Observational study (cohort type) of advanced GC patients that will be recruited prospectively to study biological factors associated with the disease and relevant clinical outcomes.

Despite of multiple attempts to improve treatment in recent decades, none strategies has improved prognosis in locally advanced stage III and IV GC. A therapeutic approach to GC based on current histological and image criteria (Tumour Node Metastasis -TNM- stage) is insufficient. Although multiple targeted agents are currently under investigation, so far, only trastuzumab and ramucirumab have demonstrated efficacy in advanced GC and have a regulatory approval. For this reason, the identification of specific targets that could be susceptible for drug inhibition, is an urgent requirement. Moreover, most studies and current international databases on late-stage/advanced GC are largely based on Asian populations, in sharp contrast tumour biology and genome of EU or CELAC populations remain poorly known.

The primary objective of this study are to:

1. Characterize a multi-centric cohort including EU and CELAC populations diagnosed with advanced GC through a multi-omic approach including proteomics, genomics, transcriptomics, microbiome and exposome analysis due to study the determinants of GC.
2. Identify the regional differences in EU and CELAC populations recruiting patients for this study for each omic characterization due to identify the high-risk group populations.
3. Identify and select from the multi-omic approach those biomarkers useful for the development of an algorithm to guide the therapeutic approach for advanced GC.

Cases:

• Inclusion criteria:

  • Subjects ≥18 years old.
  • GC diagnosis stages III and IV (including gastroesophageal junction cancer) and/or a gastroscopy indication due to the high diagnostic suspicion of GC as part of the study of his disease.
  • Has given and signed the IC to participate in this study.

• Exclusion criteria:

  • Patients diagnosed with GC early disease (stage I and II) suitable for resectable strategy.

• Withdrawal criteria:

  • Patients initially recruited with high suspicion of GC diagnosis but not confirmed by the pathological report.

Controls:

• Inclusion criteria (only for microbiome analysis):

  • Subjects ≥18 years old.
  • Subjects to whom a gastroscopy is indicated within clinical care and is confirmed absent of GC in the same centres will be matched in age (+/- 10 years), gender and pertaining from the same region of the GC case.
  • Has given and signed the IC to participate in this study.

• Exclusion criteria:

  • Subjects from a different geographic area from the cases.
  • Patients with high suspicion of GC.
  • Patients with previous histopathologic diagnosis of peptic (gastric or duodenal) ulcer disease and/or atrophy or intestinal metaplasia.
  • Patients that have received antimicrobials during the 4 weeks period prior to the endoscopy.
  • Patients that have received proton pump inhibitors or H2-receptor antagonists, at least 2 weeks prior to the endoscopy

• Subjects >18 years old, with high diagnostic suspicion of advanced GC diagnosis (Stage III and IV)
• Subjects >18 years old to whom a gastroscopy was indicated and confirmed absent of GC.