P16 protein expression as a useful predictive biomarker for neoadjuvant chemotherapy response in patients with high-grade osteosarcoma: A systematic meta-analysis under guideline of PRISMA

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Neoadjuvant chemotherapy for patients with high-grade osteosarcoma has highly improved the clinical survival. However, the prognostic and predictive role of P16 expression after neoadjuvant chemotherapy remains unclear. We first determined whether P16 expression can become a potential prognostic and predictive biomarker in high-grade osteosarcoma.


This meta-analysis was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. Eligible studies were pooled and the overall odds ratios (ORs) and hazard ratios (HRs) with the corresponding 95% confidence intervals (95% CIs) were calculated in this analysis.


Four studies involving a total of 527 patients with high-grade osteosarcoma receiving neoadjuvant chemotherapy were identified. We did not find that P16 expression was correlated with sex status, histologic subtype, and tumor site (P > .1). P16 expression was found to be significantly associated with a “good” response to neoadjuvant chemotherapy (OR = 4.69, P < .001). A significant relationship was observed between p16 expression and pathologic complete response after neoadjuvant chemotherapy using multivariate analysis (OR = 9.63, P = .001). The expression of the P16 was not associated with clinical outcomes in overall survival (OS) and disease-free survival (DFS) by multivariate analysis (OS: P = .448; DFS: P = .263).


The use of P16 expression could become a promising predictive biomarker of the response to neoadjuvant chemotherapy in the white population with high-grade osteosarcoma. However, it was not correlated with the prognosis of patients in OS and DFS. More clinical researches are very essential in Asians in the future.

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