊断胃癌T分期的准确度为91.86%(79/86),高于ADC值和DWI单独检查,Kappa值为0.878。T_(1~2)期胃癌患者的ADC值为(1.17±0.23)×10^(-3) mm^(2)/s,明显高于T_(3~4)期患者的(0.83±0.14)×10^(-3) mm^(2)/s,差异有统计学意义(P﹤0.01)。ADC值、DWI信号强度、f值联合检查对胃癌T分期的诊断价值优于三者单独检查。结论ADC值联合DWI可为胃癌T分期的诊断提供一定临床依据,但ADC值因受多种因素影响,对胃癌T分期之间的区分具有一定局限性。

MutL蛋白同系物1/MutS蛋白同系物2表达缺失与弥漫浸润型胃癌临床病理特征及预后关系

目的探讨MutL蛋白同系物1(MLH1)/MutS蛋白同系物2(MSH2)表达缺失与弥漫浸润型胃癌临床病理特征及预后关系。方法回顾性分析2020年3月至2022年7月皖南医学院第二附属医院收治的157例弥漫浸润型胃癌患者的临床资料,分析MLH1/MSH2表达缺失与弥漫浸润型胃癌临床病理特征的关系,随访1年,记录患者生存情况,分析弥漫浸润型胃癌患者预后的影响因素。结果157例患者中,MLH1/MSH2表达缺失16例,缺失率为10.19%。低分化、Ⅲ期、淋巴结转移的患者MLH1/MSH2表达缺失率高于中高分化、Ⅰ~Ⅱ期、淋巴结未转移患者,差异有统计学意义(P<0.05)。随访1年,MLH1/MSH2表达未缺失患者生存曲线优于MLH1/MSH2表达缺失患者,差异有统计学意义(P<0.05)。TNM分期、术后并发症、MLH1/MSH2表达缺失为弥漫浸润型胃癌患者预后的危险因素(P<0.05)。结论MLH1/MSH2表达缺失与弥漫浸润型胃癌患者肿瘤分化程度、TNM分期、淋巴结转移及预后密切相关,且MLH1/MSH2表达缺失者预后更差。

Molecular genetics of gastric adenocarcinoma in clinical practice

The molecular genetics of gastric carcinoma(GC) dictates their biology and clinical behavior. The two morphologically distinct types of gastric carcinoma by Lauren classification, i.e., intestinal and diffuse cell types, have a significant difference in clinical outcome. These two types of GC have different molecular pathogenetic pathways with unique genetic alterations. In addition to environmental and other etiologies, intestinal type GC is associated with Helicobacter pylori(H. pylori) infection and involves a multistep molecular pathway driving the normal epithelium to intestinal metaplasia, dysplasia, and malignant transformation by chromosomal and/or microsatellite instability(MSI), mutation of tumor suppressor genes, and loss of heterozygosity among others. Diffuse type shows no clear causal relationship with H. pylori infection, but is commonly associated with deficiency of cell-cell adhesion due to mutation of the E-cadherin gene(CDH1), and a manifestation of the hereditary gastric cancer syndrome. Thus, detection of CDH1 mutation or loss of expression of E-cadherin may aid in early diagnosis or screening of diffuse type GC. Detection of certain genetic markers, for example, MSI and matrix metalloproteinases, mayprovide prognostic information, particularly for intestinal type. The common genetic alterations may offer therapeutic targets for treatment of GC. Polymorphisms in Thymidylate synthase to metabolize 5-fluorouracil, glutathione S-transferase for degradation of Cisplatin, and amplification/overexpression of human epidermal growth factor receptor 2 targeted by monoclonal antibody Trastuzumab, are a few examples. P13K/Akt/mT OR pathway, c-Met pathways, epidermal growth factor receptor, insulin-like growth factor receptor, vascular endothelial growth factor receptor fibroblast growth factor receptor, and micro RNAs are several potential therapeutic biomarkers for GC under investigation.

基于SEER数据库的弥漫型胃癌患者预后列线图模型构建及验证

目的:筛选弥漫型胃癌患者预后因素并构建预后列线图,并验证其预测准确性。方法 :从SEER数据库收集2006—2018年病理诊断为弥漫型胃癌的2877例患者的临床病理特征,随机将患者分为训练队列(1439例)和验证队列(1438例)。利用单因素Log-rank及多因素COX分析筛选出独立预后因素并构建预后列线图,预测1、3、5年的总生存期(OS),使用一致性指数和校准曲线确定列线图预测的准确性和判别能力。结果:年龄、T、N、M、TNM、手术状态、化疗状态7个指标均是OS的独立预后因素(P<0.05),基于独立预后因素构建了1、3、5年OS的列线图。训练队列中列线图的c-指数为0.750(95%CI:0.734~0.766),高于TNM分期系统0.658(95%CI:0.639~0.677);验证队列列线图的c-指数为0.753(95%CI:0.737~0.769),高于TNM分期系统0.679(95%CI:0.503~0.697)。校准曲线表明了列线图预测生存率与实际生存率具有良好的一致性。结论:预后列线图能够准确预测弥漫性胃癌患者预后,有助于临床医师对弥漫型胃癌患者进行个体化的预后评估及治疗方案的制定。

MRI联合DWI对胃间质瘤与胃癌的鉴别价值分析

目的分析磁共振成像(MRI)联合扩散加权成像(DWI)对胃间质瘤与胃癌的鉴别价值。方法回顾性分析经手术病理证实并行MRI联合DWI检查的65例胃癌患者及21例间质瘤患者的影像资料。对比分析胃间质瘤和胃癌在MRI联合DWI检查中的影像学表现及ADC值,绘制ROC曲线分析ADC值鉴别诊断胃间质瘤与胃癌的价值,采用Kappa检验评价MRI联合DWI检查中的ADC值诊断结果与手术病理检查结果的一致性。结果86例研究对象中T_(2)WI压脂、DWI图像上均呈不同程度的高信号,虽然胃癌的图像信号强度总体上略高于胃间质瘤,但二者征象特征并不易准确区分;此外,可见胃间质瘤多发于胃体、胃底,胃癌多发于胃窦。胃癌患者ADC值为(1.05×10^(-3)±0.27×10^(-3))s/mm^(2),显著低于胃间质瘤患者ADC值[(1.43×10^(-3)±0.21×10^(-3))s/mm^(2)](t=5.891,P<0.05)。ADC值鉴别诊断胃间质瘤与胃癌的曲线下面积为0.865,约登指数为0.688,临界值为1.26×10^(-3)s/mm^(2),此时对应的敏感度为83.08%,特异性为85.71%,准确度为83.72%,误诊率为14.29%,漏诊率为16.92%,阳性预测值为94.74%,阴性预测值为62.07%。MRI联合DWI检查中的ADC值诊断结果与手术病理检查结果比较,Kappa值为0.609(P<0.05),说明一致性较高。结论MRI联合DWI检查作为一种无创的影像学检查技术,有助于鉴别诊断胃间质瘤与胃癌,具有一定的临床应用价值。

磁共振参数结合临床数据构建胃癌伴淋巴结转移的预测模型

目的基于磁共振参数和临床数据构建胃癌患者淋巴结转移的风险预测模型并进行验证。方法回顾性总结2018年6月至2022年6月病理确诊胃癌患者160例为研究对象,术前检测外周血癌胚抗原(CEA)和CA199,采用3.0T MRI获得T1-横轴位、T2-冠状位和横轴位以及扩散加权成像(DWI),判断肿瘤T和N分期,测量表观扩散系数(ADC)_(mean)。根据病理结果证实有无淋巴结转移。结果160例患者中52例病理证实淋巴结转移,发生率为32.5%(52/160)。单因素比较发现,淋巴结转移阳性组患者血清CEA和CA199明显高于阴性组,ADC_(mean)降低,T分期(T3~T4)、N(阳性)、切缘阳性、壁外血管侵犯和低分化增多(P<0.05)。多因素Logistic回归分析显示,CA199和ADC_(mean)、T分期、N(阳性)和分化级别是淋巴结转移的独立预测因素(P<0.05)。构建预测模型Y=0.562+0.123×(CA199)-0.285×(ADC_(mean))+0.896×(T分期)+1.256×N+0.758×(分化级别)。受试者工作曲线(ROC)显示,预测模型诊断淋巴结转移的曲线下面积(AUC)为0.895(P<0.05)。结论术前胃癌磁共振检查有助于判断淋巴结转移,血清CA199升高、ADC_(mean)降低、T分期升高、N阳性和低分化是淋巴结转移的独立预测因素,建立预测模型有较高的诊断潜力,便于临床推广应用。

3.0T磁共振在胃癌术前TN分期中的诊断价值

目的探讨3.0T磁共振成像(MRI)在胃癌术前T、N分期中的诊断价值。方法将2018年6月-2019年12月接受手术治疗的64例胃癌患者纳入本次研究,依据AJCC胃癌TNM分期标准,对入组患者进行影像学T、N分期,并将术前影像分期与术后病理结果进行比较。结果入组的64例患者均接受根治性手术,术后经病理组织学验证发现:MRI评估胃癌T分期总准确度为82.81%,其中T1分期的准确度为66.67%,T2分期的准确度为78.95%,T3分期的准确度为88.0%,T4分期的准确度为85.7%,与病理诊断一致性较好(κ=0.784);磁共振扩散加权成像(DWI)序列扫描,胃周转移淋巴结ADCmin值[(1.012±0.068)×10^(-3)mm^(2)/s比(1.427±0.139)×10^(-3)mm^(2)/s]显著低于非转移淋巴结;DWI序列ADCmin值评估胃癌N分期总准确度为81.25%,其中N0分期准确度为83.33%,N1分期准确度为75.0%,N2分期准确度为71.43%,N3分期准确度为85.71%,与病理诊断一致性较好(κ=0.722)。ADCmin值评估胃周淋巴结转移的ROC曲线下面积为0.796,ADCmin值取最佳阈值1.129×10^(-3)mm^(2)/s时,其敏感度为86.8%,特异度为77.4%。结论3.0T磁共振成像对胃癌患者术前T、N分期的诊断准确率较高,与病理诊断的一致性好,值得临床推广。

弥漫型胃癌的治疗探索

弥漫型胃癌(diffuse gastric cancer,DGC)是一种分化程度低、恶性程度高、临床预后差的胃腺癌亚型,异质性强,可由CDH1基因突变、RHOA基因突变和CLDN18-ARHGAP基因融合等驱动,也存在广泛的环境-基因突变互作,发病机制尚不清楚。已有的DGC研究模型包括基因修饰小鼠、人源肿瘤异种移植(patient-derived tumor xenograft,PDX)模型以及类器官模型,有机整合这些研究模型有助于更加准确地探索DCG病理生理过程,揭示DGC发生机制。临床上尚缺乏高效的DGC治疗药物,近年来开发了MET抑制剂、ROS1抑制剂等多种分子靶向药物,但未获得显著的临床疗效。鉴于此,本文展望宏基因组学、蛋白组学、代谢组学等新兴领域,综合DGC时空异质性、胃癌微生态调控和多组学整合的分子分型等前沿成果,提出DGC精准治疗的未来着力点和攻关方向,以期为DGC精准诊疗提供理论参考。