Skip to main content
Erschienen in: Tumor Biology 2/2016

09.09.2015 | Original Article

The clinical and biological significance of MICA in clear cell renal cell carcinoma patients

verfasst von: Xiang Zhang, Lei Yan, Wei Jiao, Juchao Ren, Naidong Xing, Yongzhen Zhang, Yuanwei Zang, Jue Wang, Zhonghua Xu

Erschienen in: Tumor Biology | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

Abstract

Major histocompatibility complex class I-related chains A (MICA), a ligand of Natural killer group 2, member D (NKG2D) receptor, is broadly upregulated in epithelial originated tumor cells. MICA plays a critical role in the immune surveillance against tumor cells and is associated with the prognosis of several malignancies. The aim of this study is to evaluate the clinical and biological significance of MICA in clear cell renal cell carcinoma (ccRCC). The expression of MICA was analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Both MICA mRNA and protein levels were upregulated in ccRCC tissues, compared with normal tissues. IHC staining revealed a homogenous pattern of MICA staining within each tumor, which combined both membrane staining and granular cytoplasmic staining. Furthermore, high MICA expression was associated with lymph node metastasis and advanced clinical stage and predicted poor prognosis in patients with ccRCC. Gene set enrichment analysis (GSEA) was performed using RNA-sequencing data from The Cancer Genome Atlas Research Network (TCGA) to elucidate the biological role of MICA in ccRCC and revealed that MICA was significantly associated with the epithelial-to-mesenchymal transition (EMT) gene set, which was further confirmed by qRT-PCR. Our findings contribute to the studies on biomarkers of kidney cancers and the mechanism of renal cancer progression driven by EMT pathway.
Literatur
1.
Zurück zum Zitat Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.CrossRefPubMed Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.CrossRefPubMed
2.
Zurück zum Zitat Janzen NK, Kim HL, Figlin RA, Belldegrun AS. Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin N Am. 2003;30:843–52.CrossRef Janzen NK, Kim HL, Figlin RA, Belldegrun AS. Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin N Am. 2003;30:843–52.CrossRef
3.
Zurück zum Zitat Eisengart LJ, MacVicar GR, Yang XJ. Predictors of response to targeted therapy in renal cell carcinoma. Arch Pathol Lab Med. 2012;136:490–5.CrossRefPubMed Eisengart LJ, MacVicar GR, Yang XJ. Predictors of response to targeted therapy in renal cell carcinoma. Arch Pathol Lab Med. 2012;136:490–5.CrossRefPubMed
4.
Zurück zum Zitat Groh V, Steinle A, Bauer S, Spies T. Recognition of stress-induced mhc molecules by intestinal epithelial gammadelta t cells. Science. 1998;279:1737–40.CrossRefPubMed Groh V, Steinle A, Bauer S, Spies T. Recognition of stress-induced mhc molecules by intestinal epithelial gammadelta t cells. Science. 1998;279:1737–40.CrossRefPubMed
5.
Zurück zum Zitat Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, et al. Activation of nk cells and t cells by nkg2d, a receptor for stress-inducible mica. Science. 1999;285:727–9.CrossRefPubMed Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, et al. Activation of nk cells and t cells by nkg2d, a receptor for stress-inducible mica. Science. 1999;285:727–9.CrossRefPubMed
6.
Zurück zum Zitat Salih HR, Antropius H, Gieseke F, Lutz SZ, Kanz L, Rammensee HG, et al. Functional expression and release of ligands for the activating immunoreceptor nkg2d in leukemia. Blood. 2003;102:1389–96.CrossRefPubMed Salih HR, Antropius H, Gieseke F, Lutz SZ, Kanz L, Rammensee HG, et al. Functional expression and release of ligands for the activating immunoreceptor nkg2d in leukemia. Blood. 2003;102:1389–96.CrossRefPubMed
7.
Zurück zum Zitat Watson NF, Spendlove I, Madjd Z, McGilvray R, Green AR, Ellis IO, et al. Expression of the stress-related mhc class i chain-related protein mica is an indicator of good prognosis in colorectal cancer patients. Int J Cancer J Int Cancer. 2006;118:1445–52.CrossRef Watson NF, Spendlove I, Madjd Z, McGilvray R, Green AR, Ellis IO, et al. Expression of the stress-related mhc class i chain-related protein mica is an indicator of good prognosis in colorectal cancer patients. Int J Cancer J Int Cancer. 2006;118:1445–52.CrossRef
8.
Zurück zum Zitat Chen Y, Lin G, Guo ZQ, Zhou ZF, He ZY, Ye YB. Effects of mica expression on the prognosis of advanced non-small cell lung cancer and the efficacy of cik therapy. PLoS ONE. 2013;8:e69044.CrossRefPubMedPubMedCentral Chen Y, Lin G, Guo ZQ, Zhou ZF, He ZY, Ye YB. Effects of mica expression on the prognosis of advanced non-small cell lung cancer and the efficacy of cik therapy. PLoS ONE. 2013;8:e69044.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Wu J, Zhang XJ, Shi KQ, Chen YP, Ren YF, Song YJ, et al. Hepatitis b surface antigen inhibits mica and micb expression via induction of cellular mirnas in hepatocellular carcinoma cells. Carcinogenesis. 2014;35:155–63.CrossRefPubMed Wu J, Zhang XJ, Shi KQ, Chen YP, Ren YF, Song YJ, et al. Hepatitis b surface antigen inhibits mica and micb expression via induction of cellular mirnas in hepatocellular carcinoma cells. Carcinogenesis. 2014;35:155–63.CrossRefPubMed
10.
Zurück zum Zitat Li JJ, Pan K, Gu MF, Chen MS, Zhao JJ, Wang H, et al. Prognostic value of soluble mica levels in the serum of patients with advanced hepatocellular carcinoma. Chin J Cancer. 2013;32:141–8.CrossRefPubMedPubMedCentral Li JJ, Pan K, Gu MF, Chen MS, Zhao JJ, Wang H, et al. Prognostic value of soluble mica levels in the serum of patients with advanced hepatocellular carcinoma. Chin J Cancer. 2013;32:141–8.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Kumar V, Yi Lo PH, Sawai H, Kato N, Takahashi A, Deng Z, et al. Soluble mica and a mica variation as possible prognostic biomarkers for hbv-induced hepatocellular carcinoma. PLoS ONE. 2012;7:e44743.CrossRefPubMedPubMedCentral Kumar V, Yi Lo PH, Sawai H, Kato N, Takahashi A, Deng Z, et al. Soluble mica and a mica variation as possible prognostic biomarkers for hbv-induced hepatocellular carcinoma. PLoS ONE. 2012;7:e44743.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Zhang J, Xu Z, Zhou X, Zhang H, Yang N, Wu Y, et al. Loss of expression of mhc class i-related chain a (mica) is a frequent event and predicts poor survival in patients with hepatocellular carcinoma. Int J Clin Exp Pathol. 2014;7:3123–31.PubMedPubMedCentral Zhang J, Xu Z, Zhou X, Zhang H, Yang N, Wu Y, et al. Loss of expression of mhc class i-related chain a (mica) is a frequent event and predicts poor survival in patients with hepatocellular carcinoma. Int J Clin Exp Pathol. 2014;7:3123–31.PubMedPubMedCentral
13.
Zurück zum Zitat Madjd Z, Spendlove I, Moss R, Bevin S, Pinder SE, Watson NF, et al. Upregulation of mica on high-grade invasive operable breast carcinoma. Cancer Immun. 2007;7:17.PubMedPubMedCentral Madjd Z, Spendlove I, Moss R, Bevin S, Pinder SE, Watson NF, et al. Upregulation of mica on high-grade invasive operable breast carcinoma. Cancer Immun. 2007;7:17.PubMedPubMedCentral
14.
Zurück zum Zitat Tamaki S, Sanefuzi N, Kawakami M, Aoki K, Imai Y, Yamanaka Y, et al. Association between soluble mica levels and disease stage iv oral squamous cell carcinoma in japanese patients. Hum Immunol. 2008;69:88–93.CrossRefPubMed Tamaki S, Sanefuzi N, Kawakami M, Aoki K, Imai Y, Yamanaka Y, et al. Association between soluble mica levels and disease stage iv oral squamous cell carcinoma in japanese patients. Hum Immunol. 2008;69:88–93.CrossRefPubMed
15.
Zurück zum Zitat Eble J, Sauter G, Epstein J, Sesterhenn IE. World health organization classification of tumors pathology and genetics of the urinary systemandmale genital organs. Lyon: LARC Press; 2004. p. 12–4. Eble J, Sauter G, Epstein J, Sesterhenn IE. World health organization classification of tumors pathology and genetics of the urinary systemandmale genital organs. Lyon: LARC Press; 2004. p. 12–4.
16.
Zurück zum Zitat Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982;6:655–63.CrossRefPubMed Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982;6:655–63.CrossRefPubMed
17.
Zurück zum Zitat Lee J, Jeong S, Lee CR, Ku CR, Kang SW, Jeong JJ, et al. Gli1 transcription factor affects tumor aggressiveness in patients with papillary thyroid cancers. Medicine. 2015;94:e998.CrossRefPubMedPubMedCentral Lee J, Jeong S, Lee CR, Ku CR, Kang SW, Jeong JJ, et al. Gli1 transcription factor affects tumor aggressiveness in patients with papillary thyroid cancers. Medicine. 2015;94:e998.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Lopez-Soto A, Huergo-Zapico L, Galvan JA, Rodrigo L, de Herreros AG, Astudillo A, et al. Epithelial-mesenchymal transition induces an antitumor immune response mediated by nkg2d receptor. J Immunol. 2013;190:4408–19.CrossRefPubMed Lopez-Soto A, Huergo-Zapico L, Galvan JA, Rodrigo L, de Herreros AG, Astudillo A, et al. Epithelial-mesenchymal transition induces an antitumor immune response mediated by nkg2d receptor. J Immunol. 2013;190:4408–19.CrossRefPubMed
19.
Zurück zum Zitat Jia HY, Liu JL, Zhou CJ, Kong F, Yuan MZ, Sun WD, et al. High expression of mica in human kidney cancer tissue and renal cell carcinoma lines. Asian Pac J Cancer Prev : APJCP. 2014;15:1715–7.CrossRefPubMed Jia HY, Liu JL, Zhou CJ, Kong F, Yuan MZ, Sun WD, et al. High expression of mica in human kidney cancer tissue and renal cell carcinoma lines. Asian Pac J Cancer Prev : APJCP. 2014;15:1715–7.CrossRefPubMed
20.
Zurück zum Zitat Roberts AI, Lee L, Schwarz E, Groh V, Spies T, Ebert EC, et al. Nkg2d receptors induced by il-15 costimulate cd28-negative effector ctl in the tissue microenvironment. J Immunol. 2001;167:5527–30.CrossRefPubMed Roberts AI, Lee L, Schwarz E, Groh V, Spies T, Ebert EC, et al. Nkg2d receptors induced by il-15 costimulate cd28-negative effector ctl in the tissue microenvironment. J Immunol. 2001;167:5527–30.CrossRefPubMed
21.
Zurück zum Zitat Xiao P, Xue L, Che LH, Peng JJ, Wu HX, Li Y, et al. Expression and roles of mica in human osteosarcoma. Histopathology. 2008;52:640–2.CrossRefPubMed Xiao P, Xue L, Che LH, Peng JJ, Wu HX, Li Y, et al. Expression and roles of mica in human osteosarcoma. Histopathology. 2008;52:640–2.CrossRefPubMed
22.
Zurück zum Zitat Li K, Mandai M, Hamanishi J, Matsumura N, Suzuki A, Yagi H, et al. Clinical significance of the nkg2d ligands, mica/b and ulbp2 in ovarian cancer: High expression of ulbp2 is an indicator of poor prognosis. Cancer Immunol Immunother. 2009;58:641–52.CrossRefPubMed Li K, Mandai M, Hamanishi J, Matsumura N, Suzuki A, Yagi H, et al. Clinical significance of the nkg2d ligands, mica/b and ulbp2 in ovarian cancer: High expression of ulbp2 is an indicator of poor prognosis. Cancer Immunol Immunother. 2009;58:641–52.CrossRefPubMed
23.
Zurück zum Zitat Groh V, Wu J, Yee C, Spies T. Tumour-derived soluble mic ligands impair expression of nkg2d and t-cell activation. Nature. 2002;419:734–8.CrossRefPubMed Groh V, Wu J, Yee C, Spies T. Tumour-derived soluble mic ligands impair expression of nkg2d and t-cell activation. Nature. 2002;419:734–8.CrossRefPubMed
24.
Zurück zum Zitat Salih HR, Rammensee HG, Steinle A. Cutting edge: Down-regulation of mica on human tumors by proteolytic shedding. J Immunol. 2002;169:4098–102.CrossRefPubMed Salih HR, Rammensee HG, Steinle A. Cutting edge: Down-regulation of mica on human tumors by proteolytic shedding. J Immunol. 2002;169:4098–102.CrossRefPubMed
25.
Zurück zum Zitat Sconocchia G, Spagnoli GC, Del Principe D, Ferrone S, Anselmi M, Wongsena W, et al. Defective infiltration of natural killer cells in mica/b-positive renal cell carcinoma involves beta(2)-integrin-mediated interaction. Neoplasia. 2009;11:662–71.CrossRefPubMedPubMedCentral Sconocchia G, Spagnoli GC, Del Principe D, Ferrone S, Anselmi M, Wongsena W, et al. Defective infiltration of natural killer cells in mica/b-positive renal cell carcinoma involves beta(2)-integrin-mediated interaction. Neoplasia. 2009;11:662–71.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Sconocchia G, Arriga R, Tornillo L, Terracciano L, Ferrone S, Spagnoli GC. Melanoma cells inhibit nk cell functions. Cancer Res. 2012;72:5428–9. author reply 5430.CrossRefPubMed Sconocchia G, Arriga R, Tornillo L, Terracciano L, Ferrone S, Spagnoli GC. Melanoma cells inhibit nk cell functions. Cancer Res. 2012;72:5428–9. author reply 5430.CrossRefPubMed
27.
Zurück zum Zitat Boissel N, Rea D, Tieng V, Dulphy N, Brun M, Cayuela JM, et al. Bcr/abl oncogene directly controls mhc class i chain-related molecule a expression in chronic myelogenous leukemia. J Immunol. 2006;176:5108–16.CrossRefPubMed Boissel N, Rea D, Tieng V, Dulphy N, Brun M, Cayuela JM, et al. Bcr/abl oncogene directly controls mhc class i chain-related molecule a expression in chronic myelogenous leukemia. J Immunol. 2006;176:5108–16.CrossRefPubMed
Metadaten
Titel
The clinical and biological significance of MICA in clear cell renal cell carcinoma patients
verfasst von
Xiang Zhang
Lei Yan
Wei Jiao
Juchao Ren
Naidong Xing
Yongzhen Zhang
Yuanwei Zang
Jue Wang
Zhonghua Xu
Publikationsdatum
09.09.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4041-7

Weitere Artikel der Ausgabe 2/2016

Tumor Biology 2/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.