Gastric cancer is one of the most common malignant tumors in the world. The incidence and mortality of gastric cancer rank high not only in China, but also in the world. In recent years, with the deepening of research on gastric cancer, it has been gradually found that gastric cancer in different locations (gastric antrum, gastric body, gastric fundus and cardia, etc.) is different in pathogenesis, clinicopathological characteristics, molecular biological characteristics, and prognosis of patients. This article reviews the differences in epidemiology, pathological and clinical characteristics, pathogenesis and the research progress of diagnosis and treatment of gastric cancer at different sites, so as to provide ideas and theoretical basis for the precise treatment of gastric cancer in China.
References
[1]
Siegel, R.L., Kratzer, T.B., Giaquinto, A.N., Sung, H. and Jemal, A. (2025) Cancer Statistics, 2025. CA: A Cancer Journal for Clinicians, 75, 10-45. https://doi.org/10.3322/caac.21871
[2]
Medical Administration of National Health Commission of the People’s Republic of China (2010) Guidelines for Diagnosis and Treatment of Gastric Cancer. Chinese Journal of Digestive Surgery, 34, 71-79.
[3]
GBD 2021 Diseases and Injuries Collaborators (2024) Global Incidence, Prevalence, Years Lived with Disability (YLDs), Disability-Adjusted Life-Years (DALYs), and Healthy Life Expectancy (HALE) for 371 Diseases and Injuries in 204 Countries and Territories and 811 Subnational Locations, 1990-2021: A Systematic Analysis for the Global Burden of Disease Study 2021. The Lancet, 403, 2133-2161.
[4]
Cao, S. (2021) Comparative Analysis of Clinicopathological Characteristics and Prognosis of Gastric Cancer at Different Locations. Chinese Medicine Guidelines, 12, 58-60.
[5]
Wang, L., Xin, X.M., Yan X.Y., et al. (2021) Expression of Placenta-Specific Gene 1 in Different Parts of Gastric Cancer and Its Relationship with Clinicopathological Features and Prognosis. Chinese Journal of Cancer, 37, 712-715.
[6]
Gu, Y., Chen, G., Zhang, Y., et al. (2019) Relationship between Location, Age of Onset and Clinicopathological Features in Patients with Gastric Cancer. Modern Biomedical Progress, 12, 3119-3123.
[7]
Sheikh, A.F., Yadyad, M.J., Goodarzi, H., Hashemi, S.J., Aslani, S., Assarzadegan, M., etal. (2018) CagA and vacA Allelic Combination of Helicobacter pylori in Gastroduodenal Disorders. MicrobialPathogenesis, 122, 144-150. https://doi.org/10.1016/j.micpath.2018.06.023
[8]
Drake, I., Dias, J.A., Teleka, S., Stocks, T. and Orho‐Melander, M. (2019) Lifestyle and Cancer Incidence and Mortality Risk Depending on Family History of Cancer in Two Prospective Cohorts. InternationalJournalofCancer, 146, 1198-1207. https://doi.org/10.1002/ijc.32397
van der Sluis, L., van Dieren, J.M., van der Post, R.S. and Bisseling, T.M. (2024) Current Advances and Challenges in Managing Hereditary Diffuse Gastric Cancer (HDGC): A Narrative Review. HereditaryCancerinClinicalPractice, 22, Article No. 21. https://doi.org/10.1186/s13053-024-00293-5
[11]
Ning, F.-L., Zhang, N.-N., Wang, J., Jin, Y.-F., Quan, H.-G., Pei, J.-P., etal. (2021) Prognostic Value of Modified Lauren Classification in Gastric Cancer. WorldJournalofGastrointestinalOncology, 13, 1184-1195. https://doi.org/10.4251/wjgo.v13.i9.1184
[12]
Smyth, E.C., Nilsson, M., Grabsch, H.I., van Grieken, N.C.T. and Lordick, F. (2020) Gastric Cancer. TheLancet, 396, 635-648. https://doi.org/10.1016/s0140-6736(20)31288-5
[13]
Xiu, J., Ma, L., Ding, Y., et al. (2022) The Diagnosis of Early Gastric Cancer Based on Medical Imaging Technology and Mathematical Modeling. Computational and Mathematical Methods in Medicine, 2022, Article 8721654. https://doi.org/10.1155/2022/8721654
[14]
Hong, L.L., Zhang, Y. and Liu, Z.Y. (2018) Neuroendocrine Carcinoma of Esophageal and Gastric Cardia: Clinicopathologic and Immunohistochemistry Study of 80 Cases. Oncotarget, 9, 10754-10764. https://doi.org/10.18632/oncotarget.23610
[15]
Lu, J.H., Wang, Q., Zhang, H.Z., Liu, J.W., Ren, J.N., Fan, J., etal. (2024) Analysis of Endoscopic and Pathological Features of 6961 Cases of Gastric Cancer. ScientificReports, 14, Article No. 7159. https://doi.org/10.1038/s41598-024-58018-6
[16]
Osman, A.G.A. (2019) Molecular Detection of Helicobacter pylori GLmM Gene among Gastritis and Duodenitis Patients in Albogaa Specialized Hospital-Omdurman. Sudan University of Science and Technology.
[17]
Matsunaga, S., Nishiumi, S., Tagawa, R. and Yoshida, M. (2018) Alterations in Metabolic Pathways in Gastric Epithelial Cells Infected with Helicobacter pylori. MicrobialPathogenesis, 124, 122-129. https://doi.org/10.1016/j.micpath.2018.08.033
[18]
Shelekhova, Y.V., Hramtsova, N.A., Onuchina, E.V. and Kuklin, S.G. (2015) Study of the Variability of the Cardiac Rhythm in Railroad Employees, Who Suffer by Stomach Ulcer and Duodenum, Associated and Nonassociated with the Infection Helicobacter pylori. Eksp Klin Gastroenterol, No. 6, 36-40.
[19]
Hu, B., Khara, P., Song, L., Lin, A.S., Frick-Cheng, A.E., Harvey, M.L., etal. (2019) In Situ Molecular Architecture of the Helicobacter pylori Cag Type IV Secretion System. mBio, 10, e00849-19. https://doi.org/10.1128/mbio.00849-19
[20]
Alfarouk, K.O., Bashir, A.H.H., Aljarbou, A.N., Ramadan, A.M., Muddathir, A.K., AlHoufie, S.T.S., etal. (2019) The Possible Role of Helicobacter pylori in Gastric Cancer and Its Management. FrontiersinOncology, 9, Article 75. https://doi.org/10.3389/fonc.2019.00075
[21]
Maleki Kakelar, H., Barzegari, A., Dehghani, J., Hanifian, S., Saeedi, N., Barar, J., etal. (2018) Pathogenicity of Helicobacter pylori in Cancer Development and Impacts of Vaccination. GastricCancer, 22, 23-36. https://doi.org/10.1007/s10120-018-0867-1
[22]
Hatakeyama, M. (2014) Helicobacter pylori CagA and Gastric Cancer: A Paradigm for Hit-and-Run Carcinogenesis. CellHost&Microbe, 15, 306-316. https://doi.org/10.1016/j.chom.2014.02.008
[23]
Chen, L., Liu, Y.C., Zheng, Y.Y., et al. (2019) Furanodienone Overcomes Temozolomide Resistance in Glioblastoma through the Downregulation of CSPG4-Akt-ERK Signalling by Inhibiting EGR1-Dependent Transcription. Phytotherapy Research, 33, 1736-1747. https://doi.org/10.1002/ptr.6363
[24]
Icard, P., Fournel, L., Wu, Z., et al. (2019) Interconnection between Metabolism and Cell Cycle in Cancer. Trends in Biochemical Sciences, 44, 490-501. https://doi.org/10.1016/j.tibs.2018.12.007
[25]
Zhang, X., Zhang, P. and Aboul-Soud, M.A.M. (2016) From Inflammation to Gastric Cancer: Role of Helicobacter pylori. Oncology Letters, 13, 543-548. https://doi.org/10.3892/ol.2016.5506
[26]
Olea, G.B., Aguirre, M.V. and Lombardo, D.M. (2019) Differential Expression of E-and N-Cadherins during Gonadal Histogenesis in Columba Livia (Aves: Columbiformes). ActaHistochemica, 121, 354-360. https://doi.org/10.1016/j.acthis.2019.02.006
[27]
Li, M., Chen, T., Wang, R., Luo, J.-Y., He, J., Ye, R.-S., etal. (2019) Plant MIR156 Regulates Intestinal Growth in Mammals by Targeting the Wnt/β-Catenin Pathway. AmericanJournalofPhysiology-CellPhysiology, 317, C434-C448. https://doi.org/10.1152/ajpcell.00030.2019
[28]
Song, Y.B., Zhou, D.M., Zhang, P., Zhu, N., Guo, R.J., Wang, T., etal. (2024) Heparanase Accelerates the Angiogenesis and Inhibits the Ferroptosis of P53-Mutant Non-Small Cell Cancers in VEGF-Dependent Manner. Cytotechnology, 76, 503-517. https://doi.org/10.1007/s10616-024-00632-3
[29]
Sato, T., Saito, M., Nakajima, S., Saito, K., Katagata, M., Fukai, S., et al. (2023) ARID1A Deficiency Is Targetable by AKT Inhibitors in HER2-Negative Gastric Cancer. GastricCancer, 26, 379-392. https://doi.org/10.1007/s10120-023-01373-6
[30]
Zhang, J., Yuan, C.L. and Ma, X. (2025) Efficacy and Safety of Different Drugs in Patients with HER2-Positive Gastric Cancer: Network Meta-Analysis. SystematicReviews, 14, Article No. 40. https://doi.org/10.1186/s13643-025-02777-4
[31]
Fukayama, M., Abe, H., Kunita, A., Shinozaki-Ushiku, A., Matsusaka, K., Ushiku, T., etal. (2019) Thirty Years of Epstein-Barr Virus-Associated Gastric Carcinoma. VirchowsArchiv, 476, 353-365. https://doi.org/10.1007/s00428-019-02724-4
[32]
The Cancer Genome Atlas Research Network (2014) Comprehensive Molecular Characterization of Gastric Adenocarcinoma Molecular Characterization of Gastric Adenocarcinoma. Nature, 513, 202-209.
[33]
Matsusaka, K., Kaneda, A., Nagae, G., Ushiku, T., Kikuchi, Y., Hino, R., etal. (2011) Classification of Epstein-Barr Virus-positive Gastric Cancers by Definition of DNA Methylation Epigenotypes. CancerResearch, 71, 7187-7197. https://doi.org/10.1158/0008-5472.can-11-1349
[34]
Saito, R., Abe, H., Kunita, A., Yamashita, H., Seto, Y. and Fukayama, M. (2017) Overexpression and Gene Amplification of PD-L1 in Cancer Cells and PD-L1+ Immune Cells in Epstein-Barr Virus-Associated Gastric Cancer: The Prognostic Implications. ModernPathology, 30, 427-439. https://doi.org/10.1038/modpathol.2016.202
[35]
Shinozaki-Ushiku, A., Kunita, A., Isogai, M., Hibiya, T., Ushiku, T., Takada, K., etal. (2015) Profiling of Virus-Encoded Micrornas in Epstein-Barr Virus-Associated Gastric Carcinoma and Their Roles in Gastric Carcinogenesis. JournalofVirology, 89, 5581-5591. https://doi.org/10.1128/jvi.03639-14
[36]
Kondo, A., Shinozaki‐Ushiku, A., Rokutan, H., Kunita, A., Ikemura, M., Yamashita, H., etal. (2023) Loss of Viral Genome with Altered Immune Microenvironment during Tumour Progression of Epstein-Barr Virus-Associated Gastric Carcinoma. TheJournalofPathology, 260, 124-136. https://doi.org/10.1002/path.6067
[37]
Wu, L.W., Jang, S.J., Shapiro, C., Fazlollahi, L., Wang, T.C., Ryeom, S.W., etal. (2024) Diffuse Gastric Cancer: A Comprehensive Review of Molecular Features and Emerging Therapeutics. TargetedOncology, 19, 845-865. https://doi.org/10.1007/s11523-024-01097-2
[38]
Barcelo, J., Samain, R. and Sanz-Moreno, V. (2023) Preclinical to Clinical Utility of ROCK Inhibitors in Cancer. TrendsinCancer, 9, 250-263. https://doi.org/10.1016/j.trecan.2022.12.001
[39]
Zhang, F.F., Sahu, V., Peng, K., Wang, Y.C., Li, T.X., Bala, P., et al. (2024) Recurrent RhoGAP Gene Fusion CLDN18-ARHGAP26 Promotes RHOA Activation and Focal Adhesion Kinase and YAP-TEAD Signalling in Diffuse Gastric Cancer. Gut, 73, 1280-1291. https://doi.org/10.1136/gutjnl-2023-329686
[40]
Zhang, T. and Tang, X.D. (2025) Beyond Metaplasia: Unraveling the Complex Pathogenesis of Autoimmune Atrophic Gastritis and Its Implications for Gastric Cancer Risk. QJM: AnInternationalJournalofMedicine, hcaf028. https://doi.org/10.1093/qjmed/hcaf028
[41]
Sheng, W., Malagola, E., Nienhüser, H., Zhang, Z., Kim, W., Zamechek, L., etal. (2020) Hypergastrinemia Expands Gastric ECL Cells through CCK2R+ Progenitor Cells via ERK Activation. CellularandMolecularGastroenterologyandHepatology, 10, 434-449. https://doi.org/10.1016/j.jcmgh.2020.04.008
[42]
Casalino, L. and Verde, P. (2020) Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and Metastasis. Genes, 11, Article 922. https://doi.org/10.3390/genes11080922
[43]
Sullivan, B., Light, T., Vu, V. and Leckband, D. (2022) Mechanical Disruption of E-Cadherin Complexes with Epidermal Growth Factor Receptor Actuates Growth Factor-Dependent Signaling. Proceedings of the National Academy of Sciences of the United States of America, 119, e2100679119. https://doi.org/10.1073/pnas.2100679119
[44]
Joshi, S.S. and Badgwell, B.D. (2021) Current Treatment and Recent Progress in Gastric Cancer. CA: ACancerJournalforClinicians, 71, 264-279. https://doi.org/10.3322/caac.21657
[45]
Kim, H., Hwang, Y., Sung, H., Jang, J., Ahn, C., Kim, S.G., et al. (2018) Effectiveness of Gastric Cancer Screening on Gastric Cancer Incidence and Mortality in a Community-Based Prospective Cohort. CancerResearchandTreatment, 50, 582-589. https://doi.org/10.4143/crt.2017.048
[46]
Teh, J.-L., Shabbir, A., Yuen, S. and So, J.B. (2020) Recent Advances in Diagnostic Upper Endoscopy. WorldJournalofGastroenterology, 26, 433-447. https://doi.org/10.3748/wjg.v26.i4.433
[47]
Huang, Y.X., Shao, Y.F., Yu, X., Chen, C.J., Guo, J.M. and Ye, G.L. (2024) Global Progress and Future Prospects of Early Gastric Cancer Screening. JournalofCancer, 15, 3045-3064. https://doi.org/10.7150/jca.95311
[48]
Cunningham, D., Allum, W.H., Stenning, S.P., Thompson, J.N., Van de Velde, C.J.H., Nicolson, M., etal. (2006) Perioperative Chemotherapy versus Surgery Alone for Resectable Gastroesophageal Cancer. NewEnglandJournalofMedicine, 355, 11-20. https://doi.org/10.1056/nejmoa055531
[49]
Al-Batran, S., Homann, N., Pauligk, C., Goetze, T.O., Meiler, J., Kasper, S., et al. (2019) Perioperative Chemotherapy with Fluorouracil Plus Leucovorin, Oxaliplatin, and Docetaxel versus Fluorouracil or Capecitabine Plus Cisplatin and Epirubicin for Locally Advanced, Resectable Gastric or Gastro-Oesophageal Junction Adenocarcinoma (FLOT4): A Randomised, Phase 2/3 Trial. TheLancet, 393, 1948-1957. https://doi.org/10.1016/s0140-6736(18)32557-1
[50]
Hofheinz, R.D., Haag, G.M., Ettrich, T.J., Borchert, K., Kretzschmar, A., Teschendorf, C., etal. (2020) Perioperative Trastuzumab and Pertuzumab in Combination with FLOT versus FLOT Alone for HER2-Positive Resectable Esophagogastric Adenocarcinoma: Final Results of the PETRARCA Multicenter Randomized Phase II Trial of the AIO. JournalofClinicalOncology, 38, 4502-4502. https://doi.org/10.1200/jco.2020.38.15_suppl.4502
[51]
Bang, Y., Kim, Y., Yang, H., Chung, H.C., Park, Y., Lee, K.H., etal. (2012) Adjuvant Capecitabine and Oxaliplatin for Gastric Cancer after D2 Gastrectomy (CLASSIC): A Phase 3 Open-Label, Randomised Controlled Trial. TheLancet, 379, 315-321. https://doi.org/10.1016/s0140-6736(11)61873-4
[52]
Yoshida, K., Kodera, Y., Kochi, M., Ichikawa, W., Kakeji, Y., Sano, T., etal. (2019) Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients with Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial. JournalofClinicalOncology, 37, 1296-1304. https://doi.org/10.1200/jco.18.01138
[53]
Moehler, M.H., Janjigian, Y.Y., Adenis, A., Aucoin, J., Boku, N., Chau, I., etal. (2018) Checkmate 649: A Randomized, Multicenter, Open-Label, Phase III Study of Nivolumab (NIVO) + Ipilimumab (IPI) or Nivo + Chemotherapy (CTX) versus CTX Alone in Patients with Previously Untreated Advanced (Adv) Gastric (G) or Gastroesophageal Junction (GEJ) Cancer. JournalofClinicalOncology, 36, TPS192-TPS192. https://doi.org/10.1200/jco.2018.36.4_suppl.tps192
[54]
Shitara, K., Doi, T., Dvorkin, M., Mansoor, W., Arkenau, H., Prokharau, A., etal. (2018) Trifluridine/Tipiracil versus Placebo in Patients with Heavily Pretreated Metastatic Gastric Cancer (TAGS): A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. TheLancetOncology, 19, 1437-1448. https://doi.org/10.1016/s1470-2045(18)30739-3
[55]
Bang, Y., Van Cutsem, E., Feyereislova, A., Chung, H.C., Shen, L., Sawaki, A., etal. (2010) Trastuzumab in Combination with Chemotherapy versus Chemotherapy Alone for Treatment of HER2-Positive Advanced Gastric or Gastro-Oesophageal Junction Cancer (ToGA): A Phase 3, Open-Label, Randomised Controlled Trial. TheLancet, 376, 687-697. https://doi.org/10.1016/s0140-6736(10)61121-x
[56]
Zhang, M. and Yang, C.X. (2019) Research Progress on the Application Value of Narrow Band Imaging Technology in the Diagnosis of Gastric Diseases. Modern Medicine and Hygiene, 35, 2017-2020.
[57]
Fu, Y.F., Wang, B.D., He, Y.S., et al. (2024) Research Progress of Tumor Biomarkers in Liquid Biopsy of Gastric Cancer. Chinese Journal of Cancer Prevention and Treatment, 16, 673-680.
[58]
Decourtye-Espiard, L., Bougen-Zhukov, N., Godwin, T., Brew, T., Schulpen, E., Black, M.A., et al. (2021) E-Cadherin-Deficient Epithelial Cells Are Sensitive to HDAC Inhibitors. Cancers, 14, Article 175. https://doi.org/10.3390/cancers14010175
