Abstract
Recently, we read the article “P16INK4a overexpression and survival in osteosarcoma patients: a meta analysis” by Jie Bu and his colleagues, published in the recent issue of International Journal Of Experimental Pathology. This research performed a meta-analysis to uncover the role of P16INK4a expression in overall survival rate in patients with osteosarcoma. The investigators concluded as follows: (i) the pateints with overexpression of P16INK4a had a longer overall survival rate than that with loss expression of P16INK4a; (ii) P16INK4a was an effective biomarker of prognosis in patients with osteosarcoma.The findings are valubale and encouraging. However, some flaws and imperfections rooted in this work.
Keywords: Osteosarcoma, meta-analysis, P16INK4a
Firstly, the investigators displayed the search only in PubMed, Embase, web of science and CNKI (China National Knowledge Infrastructure) [1]. The limited electronic databases would compromise the final conclusion. The common sources for meta-analysis are PubMed, Embase and Cochrane Central Register of Controlled Trials. Meanwhile, the investigators searched the CNKI, a Chinese database not a common candidate source for meta-analysis. Five included articles are from this database, which is not normal [2-6]. In addition, the investigators just presented the search strategy by using the keywords such as “osteosarcoma” or “osteosarcomas” and “p16” or “P16INK4a”. The specific search strategies and the process of paper included or excluded were not well clearly clarified. To make readers more well understanding this meta-analysis, we suggest the investigators should provide the detailed flow chart in the article.
Secondly, the investigators included the eight eligible articles with total 354 patients with osteosarcoma. However, the characteristics of the enrolled studied was not listed in this article. We advise that the number and demographics of patients included, number of patients with high or loss expression of P16INK4a and survival rate should be provided to assist us in understanding the meta-analysis well.
Thirdly, the standard criteria of positive/negative expression of P16INK4a among the included studies is different [2,6-8], which leads to the heterogenicity at baseline. Moreover, some enrolled patients with osteosarcoma underwent chemotherpy while others did not, which may confound the outcome [2,4,7,8]. As the chemotherapy may have a effect on expression of P16INK4a in patients with osteosarcoma. We suggest that only studies which analyze the untreated diagnostic samples should be included.
Fourthly, the investigators did not evaluate the quality of the included studies. It is well known that a convicing and persusasive meta-analysis is supported by high quality controlled clincial trials and randomized controlled trials. Therefore, we hope the authors can perform the analysis on the methodological issues.
Eventually, more well-designed and large-scale studies are required to further verify the prognostic role of P16INK4a expression on patients with osteosarcoma.
Disclosure of conflict of interest
None.
References
- 1.Bu J, Li H, Liu LH, Ouyang YR, Guo HB, Li XY, Xiao T. P16INK4a overexpression and survival in osteosarcoma patients: a meta analysis. Int J Clin Exp Pathol. 2014;7:6091–6096. [PMC free article] [PubMed] [Google Scholar]
- 2.Xiao Z, Cai Y, Lin Q. Preliminary research on the expression of rumor suppressor gene p16 protein in human osteosarcoma. Zhejiang Clin Med J. 2000:653–654. [Google Scholar]
- 3.Li L, Wang Y, Liu Y, Li Z. Clinical signification of express of tumor supressor genes and proliferative in osteosarcoma. J Clin Orthop. 1999:164–166. [Google Scholar]
- 4.Meng L, Yu X, Du D, Wang G. The expression and significance of the P16 gene in osteosarcoma. Shandong Med J. 1999:19–20. [Google Scholar]
- 5.Lei N, Pan X, Qi Y, Fang Y. Expressions of P16 and proliferating cell nuclear antigen in osteosarcoma and clinical significances. J Jilin Univ-Med. 2009:519–521. [Google Scholar]
- 6.Li W, Zhao J, Pi G. P16 gene exppression and clinical significance in human osteosarcoma [article in Chinese] . J Chin Pract Diag Ther. 2005;483-484:487. [Google Scholar]
- 7.Maitra A, Roberts H, Weinberg AG, Geradts J. Loss of p16 (INK4a) expression correlates with decreased survival in pediatric osteosarcomas. Int J Cancer. 2001;95:34–38. doi: 10.1002/1097-0215(20010120)95:1<34::aid-ijc1006>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
- 8.Mohseny AB, Szuhai K, Romeo S, Buddingh EP, Briaire-de Bruijn I, de Jong D, van Pel M, Cleton-Jansen AM, Hogendoorn PC. Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2. J Pathol. 2009;219:294–305. doi: 10.1002/path.2603. [DOI] [PubMed] [Google Scholar]