LP Sydorchuk, Ruslan Gumennyi, Andrii Sydorchuk, I.V. Batih, Valentina Vasiuk, Ruslan Sydorchuk, Iryna Kamyshna, Pavlo Petakh, Iryna Halabitska, Oleksandr Kamyshnyi
Objectives: The objective of the study was to investigate the mRNA expression of critical gene patterns, including IL-6, CCL2, IL-10, MAPK1, MAPK8, MMP9, COL1A1, COL3A1, and TGFB1, and their associations with adverse postoperative outcomes in reconstructive and plastic surgery patients, depending on age. Methods: A total of 95 women participated in this prospective longitudinal cohort study and underwent reconstructive/plastic surgery. The mean age was 35.48 ± 6.61 years (range: 19–57). mRNA expression of IL-6, CCL2, IL-10, MAPK1, MAPK8, MMP9, COL1A1, COL3A1, and TGFB1 genes was evaluated in peripheral blood leukocytes using a PCR-based method with reverse transcription of cDNA. Results: The risk of postoperative complications significantly increased with elevated expression levels of IL-6 and COL3A1 (7.5-fold, p = 0.007), CCL2 (6.2-fold, p = 0.012), and MAPK1 (25.5-fold, p < 0.001). Increased expression of MAPK8, IL-10, and MMP9 was associated with a 13.2-fold higher risk (p < 0.001). The strongest association was observed for COL1A1 overexpression, which increased complication risk by 58.33-fold (p < 0.001). Risk stratification using the Molecular Complication Risk Index (MCRI), incorporating weighted gene contributions, identified an unfavorable molecular profile predominantly among women aged ≥ 40 years. Receiver operating characteristic analysis confirmed the model’s discriminative ability (AUC = 0.78; 95% CI 0.68–0.87), with an optimal cut-off value of MCRI ≥ 8.5 (sensitivity 76%, specificity 71%, p < 0.05). Conclusions: The transcriptional activity of IL-6, CCL2, IL-10, MAPK1, MAPK8, MMP9, COL1A1, COL3A1, and TGFB1 is associated with postoperative wound healing risk. Women aged over 40 years are at the highest risk of complications. Implementation of the MCRI model may enable early identification of high-risk patients, support targeted preventive strategies, and improve personalized surgical planning.