Abstract
BackgroundWhether increased expression of the tumor suppressor protein p53 indicates a p53 gene mutation in hepatocellular carcinoma (HCC) remains unclear. We conducted a meta-analysis to determine whether p53 protein overexpression detected by immunohistochemistry (IHC) offers a diagnostic prediction for p53 gene mutations in HCC patients.MethodsSystematic literature searches were conducted with an end date of December 2015. A meta-analysis was performed to estimate the diagnostic accuracy of IHC-determined p53 protein overexpression in the prediction of p53 gene mutations in HCC. Sensitivity, subgroup, and publication bias analyses were also conducted.ResultsThirty-six studies were included in the meta-analysis. The results showed that the overall sensitivity and specificity for IHC-determined p53 overexpression in the diagnostic prediction of p53 mutations in HCC were 0.83 (95% CI: 0.80–0.86) and 0.74 (95% CI: 0.71–0.76), respectively. The summary positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 2.65 (95% CI: 2.21–3.18) and 0.36 (95% CI: 0.26–0.50), respectively. The diagnostic odds ratio (DOR) of IHC-determined p53 overexpression in predicting p53 mutations ranged from 0.56 to 105.00 (pooled, 9.77; 95% CI: 6.35–15.02), with significant heterogeneity between the included studies (I2 = 40.7%, P = 0.0067). Moreover, subgroup and sensitivity analyses did not alter the results of the meta-analysis. However, potential publication bias was present in the current meta-analysis.ConclusionThe upregulation of the tumor suppressor protein p53 was indeed linked to p53 gene mutations. IHC determination of p53 overexpression can predict p53 gene mutations in HCC patients.
Highlights
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, and the cancer-related deaths due to this condition are increasing [1,2]
The results showed that the overall sensitivity and specificity for IHC-determined p53 overexpression in the diagnostic prediction of p53 mutations in hepatocellular carcinoma (HCC) were 0.83 and 0.74, respectively
The summary positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 2.65 and 0.36, respectively
Summary
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, and the cancer-related deaths due to this condition are increasing [1,2]. Elucidating the malignant biological features of HCC is critical for outcome prediction in patients with this disease. Mutations in the tumor suppressor gene p53 are the most common genetic changes in human malignancies. Aberrations of the p53 gene have been shown to be prognostic indicators associated with recurrence-free survival and overall survival in HCC patients [3,8]. Whether increased expression of the tumor suppressor protein p53 indicates a p53 gene mutation in hepatocellular carcinoma (HCC) remains unclear. We conducted a meta-analysis to determine whether p53 protein overexpression detected by immunohistochemistry (IHC) offers a diagnostic prediction for p53 gene mutations in HCC patients
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