Molecular biological predictors for kidney cancer

Vtorushin S.V.; Tarakanova V.O.; Zav'jalova M.V.

doi:https://doi.org/10.17116/patol201678156-61

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Abstract:

The paper considers the data available in the modern literature on studies of potential molecular predictors for renal cell carcinoma (RCC). Investigations of cell death markers, namely: Bcl-2 as an inhibitor of apoptosis, are of interest. Its high expression correlates with a more favorable prognosis. Inactivation of Beclin 1 that is an authophagy indicator in intact tissues gives rise to a high risk for tumorigenesis. At the same time, high Beclin 1 expression in the tissue of the tumor itself results in the lower efficiency of performed chemotherapy. Excess annexin A2 in the tumor promotes the growth and invasion of cancer cells. Patients with tumor over-expression of SAM68 protein involved in cell proliferation have a lower overall survival rate. The lifespan of patients without distinct metastases survive significantly longer in the overexpression of epithelial cell adhesion molecule (EpCAM). High PD-L1 protein expression on the cell membrane is considered to be a potential marker of effective immunotherapy for RCC.

Keywords:

kidney cancer

predictors

molecular biological markers

Authors:

Vtorushin S.V.

Tomsk Cancer Research Institute;
Siberian State Medical University, Ministry of Health of Russia, Tomsk, Russia

Tarakanova V.O.

Siberian State Medical University, Ministry of Health of Russia, Tomsk, Russia

Zav'jalova M.V.

FGBU «NII onkologii» SO RAMN, Tomsk

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References:

Zlokachestvennye novoobrazovaniya v Rossii v 2008 g. (zabolevaemost' i smertnost'). Pod red. Chissova V.I., Starinskogo V.V., Petrovoi G.V. M.: FGU «MNIOI im. P.A. Gertsena Rosmedtekhnologii»; 2010.
Lam JS, Shvarts O, Leppert JT, Figlin RA, Belldegrun AS. Renal cell carcinoma 2005: new frontiers in staging, prognostication and targeted molecular therapy. J Urol. 2005;173(6):1853-1862. doi:10.1097/01.ju.0000165693.68449.c3.
Kallio JP, Hirvikoski P, Helin H, Luukkaala T, Tammela TL, Kellokumpu-Lehtinen P, Martikainen PM. Renal cell carcinoma MIB-1, Bax and Bcl-2 expression and prognosis. J Urol. 2004;172(6, Pt 1):2158-2161. doi:10.1097/01.ju.0000144334.97639.bf.
Itoi T, Yamana K, Bilim V, Takahashi K, Tomita F. Impact of frequent Bcl-2 expression on better prognosis in renal cell carcinoma patients. Br J Cancer. 2004;90(1):200-205. doi:10.1038/sj.bjc.6601454
Samaras V, Tsopanomichalou M, Stamatelli A, Arnaoutoglou C, Samaras E, Arnaoutoglou M, Poulias H, Barbatis C. Is there any potential link among caspase-8, p-p38 MAPK and bcl2 in clear cell renal cell carcinomas? Acomparative immunohistochemical analysis with clinical connotations. Diagn Pathol. 2009;4:7. doi:10.1186/1746-1596-4-7.
Miyake H, Sakai I, Muramaki M, Kurahashi T, Takenaka A, Fujisawa M. Prediction of response to combined immunotherapy with interferon-alpha and low-dose interleukin-2 in metastaticrenal cell carcinoma: expression patterns of potential molecular markers in radical nephrectomy specimens. Int J Urol. 2009;16(5):465-471. doi:10.1111/j.1442-2042.2009.02289.x.
Xia S, Lv J, Gao Q, Li L, Chen N, Wei X, Xiao J, Chen J, Tao J, Sun M, Mao C, Zhang L, Xu Z. Prenatal exposure to hypoxia induced beclin 1 signaling-mediated renal autophagy and altered renal development in rat fetuses. Reprod Sci. 2015;22(2):156-164. doi:10.1177/1933719114536474.
Farrugia G, Balzan R. Oxidative stress and programmed cell death in yeast. Front Oncol. 2012;2:64. doi:10.3389/fonc.2012.00064.
Hartleben B, Gödel M, Meyer-Schwesinger C, Liu S, Ulrich T, Köbler S, Wiech T, Grahammer F, Arnold SJ, Lindenmeyer MT, Cohen CD, Pavenstädt H, Kerjaschki D, Mizushima N, Shaw AS, Walz G, Huber TB. Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. J Clin Invest. 2010;120(4):1084-1096. doi:10.1172/jci39492.
Hasima N, Ozpolat B. Regulation of autophagy by polyphenolic compounds as a potential therapeutic strategy for cancer. Cell Death Dis. 2014;5:e1509. doi:10.1038/cddis.2014.467.
Kume S, Uzu T, Horiike K, Chin-Kanasaki M, Isshiki K, Araki S, Sugimoto T, Haneda M, Kashiwagi A, Koya D. Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney. J Clin Invest. 2010;120(4):1043-1055. doi:10.1172/jci41376.
Sato S, Yanagihara T, Ghazizadeh M, Ishizaki M, Adachi A, Sasaki Y, Igarashi T, Fukunaga Y. Correlation of autophagy type in podocytes with histopathological diagnosis of IgA nephropathy. Pathobiology. 2009;76(5):221-226. doi:10.1159/000228897.
Tasdemir E, Galluzzi L, Maiuri MC, Criollo A, Vitale I, Hangen E, Modjtahedi N, Kroemer G. Methods for assessing autophagy and autophagic cell death. Methods Mol Biol. 2008;445:29-76. doi:10.1007/978-1-59745-157-4_3.
Rubinsztein DC. Cdks regulate autophagy via Vps34. Mol Cell. 2010;38(4):483-484. doi:10.1016/j.molcel.2010.05.013.
Pattingre S, Levine B. Bcl-2 inhibition of autophagy: a new route to cancer? Cancer Res. 2006;66(6):2885-2888. doi:10.1158/0008-5472.can-05-4412.
Deng Q, Wang Z, Wang L, Zhang L, Xiang X, Wang Z, Chong T. Lower mRNA and protein expression levels of LC3 and Beclin1, markers of autophagy, were correlated with progression of renal clear cell carcinoma. Jpn J Clin Oncol. 2013;43(12):1261-1268. doi:10.1093/jjco/hyt160.
Pallet N, Bouvier N, Legendre C, Gilleron J, Codogno P, Beaune P, Thervet E, Anglicheau D. Autophagy protects renal tubular cells against cyclosporine toxicity. Autophagy. 2008;4(6):783-791. doi:10.4161/auto.6477.
Bao H, Jiang M, Zhu M, Sheng F, Ruan J, Ruan C. Overexpression of Annexin II affects the proliferation, apoptosis, invasion and production of proangiogenic factors in multiple myeloma. Int J Hematol. 2009;90(2):177-185. doi:10.1007/s12185-009-0356-8.
Mussunoor S, Murray GI. The role of annexins in tumour development and progression. J Pathol. 2008;216(2):131-140. doi:10.1002/path.2400.
Sharma M, Ownbey RT, Sharma MC. Breast cancer cell surface annexin II induces cell migration and neoangiogenesis via tPA dependent plasmin generation. Exp Mol Pathol. 2010;88(2):278-286. doi:10.1016/j.yexmp.2010.01.001.
Hayes MJ, Shao D, Bailly M, Moss SE. Regulation of actin dynamics by annexin 2. EMBO J. 2006;25(9):1816-1826. doi:10.1038/sj.emboj.7601078.
Inokuchi J, Narula N, Yee DS, Skarecky DW, Lau A, Ornstein DK, Tyson DR. Annexin A2 positively contributes to the malignant phenotype and secretion of IL-6 in DU145 prostate cancer cells. Int J Cancer. 2009;124(1):68-74. doi:10.1002/ijc.23928.
Lokman NA, Elder AS, Ween MP, Pyragius CE, Hoffmann P, Oehler MK, Ricciardelli C. Annexin A2 is regulated by ovarian cancer-peritoneal cell interactions and promotes metastasis. Oncotarget. 2013;4(8):1199-1211. doi:10.18632/oncotarget.1122.
Zimmermann U, Woenckhaus C, Pietschmann S, Junker H, Maile S, Schultz K, Protzel C, Giebel J. Expression of annexin II in conventional renal cell carcinoma is correlated with Fuhrman grade and clinical outcome. Virchows Arch. 2004;445(4):368-374. doi:10.1007/s00428-004-1103-4.
Ohno Y, Izumi M, Kawamura T, Nishimura T, Mukai K, Tachibana M. Annexin II represents metastatic potential in clear-cell renal cell carcinoma. Br J Cancer. 2009;101(2):287-294. doi:10.1038/sj.bjc.6605128.
Yang SF, Hsu HL, Chao TK, Hsiao CJ, Lin YF, Cheng CW. Annexin A2 in renal cell carcinoma: Expression, function, and prognostic significance. Urol Oncol. 2015;33(1):11-21. doi:10.1016/j.urolonc.2014.08.015.
Chuthapisith S, Bean BE, Cowley G, Eremin JM, Samphao S, Layfield R, Kerr ID, Wiseman J, El-Sheemy M, Sreenivasan T, Eremin O. Annexins in human breast cancer: Possible predictors of pathological response to neoadjuvant chemotherapy. Eur J Cancer. 2009;45(7):1274-1281. doi:10.1016/j.ejca.2008.
Yan X, Yin J, Yao H, Mao N, Yang Y, Pan L. Increased expression of annexin A3 is a mechanism of platinum resistance in ovarian cancer. Cancer Res. 2010;70(4):1616-1624. doi:10.1158/0008-5472.can-09-3215.
Bielli P, Busà R, Paronetto MP, Sette C. The RNA-binding protein Sam68 is a multifunctional player in human cancer. Endocr Relat Cancer. 2011;18(4):91-102. doi:10.1530/erc-11-0041.
Lukong KE, Richard S. Targeting the RNA-binding protein Sam68 as a treatment for cancer? Future Oncol. 2007;3(5):539-544. doi:10.2217/14796694.3.5.539.
Taylor SJ, Resnick RJ, Shalloway D. Sam68 exerts separable effects on cell cycle progression and apoptosis. BMC Cell Biol. 2004;5:5. doi:10.1186/1471-2121-5-5.
Paronetto MP, Cappellari M, Busà R, Pedrotti S, Vitali R, Comstock C, Hyslop T, Knudsen KE, Sette C. Alternative splicing of the cyclin D1 proto-oncogene is regulated by the RNA-binding protein Sam68. Cancer Res. 2010;70(1):229-239. doi:10.1158/0008-5472.can-09-2788.
Lu F, Gladden AB, Diehl JA. An alternatively spliced cyclin D1 isoform, cyclin D1b, is a nuclear oncogene. Cancer Res. 2003;63(21):7056-7061.
Zhang Z, Li J, Zheng H, Yu C, Chen J, Liu Z, Li M, Zeng M, Zhou F, Song L. Expression and cytoplasmic localization of SAM68 is a significant and independent prognostic marker for renalcell carcinoma. Cancer Epidemiol Biomarkers Prev. 2009;18(10):2685-2693. doi:10.1158/1055-9965.epi-09-0097.
Balzar M, Winter MJ, de Boer CJ, Litvinov SV. The biology of the 17-1A antigen (EpCAM). J Mol Med. 1999;77:699-712. doi:10.1007/s001099900038.
Maetzel D, Denzel S, Mack B, Canis M, Went P, Benk M, Kieu C, Papior P, Baeuerle PA, Munz M, Gires O. Nuclear signalling by tumour-associated antigen EpCAM. Nat Cell Biol. 2009;11:162-171. doi:10.1038/ncb1824.
Brunner A, Prelog M, Verdorfer I, Tzankov A, Mikuz G, Ensinger C. EpCAM is predominantly expressed in high grade and advanced stage urothelial carcinoma of the bladder. J Clin Pathol. 2008;61:307-310. doi:10.1136/jcp.2007.049460.
Patriarca C, Macchi RM, Marschner AK, Mellstedt H. Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. Cancer Treat Rev. 2012;38:68-75. doi:10.1016/j.ctrv.2011.04.002.
Went P, Vasei M, Bubendorf L, Terracciano L, Tornillo L, Riede U, Kononen J, Simon R, Sauter G, Baeuerle PA. Frequent high-level expression of immunotherapeutic target Ep-CAM in colon, stomach, prostrate and lung cancers. Br J Cancer. 2006;94:128-135. doi:10.1038/sj.bjc.6602924.
Seligson DB, Pantuck AJ, Liu X, Huang Y, Horvath S, Bui MH, Han KR, Correa AJ, Eeva M, Tze S, Belldegrun AS, Figlin RA. Epithelial cell adhesion molecule (KSA) expression: pathobiology and its role as an independent predictor of survival in renal cell carcinoma. Clin Cancer Res. 2004;10(8):2659-2669. doi:10.1158/1078-0432.
Shvarts O, Seligson D, Lam J, Shi T, Horvath S, Figlin R, Belldegrun A, Pantuck AJ. p53 is an independent predictor of tumor recurrence and progression after nephrectomy in patients with localized renal cell carcinoma. J Urol. 2005;173(3):725-728. doi:10.1097/01.ju.0000152354.08057.2a.
Zimpfer A, Maruschke M, Rehn S, Kundt G, Litzenberger A, Dammert F, Zettl H, Stephan C, Hakenberg OW, Erbersdobler A. Prognostic and diagnostic implications of epithelial cell adhesion/activating molecule (EpCAM) expression in renal tumours: a retrospective clinicopathological study of 948 cases using tissue microarray. BJU Int. 2014;114(2):296-302. doi:10.1111/bju.12487.
Sabo E, Boltenko A, Sova Y, Stein A, Kleinhaus S, Resnick MB. Microscopic analysis and significance of vascular architectural complexity in renal cell carcinoma. Clin Cancer Res. 2001;7(3):533-537.
Gorban' N.A., Karyakin O.B., Popov A.M., Ivanova S.V., Kudaibergenova A.G., Kondrashova L.M., Barkhatov A.E. Rol' morfometricheskikh pokazatelei vnutriopukholevykh mikrososudov i proliferativnoi aktivnosti opukholevykh kletok pri pochechno-kletochnom rake. Onkourologiya. 2012;4:10-14. doi:10.17650/1726-9776-2012-8-4-10-14.
Sato Y, Sonoda H. The vasohibin family: a negative regulatory system of angiogenesis genetically programmed in endothelial cells. Arterioscler Thromb Vasc Biol. 2007;27:37-41. doi:10.1161/01.atv.0000252062.48280.61.
Tamaki K, Moriya T, Sato Y, Ishida T, Maruo Y, Yoshinaga K, Ohuchi N, Sasano H. Vasohibin-1 in human breast carcinoma: a potential negative feedback regulator of angiogenesis. Cancer Sci. 2009;100(1):88-94. doi:10.1111/j.1349-7006.2008.01015.x.
Kitajima T, Toiyama Y, Tanaka K, Saigusa S, Kobayashi M, Inoue Y, Mohri Y, Kusunoki M. Vasohibin-1 increases the malignant potential of colorectal cancer and is a biomarker of poor prognosis. Anticancer Res. 2014;34(10):5321-5329.
Zhang T, Yu TT, Zhang DM, Hou XM, Liu XJ, Zhao D, Shan L. Vasohibin-1 expression detected by immunohistochemistry correlates with prognosis in non-small cell lung cancer. Med Oncol. 2014;31(5):963. doi:10.1007/s12032-014-0963-y.
Kanomata N, Sato Y, Miyaji Y, Nagai A, Moriya T. Vasohibin-1 is a new predictor of disease-free survival in operated patients with renal cell carcinoma. J Clin Pathol. 2013;66(7):613-619. doi:10.1136/jclinpath-2013-201444.
Wayne K. PD-L1 Expression independent prognostic indicator in mRCC. OncLive. Available at: http://www.onclive.com/conference-coverage/gu-2014/PD-L1-Expression-is-Independent-Prognostic-Indicator-in-Treated-mRCC#sthash.mWn1fnxP.dpuf.