Relationship between Ki-67 and P53 immunohistochemical expression and osteosarcoma chemotherapy sensitivity and long-term prognosis.

OBJECTIVE: To identify biomarkers predictive of chemotherapy sensitivity and prognosis in patients with osteosarcoma. METHODS: This retrospective case-control study included 237 primary osteosarcoma patients (aged 13-30 years) treated at Ningbo No.6 Hospital between 2000 and 2019. All patients received neoadjuvant chemotherapy (methotrexate/doxorubicin/cisplatin) followed by tumor resection. Chemotherapy response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Based on RECIST criteria, patients were categorized into a high-sensitivity group (n=120; complete or partial response) or a low-sensitivity group (n=117; stable or progressive disease). Long-term prognosis was defined as good (postoperative survival ≥36) or poor (<36 months). Demographic, clinical, and laboratory variables, including inflammatory markers, tumor biomarkers, and p53/Ki-67 expression, were compared. Independent predictors were identified by multivariate logistic regression for chemotherapy sensitivity and Cox proportional hazards regression for long-term prognosis. RESULTS: In the high-sensitivity group, post-treatment levels of inflammatory markers - including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), platelet-to-lymphocyte ratio (PLR) - as well as isocitrate dehydrogenase 1 (IDH1) mutation frequency, lactate dehydrogenase (LDH), and Ki-67 expression were significantly lower compared to the low-sensitivity group (all P<0.05). Multivariate analyses confirmed that lower levels of CRP (Odds Ratio [OR]=0.766; 95% CI: 0.614-0.956), IL-6 (OR=0.889; 95% CI: 0.822-0.961), TNF-α (OR=0.908; 95% CI: 0.833-0.989), PLR (OR=0.975; 95% CI: 0.959-0.992), IDH1 mutation status (OR=0.005; 95% CI: 0.001-0.359), LDH (OR=0.965; 95% CI: 0.937-0.993), and Ki-67 (OR=0.922; 95% CI: 0.861-0.988) were independent predictors of higher chemotherapy sensitivity (all P<0.05). Additionally, these factors, along with lower Ki-67 expression, were independently associated with better long-term prognosis by Cox regression analysis. CONCLUSION: Lower levels of select inflammatory markers, IDH1 mutation status, LDH, and Ki-67 expression were independently associated with increased chemotherapy sensitivity and improved prognosis in osteosarcoma. These biomarkers may aid in risk stratification and therapeutic decision-making for affected patients.