Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 10 06 1 16 Xinyao Zhou Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School, Nanjing University, Nanjing, China Min Liu Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School, Nanjing University, Nanjing, China Xiaojiao Zheng Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School, Nanjing University, Nanjing, China Yong Lu Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School, Nanjing University, Nanjing, China 2026 04 10 2026 06 04 This study examined age-related immune infiltration and repair-associated molecular abnormalities in oral cancer using public datasets and explored their potential relevance to submental island flap (SIF) reconstruction. GEO datasets GSE30784, GSE41613, GSE25099, and GSE37991 were analyzed. Repair-associated candidate genes were selected from literature on flap survival, ischemia–reperfusion injury, wound healing, angiogenesis, inflammation, and matrix remodeling. Differential expression was assessed in GSE30784, followed by screening incorporating age-related trends and prognostic information in GSE41613. Because ages were reported as intervals, findings were interpreted as older-age-related trends rather than results from a strictly defined elderly cohort. External and paired validation used GSE25099 and GSE37991, respectively. Associations with immune infiltration were also examined. Five key genes—ANGPT2, HIF1A, VEGFC, TGFB1, and MMP9—were identified; IL1B and IL6 were retained for supplementary analysis. All five genes were upregulated in tumor tissues, with consistent findings across validation datasets. In GSE41613, the genes were associated with prognosis, and a higher combined expression score corresponded to poorer overall survival. ANGPT2, HIF1A, VEGFC, and TGFB1 generally correlated positively with myeloid inflammatory features, whereas MMP9 showed a stronger association with M2 macrophage infiltration. These findings suggest repair-associated molecular and immune abnormalities potentially relevant to SIF reconstruction. The five genes warrant investigation as candidate markers of the local repair microenvironment; their relevance to flap outcomes requires direct clinical validation. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4790 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4790/2435