Insulin Receptor Expression in Clear Cell Renal Cell Carcinoma and Its Relation to Prognosis
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose: Both insulin and insulin-like growth factor (IGF)-1 signaling are key regulators of energy metabolism, cellular growth, proliferation, and survival. The IGF-1 receptor (IGF-1R) is overexpressed in most types of human cancers includingrenal cell carcinoma (RCC) with poor prognosis. Insulin receptor (IR) shares downstream effectors with IGF-1R; however, the expression and function of IR in the tumorigenesis of renal cancer remains elusive. Therefore, we examined the expressionof IR and its prognostic significance in clear cell RCC (CCRCC). Materialsand Methods: Immunohistochemical staining for IR was performed on 126 formalin-fixed paraffin-embedded CCRCC tissue samples. Eight of these cases were utilized for western blot analysis. The results were compared with various clinico-pathologic parameters of CCRCC and patient survival. Results: IR was expressed in the nuclei of CCRCC tumor cells in 109 cases (87.9%). Higher IR expression was significantly correlated with the presence of cystic change, lower Fuhrman nuclear grade, lower pathologic T stage, and lower TNM stage, although it wasn’t significantly related to diabetes status and patient survival. Western blot analyses supported the results of the immunohistochemistry studies. Conclusion: IR expression in CCRCC may be associated with favorable prognostic factors.
Abstract
Purpose: Both insulin and insulin-like growth factor (IGF)-1 signaling are key regulators of energy metabolism, cellular growth, proliferation, and survival. The IGF-1 receptor (IGF-1R) is overexpressed in most types of human cancers includingrenal cell carcinoma (RCC) with poor prognosis. Insulin receptor (IR) shares downstream effectors with IGF-1R; however, the expression and function of IR in the tumorigenesis of renal cancer remains elusive. Therefore, we examined the expressionof IR and its prognostic significance in clear cell RCC (CCRCC). Materialsand Methods: Immunohistochemical staining for IR was performed on 126 formalin-fixed paraffin-embedded CCRCC tissue samples. Eight of these cases were utilized for western blot analysis. The results were compared with various clinico-pathologic parameters of CCRCC and patient survival. Results: IR was expressed in the nuclei of CCRCC tumor cells in 109 cases (87.9%). Higher IR expression was significantly correlated with the presence of cystic change, lower Fuhrman nuclear grade, lower pathologic T stage, and lower TNM stage, although it wasn’t significantly related to diabetes status and patient survival. Western blot analyses supported the results of the immunohistochemistry studies. Conclusion: IR expression in CCRCC may be associated with favorable prognostic factors.
참고문헌 (46)
- Rini BI, "Renal cell carcinoma", Lancet, 373, pp.1119~1132 (2009)
- Patard JJ, "Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience", J Clin Oncol, 23, pp.2763~2771 (2005)
- Janzen NK, "Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease", Urol Clin North Am, 30, pp.843~852 (2003)
- Escudier B, "Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up", Ann Oncol, 23(Suppl 7), pp.vii65~vii71 (2012)
- Yu MC, "Cigarette smoking, obesity, diuretic use, and coffee consumption as risk factors for renal cell carcinoma", J Natl Cancer Inst, 77, pp.351~356 (1986)
- Berry MG, "Marked insulin resistance in diabetes mellitus", Am J Med, 4, pp.923~926 (1948)
- Larsson SC, "Diabetes mellitus and incidence of kidney cancer: a meta-analysis of cohort studies", Diabetologia, 54, pp.1013~1018 (2011)
- Lindblad P, "The role of diabetes mellitus in the aetiology of renal cell cancer", Diabetologia, 42, pp.107~112 (1999)
- El-Serag HB, "The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence", Clin Gastroenterol Hepatol, 4, pp.369~380 (2006)
- Huxley R, "Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies", Br J Cancer, 92, pp.2076~2083 (2005)
- Xu X, "Diabetes mellitus and risk of bladder cancer: a meta-analysis of cohort studies", PLoS One, 8, pp.e58079~ (2013)
- Larsson SC, "Diabetes mellitus and risk of colorectal cancer: a meta-analysis", J Natl Cancer Inst, 97, pp.1679~1687 (2005)
- Larsson SC, "Diabetes mellitus and risk of breast cancer: a meta-analysis", Int J Cancer, 121, pp.856~862 (2007)
- Vallon V, "The proximal tubule in the pathophysiology of the diabetic kidney", Am J Physiol Regul Integr Comp Physiol, 300, pp.R1009~R1022 (2011)
- Stewart CE, "Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors", Physiol Rev, 76, pp.1005~1026 (1996)
- Baxter RC, "Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities", Am J Physiol Endocrinol Metab, 278, pp.E967~E976 (2000)
- Ullrich A, "Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes", Nature, 313, pp.756~761 (1985)
- Taniguchi CM, "Critical nodes in signalling pathways: insights into insulin action", Nat Rev Mol Cell Biol, 7, pp.85~96 (2006)
- Ullrich A, "Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity", EMBO J, 5, pp.2503~2512 (1986)
- LeRoith D, "The insulin-like growth factor system and cancer", Cancer Lett, 195, pp.127~137 (2003)
- Parker AS, "High expression levels of insulin-like growth factor-I receptor predict poor survival among women with clear-cell renal cell carcinomas", Hum Pathol, 33, pp.801~805 (2002)
- Belfiore A, "IGF and insulin receptor signaling in breast cancer", J Mammary Gland Biol Neoplasia, 13, pp.381~406 (2008)
- Beauchamp MC, "Targeting insulin and insulin-like growth factor pathways in epithelial ovarian cancer", J Oncol, 2010, pp.257058~ (2010)
- Edge SB, "AJCC cancer staging manual. 7th ed", pp.479~486 (2010), Springer
- Fuhrman SA, "Prognostic significance of morphologic parameters in renal cell carcinoma", Am J Surg Pathol, 6, pp.655~663 (1982)
- Allred DC, "Prognostic and predictive factors in breast cancer by immunohistochemical analysis", Mod Pathol, 11, pp.155~168 (1998)
- Ahmad N, "The expression of insulin-like growth factor-I receptor correlates with Fuhrman grading of renal cell carcinomas", Hum Pathol, 35, pp.1132~1136 (2004)
- He X, "Regulation of receptor for activated C kinase 1 protein by the von Hippel-Lindau tumor suppressor in IGF-I-induced renal carcinoma cell invasiveness", Oncogene, 30, pp.535~547 (2011)
- Ljungberg B, "EAU guidelines on renal cell carcinoma: the 2010 update", Eur Urol, 58, pp.398~406 (2010)
- 문경철, "The Prognostic Implications of Cystic Change in Clear Cell Renal Cell Carcinoma", Journal of Pathology and Translational Medicine, 44(2), pp.149~154 (2010), 대한병리학회
- Moller DE, "Tissue-specific expression of two alternatively spliced insulin receptor mRNAs in man", Mol Endocrinol, 3, pp.1263~1269 (1989)
- Kern M, "Insulin responsiveness in skeletal muscle is determined by glucose transporter (Glut4) protein level", Biochem J, 270, pp.397~400 (1990)
- Höfner T, "The impact of type 2 diabetes on the outcome of localized renal cell carcinoma", World J Urol (2013)
- Parker A, "Expression of insulin-like growth factor I receptor and survival in patients with clear cell renal cell carcinoma", J Urol, 170(2 Pt 1), pp.420~424 (2003)
- Najjar SM, "Differential phosphorylation of pp120 by insulin and insulin-like growth factor-1 receptors: role for the C-terminal domain of the beta-subunit", Biochemistry, 36, pp.6827~6834 (1997)
- O’Neill TJ, "Interaction of MAD2 with the carboxyl terminus of the insulin receptor but not with the IGFIR. Evidence for release from the insulin receptor after activation", J Biol Chem, 272, pp.10035~10040 (1997)
- Bausch B, "Renal cancer in von Hippel-Lindau disease and related syndromes", Nat Rev Nephrol, 9, pp.529~538 (2013)
- Finley DS, "Tumor biology and prognostic factors in renal cell carcinoma", Oncologist, 16(Suppl 2), pp.4~13 (2011)
- Yim S, "Insulin and hypoxia share common target genes but not the hypoxia-inducible factor-1alpha", J Biol Chem, 278, pp.38260~38268 (2003)
- Aleksic T, "Type 1 insulin-like growth factor receptor translocates to the nucleus of human tumor cells", Cancer Res, 70, pp.6412~6419 (2010)
- Resnik JL, "Elevated insulin-like growth factor I receptor autophosphorylation and kinase activity in human breast cancer", Cancer Res, 58, pp.1159~1164 (1998)
- Cappuzzo F, "Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small-cell lung cancer patients treated with gefitinib", Ann Oncol, 17, pp.1120~1127 (2006)
- Ahlén J, "Insulin-like growth factor type 1 receptor expression correlates to good prognosis in highly malignant soft tissue sarcoma", Clin Cancer Res, 11, pp.206~216 (2005)
- Sehat B, "SUMOylation mediates the nuclear translocation and signaling of the IGF-1 receptor", Sci Signal, 3, pp.ra10~ (2010)
- Amaya MJ, "The insulin receptor translocates to the nucleus to regulate cell proliferation in liver", Hepatology, 59, pp.274~283 (2014)
- Kim JS, "Prognostic impact of insulin receptor expression on survival of patients with nonsmall cell lung cancer", CANCER, 118(9), pp.2454~2465 (2012), WILEY-BLACKWELL
