P16 protein expression as a useful predictive biomarker for neoadjuvant chemotherapy response in patients with high-grade osteosarcoma

Tang, Yin; Yang, Changchun; Guo, Zonghui; Fu, Youwei; Yu, Xiao; Liu, Bing-Gen; Zhou, Haier; Wang, Junjie; Li, Weilong; Pang, Qiuxiang

doi:10.1097/md.0000000000006714

Cited by 11 publications

(13 citation statements)

References 37 publications

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“…Thus, the identification of osteosarcoma prognostic markers and therapeutic targets is an urgent requirement. [ 7 ] Recently, several common markers [ 8 , 9 ] have been identified correlated with the metastasis and prognosis in osteosarcoma, and proliferating cell nuclear antigen (PCNA) is a promising marker among these.…”

Section: Introductionmentioning

confidence: 99%

The prognostic value of PCNA expression in patients with osteosarcoma

Wang

Yuan

et al. 2017

Medicine

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Background:Numerous studies have attempted to determine the prognostic role of proliferating cell nuclear antigen (PCNA) expression in patients with osteosarcoma with no consistent conclusion. We performed this meta-analysis to systematically elucidate the association in a more precise manner.The purpose of this meta-analysis is to determine the prognostic role of PCNA in patients with osteosarcoma.Methods:A systematic search of relevant studies was performed in 6 electronic databases including PubMed, Embase, Web of Science, Wanfang database, China National Knowledge Internet (CNKI) database, and Chinese Biological Medical (CBM) Database (up to March 1, 2016) with the following keywords: (PCNA OR proliferating cell nuclear antigen) AND (osteosarcoma OR osteogenic tumor). A manual search of references on relevant articles was also conducted by 2 investigators independently. We performed a comprehensive evaluation of the correlation between PCNA expression and overall survival (OS) or disease-free survival (DFS) by calculating relative ratios (RR) and their corresponding 95% confidence intervals (CI) using STATA software. A fixed- or random-effect model was chosen based on the between-study heterogeneity.Results:In total, 16 studies with 691 osteosarcoma patients were included in this meta-analysis. PCNA overexpression was found in approximately 57.31% of the patients with osteosarcoma. The meta-analysis suggested that PCNA overexpression in osteosarcoma patients is associated with low OS, but not significantly with DFS (RR = 1.82, 95% CI 1.53–2.18, P = .000; RR = 1.15, 95% CI 0.91–1.44, P = 0.234). Sensitivity analysis for OS and DFS showed no significant difference and the pooled RRs were stable when the included studies were removed one by one. Similar results were also obtained for subgroup analysis based on different follow-ups and cutoffs to determine PCNA expression.Conclusion:The findings from this meta-analysis indicate that PCNA overexpression is an effective biomarker for poor prognosis in patients with osteosarcoma for OS. Hence, more large-scale studies are still needed to further warrant this conclusion.

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Section: Introductionmentioning

confidence: 99%

The prognostic value of PCNA expression in patients with osteosarcoma

Wang

Yuan

et al. 2017

Medicine

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“…In general, a good response to chemotherapy is observed in tumor cells with brisk mitosis or hypervascularity before chemotherapy 3 . However, the histological findings predictive of the efficacy of neoadjuvant chemotherapy in osteosarcoma cells are cytologic anaplasia and positive p16 expression, which differ from the high rate of mitosis and tumor necrosis in osteosarcoma [9][10][11] . Furthermore, a few novel markers, such as M2TA and miR221, have been reported to be early predictive biomarkers for the efficacy of neoadjuvant chemotherapy in osteosarcoma patients in recent years [12][13][14] .…”

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confidence: 95%

The number of osteoclasts in a biopsy specimen can predict the efficacy of neoadjuvant chemotherapy for primary osteosarcoma

Araki

Yamamoto

Hayashi

et al. 2021

Sci Rep

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Osteosarcoma is the most common primary malignant bone tumor, and its standard treatment is a combination of surgery and chemotherapy. A poor response to chemotherapy causes unfavorable oncological outcomes. We investigated the correlation between osteoclast differentiation in biopsy specimens and the efficacy of neoadjuvant chemotherapy in resected specimens. Forty-nine patients who underwent neoadjuvant chemotherapy and subsequent surgical treatment at our institution between 1999 and 2018 were enrolled. Using medical records, we investigated the age, sex, tumor size, location, subtype, staging, chemotherapy agents (doxorubicin, cisplatin, ifosfamide, and methotrexate), number of neoadjuvant chemotherapy courses, number of osteoclasts in biopsy specimens, and efficacy of neoadjuvant chemotherapy according to the Rosen and Huvos classification (Grade I-IV) in resected specimens. Univariate and multivariate analyses were performed to identify factors predictive of a good response in resected specimens after neoadjuvant chemotherapy. A good response (Grade III/IV) was detected in 25, while a poor response (Grade I/II) was detected in 24. According to the multivariate analysis, ≥ 46 years old (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.01–0.45; p < 0.01) and ≥ 5 mature osteoclasts in a biopsy specimen (OR, 36.9; 95% CI, 6.03–225; p < 0.01) were significantly associated with the neoadjuvant chemotherapy efficacy. The accuracy for predicting a good response to chemotherapy based on ≥ 5 osteoclasts in a biopsy specimen in patients < 46 years old was 85%. The number of mature osteoclasts in biopsy specimens is a simple factor for predicting the efficacy of chemotherapy before treatment, although further studies will be required to determine the underlying mechanism.

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“…Overexpression of p21 protein in OS cell line (U2OS) sensitizes these cells to apoptosis caused by cisplatin [ 36 ]. Another senescence protein marker, p16 was considered to be a predictor of the response to neoadjuvant chemotherapy in a Caucasian population of patients with high-grade OS [ 48 ]. p53 can maintain cell growth or senescence response after telomere dysfunction; its activity depends on the p16 protein level [ 49 ].…”

Section: Structure and Functions Of Tp53mentioning

confidence: 99%

TP53 in Biology and Treatment of Osteosarcoma

Synoradzki

Bartnik

Czarnecka

et al. 2021

Cancers

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The TP53 gene is mutated in 50% of human tumors. Oncogenic functions of mutant TP53 maintain tumor cell proliferation and tumor growth also in osteosarcomas. We collected data on TP53 mutations in patients to indicate which are more common and describe their role in in vitro and animal models. We also describe animal models with TP53 dysfunction, which provide a good platform for testing the potential therapeutic approaches. Finally, we have indicated a whole range of pharmacological compounds that modulate the action of p53, stabilize its mutated versions or lead to its degradation, cause silencing or, on the contrary, induce the expression of its functional version in genetic therapy. Although many of the described therapies are at the preclinical testing stage, they offer hope for a change in the approach to osteosarcoma treatment based on TP53 targeting in the future.

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P16 protein expression as a useful predictive biomarker for neoadjuvant chemotherapy response in patients with high-grade osteosarcoma

Cited by 11 publications

References 37 publications

The prognostic value of PCNA expression in patients with osteosarcoma

The prognostic value of PCNA expression in patients with osteosarcoma

The number of osteoclasts in a biopsy specimen can predict the efficacy of neoadjuvant chemotherapy for primary osteosarcoma

TP53 in Biology and Treatment of Osteosarcoma

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