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Current biomarkers lack sensitivity for early detection. Interleukin-8 (IL-8), a pro-inflammatory chemokine implicated in H. pylori-associated gastric carcinogenesis, has not been rigorously evaluated in longitudinal studies for its ability to predict malignant progression in patients with precancerous lesions. Aim: To investigate whether serial serum IL-8 measurements predict progression to gastric cancer among Egyptian patients with H. pylori-associated atrophic gastritis and intestinal metaplasia over 24 months of follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>a prospective, longitudinal biomarker, multicenter cohort study enrolled 200 participants across 5 Egyptian centers: 50 with atrophic gastritis, 50 with intestinal metaplasia, 25 with H. pylori-positive gastric cancer, 25 with H. pylori-negative gastric cancer, and 50 healthy controls. All underwent baseline clinical assessment, laboratory evaluation (including CEA, CA19-9), H. pylori testing (stool antigen and urea breath test per Maastricht VI), and endoscopy with histopathology (Updated Sydney System). Patients with precancerous lesions were followed for 24 months with serial IL-8 measurements at 0, 6, 12, 18, and 24 months, and repeat endoscopy at study completion. Group-based trajectory modeling was performed blinded to outcome status. Multivariable logistic regression with penalization was used due to low event count. Time-dependent ROC analysis used a cumulative\/dynamic approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 100 patients with precancerous lesions, 94 completed follow-up, and 9 progressed to gastric cancer (7 from intestinal metaplasia, 2 from atrophic gastritis). Baseline IL-8 levels demonstrated a progressive increase across groups (controls: 9.7\u2009\u00b1\u20093.2 pg\/mL; atrophic gastritis: 42.1\u2009\u00b1\u200911.8; intestinal metaplasia: 64.8\u2009\u00b1\u200914.3; gastric cancer: 107.4\u2009\u00b1\u200924.6;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). IL-8 elevation in gastric cancer was independent of H. pylori status across all stages (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.50 for all stage-stratified comparisons, though these subgroup analyses are limited by small sample sizes and may be considered exploratory). Baseline IL-8\u2009&gt;\u200952.3 pg\/mL was associated with progression risk, AUC 0.84, sensitivity 88.9%, specificity 78.0%, and negative predictive value 98.5%, significantly outperforming CEA (AUC 0.62) and CA19-9 (AUC 0.58). Time-dependent AUC increased to 0.91 at 12 months and 0.94 at 18 months. Trajectory modeling, performed blinded to outcome, identified three patterns: Stable-Low (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200942), Moderate-Rising (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200949), and High-Accelerating (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099). The acceleration point in the High-Accelerating group preceded clinical cancer diagnosis by a median of 6 months (range 3\u201312), however, this exploratory finding requires external validation. In multivariable analysis using Firth penalized regression, baseline IL-8 (aOR per 10 pg\/mL: 2.31, 95% CI: 1.48\u20133.61,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and intestinal metaplasia (aOR: 4.22, 95% CI: 1.31\u201313.61,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.016) were independently associated with progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In this prospective longitudinal biomarker study, serial serum IL-8 trajectories were significantly associated with progression from H. pylori\u2013associated precancerous lesions to gastric cancer. Rising IL-8 levels preceded clinical diagnosis by approximately 6\u201312 months, suggesting potential utility for risk stratification. A Baseline IL-8\u2009&gt;\u200952.3 pg\/mL was independently associated with progression (adjusted HR: 6.94,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), but this exploratory trajectory is hypothesis-generating and requires external validation before causal interpretation. However, these findings are exploratory and hypothesis-generating.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13099-026-00876-8","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:35:01Z","timestamp":1790141701000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serial serum interleukin-8 trajectories are associated with progression from Helicobacter pylori\u2013associated precancerous lesions to gastric cancer: a prospective longitudinal cohort study"],"prefix":"10.1186","volume":"18","author":[{"given":"Atteyat A.","family":"Semeya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raafat S. 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