Abstract
Purpose
The PIWI-interacting RNA machinery in malignant melanoma (MM) has not been sufficiently studied. We aimed to investigate the PIWIL3 expression profiles in primary melanomas and metastases of MM including a correlation with clinical data.
Methods
We studied 161 primary melanomas, 45 lymph node metastases, and 16 distant metastases of 183 patients with MM. We used immunohistochemistry to assess PIWIL3 protein expression in situ. The relationship between the immunoreactivity of PIWIL3 and clinical data was statistically evaluated.
Results
We observed a significantly (P = 0.000059) higher median immunoreactivity score in primary melanomas (4.9; range, 0.1–6), lymph node metastases (5.1; range, 3.3–6), and distant metastases (5.6; range, 4.5–6). PIWIL3 was expressed significantly higher (P = 0.0002) in primary nodular melanomas and acral melanomas (5.2; range, 3.4–6) when compared to other melanoma subtypes (4.7; range, 0.1–6). On univariate analysis, a significant positive correlation was observed between primary melanoma PIWIL3 expression and tumor thickness (r = 0.2; P = 0.014). On univariate and multivariate analysis, PIWIL3 did not prove to be an independent predictor for melanoma relapse or death.
Conclusions
Our data indicate that PIWIL3 protein expression is elevated in more aggressive primary MM and metastatic disease. As also observed in other malignancies, PIWIL3 seems to play a role in MM progression.
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References
Alamodi AA et al (2016) Cancer stem cell as therapeutic target for melanoma treatment. Histol Histopathol. doi:10.14670/HH-11-791
Assumpcao CB et al (2015) The role of piRNA and its potential clinical implications in cancer. Epigenomics 7:975–984. doi:10.2217/epi.15.37
Balch CM et al (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27:6199–6206. doi:10.1200/JCO.2009.23.4799
Bamezai S, Rawat VP, Buske C (2012) Concise review: the Piwi-piRNA axis: pivotal beyond transposon silencing. Stem Cells 30:2603–2611. doi:10.1002/stem.1237
Chen Y, Li C, Tan C, Liu X (2016) Circular RNAs: a new frontier in the study of human diseases. J Med Genet 53:359–365. doi:10.1136/jmedgenet-2016-103758
Han BW, Zamore PD (2014) piRNAs. Curr Biol 24:R730–R733. doi:10.1016/j.cub.2014.07.037
Iliev R et al (2016) Decreased expression levels of PIWIL1, PIWIL2, and PIWIL4 are associated with worse survival in renal cell carcinoma patients. Onco Targets Ther 9:217–222. doi:10.2147/OTT.S91295
Kneitz S, Mishra RR, Chalopin D, Postlethwait J, Warren WC, Walter RB, Schartl M (2016) Germ cell and tumor associated piRNAs in the medaka and Xiphophorus melanoma models. BMC Genom 17:357. doi:10.1186/s12864-016-2697-z
Krishnan P, Ghosh S, Graham K, Mackey JR, Kovalchuk O, Damaraju S (2016) Piwi-interacting RNAs and PIWI genes as novel prognostic markers for breast cancer. Oncotarget. doi:10.18632/oncotarget.9272
Parmiani G (2016) Melanoma cancer stem cells: markers and functions. Cancers (Basel). doi:10.3390/cancers8030034
Pekarsky Y et al (2016) Dysregulation of a family of short noncoding RNAs, tsRNAs, in human cancer. Proc Natl Acad Sci USA 113:5071–5076. doi:10.1073/pnas.1604266113
Sand M (2014) The pathway of miRNA maturation. Methods Mol Biol 1095:3–10. doi:10.1007/978-1-62703-703-7_1
Sand M, Gambichler T, Sand D, Skrygan M, Altmeyer P, Bechara FG (2009) MicroRNAs and the skin: tiny players in the body’s largest organ. J Dermatol Sci 53:169–175. doi:10.1016/j.jdermsci.2008.10.004
Sasaki T, Shiohama A, Minoshima S, Shimizu N (2003) Identification of eight members of the Argonaute family in the human genome. Genomics 82:323–330
Sebastian C (2014) Tracking down the origin of cancer: metabolic reprogramming as a driver of stemness and tumorigenesis. Crit Rev Oncog 19:363–382
Suzuki R, Honda S, Kirino Y (2012) PIWI expression and function in cancer. Front Genet 3:204. doi:10.3389/fgene.2012.00204
Tan BT, Park CY, Ailles LE, Weissman IL (2006) The cancer stem cell hypothesis: a work in progress. Lab Invest 86:1203–1207. doi:10.1038/labinvest.3700488
Wang Y, Liu Y, Shen X, Zhang X, Chen X, Yang C, Gao H (2012) The PIWI protein acts as a predictive marker for human gastric cancer. Int J Clin Exp Pathol 5:315–325
Wang X et al (2015) MILI, a PIWI family protein, inhibits melanoma cell migration through methylation of LINE1. Biochem Biophys Res Commun 457:514–519. doi:10.1016/j.bbrc.2015.01.007
Wick MR, Gru AA (2016) Metastatic melanoma: pathologic characterization, current treatment, and complications of therapy. Semin Diagn Pathol 33:204–218. doi:10.1053/j.semdp.2016.04.005
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This study conforms to the applicable local requirements regarding ethical and investigational committee review, informed consent, and other statutes or regulations regarding the protection of the rights and welfare of human subjects participating in medical research (Ethical Review Board of the Ruhr-University Bochum, Germany).
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Gambichler, T., Kohsik, C., Höh, AK. et al. Expression of PIWIL3 in primary and metastatic melanoma. J Cancer Res Clin Oncol 143, 433–437 (2017). https://doi.org/10.1007/s00432-016-2305-2
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DOI: https://doi.org/10.1007/s00432-016-2305-2