This　study　aimed　to　identify　key　genes　associated　with　post-chemotherapy　recurrence　in　gastric　cancer　patients.　Gene　expression　data　from　multiple　cohorts　were　analysed　to　determine　differentially　expressed　genes　between　recurrent　and　non-recurrent　cases.　A　prognostic　risk　model　incorporating　COL8A1,　HSPB7　and　SLIT2　was　developed　and　validated　across　six　independent　cohorts.　The　risk　score　demonstrated　significant　associations　with　disease-free　and　overall　survival,　tumour　grade　and　molecular　subtypes.　Notably,　the　risk　score　showed　potential　as　a　predictor　of　immunotherapy　response,　outperforming　established　markers　such　as　microsatellite　instability　score　and　Epstein-Barr　virus　status.　Analysis　of　the　tumour　immune　microenvironment　revealed　a　correlation　between　risk　score　and　M2　macrophage　infiltration.　A　nomogram　integrating　the　risk　score　with　clinical　factors　demonstrated　high　accuracy　in　predicting　patient　survival.　Further　investigation　of　COL8A1　revealed　its　significant　role　in　gastric　cancer　cell　proliferation,　metastasis,　and　chemoresistance.　In　vitro　and　in　vivo　experiments　showed　that　COL8A1　knockdown　inhibited　cancer　cell　growth,　invasion,　and　metastasis　while　enhancing　chemosensitivity.　These　findings　provide　valuable　insights　into　the　molecular　mechanisms　of　gastric　cancer　recurrence　and　offer　potential　biomarkers　for　prognosis　and　treatment　response　prediction.　The　study　highlights　the　importance　of　integrating　genomic　data　with　clinical　information　to　improve　patient　stratification　and　personalised　treatment　strategies　in　gastric　cancer　management.