New biomarkers for differentiating renal neoplasms with eosinophilic cytoplasm: DARS2, reelin, and enkurin
Protein markers for differential diagnosis of renal neoplasms
Keywords:
chromophobe renal cell carcinoma, eosinophilic variant clear cell renal cell carcinoma, oncocytoma, DARS2, reelin, enkurinAbstract
Background/Aim: Chromophobe renal cell carcinoma (CRCC), eosinophilic variant clear cell RCC, and oncocytomas are renal neoplasms with eosinophilic cytoplasm, and their differential diagnosis is challenging despite significant advances in molecular pathology. Although many biomarkers have been identified for the differential diagnosis of these neoplasms, specific markers have not yet been reported. No studies were found in the literature on the relationship between these tumors and the new molecules DARS2, reelin, and enkurin. This paper aims to determine the roles of these proteins in renal neoplasms with eosinophilic cytoplasm.
Methods: The study retrospectively analyzed 30 EC RCC, 30 CRCC, and 30 oncocytoma cases, evaluated among renal neoplasms with eosinophilic cytoplasm, independent of demographic characteristics, in the Fırat University Medical Pathology Laboratory between 2012 and 2022. The most representative samples of the tumor were selected for each group, and the expression of DARS2, reelin, and enkurin proteins was evaluated by the immunohistochemical method.
Results: The histoscore of DARS2 expression was highest in EC RCC and least in CRCC. DARS2 was seen to differentiate CRCC from oncocytoma and EC RCC. The histoscore of reelin and enkurin protein expression was highest in oncocytoma and lowest in ECRCC. The difference between the groups was statistically significant (P<0.05).
Conclusion: DARS2 can be a useful biomarker for differentiating CRCC from EC RCC and oncocytoma, and enkurin and reelin can differentiate among these three groups.
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Motzer RJ, Jonasch E, Agarwal N, et al. Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15(6):804–34. DOI: https://doi.org/10.6004/jnccn.2017.0100
Lam JS, Klatte T, Kim HL, et al. Prognostic factors and selection for clinical studies of patients with kidney cancer. Crit Rev Oncol Hematol. 2008;65(3):235–62. DOI: https://doi.org/10.1016/j.critrevonc.2007.08.003
Eichelberg C, Junker K, Ljungberg B, Moch H. Diagnostic and prognostic molecular markers for renal cell carcinoma: a critical appraisal of the current state of research and clinical applicability. Eur Urol. 2009;55(4):851–63. DOI: https://doi.org/10.1016/j.eururo.2009.01.003
Grignon DJ, Che M. Clear cell renal cell carcinoma. Clin Lab Med. 2005;25(2):305–16. DOI: https://doi.org/10.1016/j.cll.2005.01.012
Moch H, Ohashi R. Chromophobe renal cell carcinoma: current and controversial issues. Pathology. 2021;53(1):101–8. DOI: https://doi.org/10.1016/j.pathol.2020.09.015
Kuroda N, Kanomata N, Yamaguchi T, Imamura, et al. Immunohistochemical application of S100A1 in renal oncocytoma, oncocytic papillary renal cell carcinoma, and two variants of chromophobe renal cell carcinoma. Med Mol Morphol. 2011;44(2):111–5. DOI: https://doi.org/10.1007/s00795-009-0461-z
Akgul M, Williamson SR. Immunohistochemistry for the diagnosis of renal epithelial neoplasms. Semin Diagn Pathol. 2022;39(1):1–16. DOI: https://doi.org/10.1053/j.semdp.2021.11.001
Gasparre G, Romeo G, Rugolo M, Porcelli AM. Learning from oncocytic tumors: Why choose inefficient mitochondria? Biochim Biophys Acta. 2011;1807(6):633–42. DOI: https://doi.org/10.1016/j.bbabio.2010.08.006
Leibovich BC, Lohse CM, Crispen PL, et al. Histological subtype is an independent predictor of outcome for patients with renal cell carcinoma. J urol. 2010;183(4):1309–15. DOI: https://doi.org/10.1016/j.juro.2009.12.035
Gakis G, Kramer U, Schilling D, Kruck, et al. Small renal oncocytomas: differentiation with multiphase CT. Eur J Radiol. 2011;80(2):274–8. DOI: https://doi.org/10.1016/j.ejrad.2010.06.049
Zhang X, Dong W, Zhang J, et al. A Novel Mitochondrial-Related Nuclear Gene Signature Predicts Overall Survival of Lung Adenocarcinoma Patients. Front Cell Dev Biol. 2021;9:740487. DOI: https://doi.org/10.3389/fcell.2021.740487
Khialeeva E, Lane TF, Carpenter EM. Disruption of reelin signaling alters mammary gland morphogenesis. Development. 2011;138(4):767–76. DOI: https://doi.org/10.1242/dev.057588
Hou R, Liu X, Yang H, et al. Chemically synthesized cinobufagin suppresses nasopharyngeal carcinoma metastasis by inducing ENKUR to stabilize p53 expression. Cancer Lett. 2022;531:57–70. DOI: https://doi.org/10.1016/j.canlet.2022.01.025
Kocaman N, Artaş G. Can novel adipokines, asprosin and meteorin-like, be biomarkers for malignant mesothelioma? Biotech Histochem. 2020;95(3):171–5. DOI: https://doi.org/10.1080/10520295.2019.1656344
Pan CC, Chen PC, Chiang H. Overexpression of KIT (CD117) in chromophobe renal cell carcinoma and renal oncocytoma. Am J Clin Pathol. 2004;121(6):878–83. DOI: https://doi.org/10.1309/A7M2XTMJQK0KPQER
Yu YC, Han JM, Kim S. Aminoacyl-tRNA synthetases and amino acid signaling. Biochim Biophys Acta Mol Cell Res. 2021;1868(1):118889. DOI: https://doi.org/10.1016/j.bbamcr.2020.118889
Van Berge L, Hamilton EM, Linnankivi T, et al. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: clinical and genetic characterization and target for therapy. Brain. 2014;137(4):1019–29. DOI: https://doi.org/10.1093/brain/awu026
Guo C, Shao T, Jiang X, et al. Comprehensive analysis of the functions and prognostic significance of RNA-binding proteins in bladder urothelial carcinoma. Am J Transl Res. 2020; 12(11):7160–73. DOI: https://doi.org/10.21203/rs.3.rs-44292/v1
Wang J, Zhao X, Wang Y, et al. circRNA-002178 act as a ceRNA to promote PDL1/PD1 expression in lung adenocarcinoma. Cell Death Dis. 2020;11(1):32. DOI: https://doi.org/10.1038/s41419-020-2230-9
Ucer O, Kocaman N. New candidates in the differential diagnosis of malignant mesothelioma from benign mesothelial hyperplasia and adenocarcinoma; DARS2 and suprabasin. Tissue & cell. 2022;79:101920. DOI: https://doi.org/10.1016/j.tice.2022.101920
Chen F, Wang Q, Zhou Y. The construction and validation of an RNA binding protein-related prognostic model for bladder cancer. BMC cancer. 2021;21(1):244. DOI: https://doi.org/10.1186/s12885-021-07930-5
Casuscelli J, Weinhold N, Gundem G, Wang Let al. Genomic landscape and evolution of metastatic chromophobe renal cell carcinoma. JCI insight. 2017;2(12):92688. DOI: https://doi.org/10.1172/jci.insight.92688
Gabriella DA. Reelin in the Years: Controlling Neuronal Migration and Maturation in the Mammalian Brain Hunting. Neurosci. 2014;2014:1–19. DOI: https://doi.org/10.1155/2014/597395
Khialeeva E, Carpenter EM. Non-neuronal roles for the reelin signaling pathway. Dev Dyn. 2017;246(4):217–26. DOI: https://doi.org/10.1002/dvdy.24462
Stein T, Cosimo E, Yu X, et al. Loss of reelin expression in breast cancer is epigenetically controlled and associated with poor prognosis. Am J Pathol. 2010;177(5):2323–33. DOI: https://doi.org/10.2353/ajpath.2010.100209
Sutton KA, Jungnickel MK, Wang Y, et al. Enkurin is a novel calmodulin and TRPC channel binding protein in sperm. Dev Biol. 2004;274(2):426–35. DOI: https://doi.org/10.1016/j.ydbio.2004.07.031
Ma Q, Lu Y, Gu Y. ENKUR Is Involved in the Regulation of Cellular Biology in Colorectal Cancer Cells via PI3K/Akt Signaling Pathway. Technol Cancer Res Treat. 2019;18:1533033819841433. DOI: https://doi.org/10.1177/1533033819841433
Ma Q, Lu Y, Lin J, et al. ENKUR acts as a tumor suppressor in lung adenocarcinoma cells through PI3K/Akt and MAPK/ERK signaling pathways. J Cancer. 2019;10(17):3975–84. DOI: https://doi.org/10.7150/jca.30021
Song T, Zhou P, Sun C, et al. Enkurin domain containing 1 (ENKD1) regulates the proliferation, migration and invasion of non-small cell lung cancer cells. Asia Pac J Clin Oncol. 2022;18(2):39–45. DOI: https://doi.org/10.1111/ajco.13550
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