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      The role of CD147 expression in prostate cancer: a systematic review and meta-analysis

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          Abstract

          Background

          There are a number of studies which show that expression of CD147 is increased significantly in prostate cancer (PCa). However, conflicting conclusions have also been reported by other researchers lately. In order to arrive at a clear conclusion, a meta-analysis of eligible studies was conducted.

          Materials and methods

          We searched PubMed, MEDLINE, Cochrane Library, and the China National Knowledge Infrastructure databases to identify all the published case–control studies on the relationship between the expression of CD147 and PCa until February 2016. In the end, a total of 930 patients in eight studies were included in the meta-analysis.

          Results

          CD147 expression in the PCa patients increased significantly (odds ratio [OR], 4.65; 95% confidence interval [CI], 3.52–6.14; Z=10.79; P<0.05), but there was obvious heterogeneity between studies ( I 2=92.9%, P<0.05). Subgroup analysis showed that positive expression of CD147 was associated with PCa among the Asian population (OR, 21.01; 95% CI, 12.88–34.28; Z=12.19; P<0.05). Furthermore, it was significantly related to TNM stage (OR, 0.24; 95% CI, 0.17–0.35; Z=7.74; P<0.05), Gleason score (OR, 0.41; 95% CI, 0.31–0.56; Z=5.62; P<0.05), differentiation grade (OR, 0.27; 95% CI, 0.13–0.56; Z=3.47; P<0.05), and pretreatment serum prostate-specific antigen level (OR, 0.07; 95% CI, 0.03–0.16; Z=6.47; P<0.05).

          Conclusion

          Positive expression of CD147 was related to PCa, significant heterogeneity was not found between Asian studies, and the result became more significant. The positive expression of CD147 was significantly related to the clinicopathological characteristics of PCa. This suggests that CD147 plays an essential role in poor prognosis and recurrence prediction.

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          Most cited references 26

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          Quantifying the impact of between-study heterogeneity in multivariate meta-analyses

          Measures that quantify the impact of heterogeneity in univariate meta-analysis, including the very popular I 2 statistic, are now well established. Multivariate meta-analysis, where studies provide multiple outcomes that are pooled in a single analysis, is also becoming more commonly used. The question of how to quantify heterogeneity in the multivariate setting is therefore raised. It is the univariate R 2 statistic, the ratio of the variance of the estimated treatment effect under the random and fixed effects models, that generalises most naturally, so this statistic provides our basis. This statistic is then used to derive a multivariate analogue of I 2, which we call . We also provide a multivariate H 2 statistic, the ratio of a generalisation of Cochran's heterogeneity statistic and its associated degrees of freedom, with an accompanying generalisation of the usual I 2 statistic, . Our proposed heterogeneity statistics can be used alongside all the usual estimates and inferential procedures used in multivariate meta-analysis. We apply our methods to some real datasets and show how our statistics are equally appropriate in the context of multivariate meta-regression, where study level covariate effects are included in the model. Our heterogeneity statistics may be used when applying any procedure for fitting the multivariate random effects model. Copyright © 2012 John Wiley & Sons, Ltd.
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            The complexity of prostate cancer: genomic alterations and heterogeneity.

            Although prostate cancer is the most common malignancy to affect men in the Western world, the molecular mechanisms underlying its development and progression remain poorly understood. Like all cancers, prostate cancer is a genetic disease that is characterized by multiple genomic alterations, including point mutations, microsatellite variations, and chromosomal alterations such as translocations, insertions, duplications, and deletions. In prostate cancer, but not other carcinomas, these chromosome alterations result in a high frequency of gene fusion events. The development and application of novel high-resolution technologies has significantly accelerated the detection of genomic alterations, revealing the complex nature and heterogeneity of the disease. The clinical heterogeneity of prostate cancer can be partly explained by this underlying genetic heterogeneity, which has been observed between patients from different geographical and ethnic populations, different individuals within these populations, different tumour foci within the same patient, and different cells within the same tumour focus. The highly heterogeneous nature of prostate cancer provides a real challenge for clinical disease management and a detailed understanding of the genetic alterations in all cells, including small subpopulations, would be highly advantageous.
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              Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer

              Background Monocarboxylate transporters (MCTs) are transmembrane proteins involved in the transport of monocarboxylates across the plasma membrane, which appear to play an important role in solid tumours, however the role of MCTs in prostate cancer is largely unknown. The aim of the present work was to evaluate the clinico-pathological value of monocarboxylate transporters (MCTs) expression, namely MCT1, MCT2 and MCT4, together with CD147 and gp70 as MCT1/4 and MCT2 chaperones, respectively, in prostate carcinoma. Methods Prostate tissues were obtained from 171 patients, who performed radical prostatectomy and 14 patients who performed cystoprostatectomy. Samples and clinico-pathological data were retrieved and organized into tissue microarray (TMAs) blocks. Protein expression was evaluated by immunohistochemistry in neoplastic (n = 171), adjacent non-neoplastic tissues (n = 135), PIN lesions (n = 40) and normal prostatic tissue (n = 14). Protein expression was correlated with patients' clinicopathologic characteristics. Results In the present study, a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue. All MCT isoforms and CD147 were expressed in PIN lesions. Importantly, for MCT2 and MCT4 the expression levels in PIN lesions were between normal and tumour tissue, which might indicate a role for these MCTs in the malignant transformation. Associations were found between MCT1, MCT4 and CD147 expressions and poor prognosis markers; importantly MCT4 and CD147 overexpression correlated with higher PSA levels, Gleason score and pT stage, as well as with perineural invasion and biochemical recurrence. Conclusions Our data provides novel evidence for the involvement of MCTs in prostate cancer. According to our results, we consider that MCT2 should be further explored as tumour marker and both MCT4 and CD147 as markers of poor prognosis in prostate cancer.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2016
                01 August 2016
                : 10
                : 2435-2442
                Affiliations
                [1 ]Department of Laboratory Medicine, Xijing Hospital, Fourth Military Medical University
                [2 ]Department of Clinical Laboratory, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, People’s Republic of China
                Author notes
                Correspondence: Xiao-Ke Hao, Department of Laboratory Medicine, Xijing Hospital, Fourth Military Medical University, 15 Changle West Road, Xi’an 710032, Shaanxi Province, People’s Republic of China, Tel +86 29 8477 5572, Fax +86 29 8427 7393, Email haoxkg@ 123456126.com
                [*]

                These authors contributed equally to this work

                Article
                dddt-10-2435
                10.2147/DDDT.S111155
                4975147
                27536064
                © 2016 Ye et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine

                cd147, prostate cancer, meta-analysis

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