Abstract
Renal cancer is an aggressive and incurable disease with a worldwide prevalence that ranks it to be twelfth most common type of cancer. According to world cancer statistics, around 338,000 new kidney cancer incidences are diagnosed annually. Renal cancer is caused by various sporadic or familial mutations that lead to the accumulation of genomic aberrations enough to impair cell proliferation and differentiation. Epigenetic factors such as hypermethylation also adds up to the malignancy. Kidney heterogeneity makes it really tough to treat renal cancer since (a) different cells are affected in different types of renal cancer, and (b) diagnosis is very incidental and the symptoms appear only in the advance stages. Kidney cancer can be detected by conventional methods based on tumor morphology and tissue histology, while radical nephrectomy or more recently nephron-sparing surgery is the only treatment available in advance cancer stages. Evolvement of molecular techniques and integration in transcriptomics, proteomics and metabolomics, has lead to the quantification of a wide range of chemical fingerprints left behind by alterations caused by different types of renal cancer at earlier stages. These non-invasive biomarkers has the potential to detect renal cancer before they metastasize, improve cancer diagnosis, prognosis, and provide more personalized and targeted therapies in patient care. In this chapter, we have summarized the various molecular techniques and renal cancer biomarkers available to detect early stages with a possibility to have clinical implications in near future.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ferlay J, Soerjomataram I, Mea E. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11. Lyon: International Agency for Research on Cancer; 2013. p. 1.0.
Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013;132(5):1133–45.
Linehan W, et al. Molecular diagnosis and therapy of kidney cancer. Annu Rev Med. 2010;61:329–43.
Pastore AL, et al. Serum and urine biomarkers for human renal cell carcinoma. Dis Mark. 2015;2015:251403.
Leppert JT, Pantuck AJ, Figlin RA, Belldegrun AS. The role of molecular markers in the staging of renal cell carcinoma. BJU Int. 2007;99(5b):1208–11.
Audenet F, Yates D, Cancel-Tassin G, Cussenot O, Rouprêt M. Genetic pathways involved in carcinogenesis of clear cell renal cell carcinoma: genomics towards personalized medicine. BJU Int. 2012;109:1864–70.
Daniel CR, et al. Large prospective investigation of meat intake, related mutagens, and risk of renal cell carcinoma. Am J Clin Nutr. 2012;95(1):155–62.
T P, et al. Body size and risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition (EPIC). Int J Cancer. 2006;118(3):728–38.
Xu Y, et al. The impact of smoking on survival in renal cell carcinoma: a systematic review and meta-analysis. Tumor Biol. 2014;35(7):6633–40.
Sanfilippo KM, et al. Hypertension and obesity and the risk of kidney cancer in 2 large cohorts of US men and women. Hypertension. 2014;63(5):934–41.
Hu J, et al. Renal cell carcinoma and occupational exposure to chemicals in Canada. Occup Med. 2002;52(3):157–64.
Muglia VF, Prando A. Renal cell carcinoma: histological classification and correlation with imaging findings. Radiol Bras. 2015;48(3):166–74.
Cairns P. Renal cell carcinoma. Cancer Biomark. 2011;9(1–6):461–73.
Sachdeva K. Renal cell carcinoma staging; 2017. https://www.cancer.org/cancer/kidney-cancer/detection-diagnosis-staging/staging.html.
Haase VH. The VHL/HIF oxygen-sensing pathway and its relevance to kidney disease. Kidney Int. 2006;69(8):1302–7.
Organ S, Tsao M. An overview of the c-MET signaling pathway. Ther Adv Med Oncol. 2011;3(1 Suppl):S7–S19.
L S, et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet. 1997;16(1):68–73.
Linehan WM, Srinivasan R, Schmidt LS. The genetic basis of kidney cancer: a metabolic disease. Nat Rev Urol. 2010;5:277.
Linehan WM, Walther MM, Zbar B. The genetic basis of cancer of the kidney. J Urol. 2003;170(6 Part 1):2163.
Menko FH, et al. Hereditary leiomyomatosis and renal cell cancer (HLRCC). Renal cancer risk, surveillance and treatment. Fam Cancer. 2014;13(4):637–44.
Schneider M, et al. Early onset renal cell carcinoma in an adolescent girl with germline FLCN exon 5 deletion. Fam Cancer. 2018;17(1):135–9. Cite as(1):135–9.
Pavlovich C, et al. Renal tumors in the Birt-Hogg-Dubé syndrome. Am J Surg Pathol. 2002;26(12):1542–52.
Ramakrishnan S, Ellis L, Pili R. Histone modifications: implications in renal cell carcinoma. Epigenomics. 2013;5(4):453–62.
Shenoy N, et al. Role of DNA methylation in renal cell carcinoma. J Hematol Oncol. 2015;8:88.
Tunuguntla HS, Jorda M. Diagnostic and prognostic molecular markers in renal cell carcinoma. J Urol. 2008;179(6):2096.
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.
DI Carlo A. Evaluation of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and their complex MMP-9/NGAL in sera and urine of patients with kidney tumors. Oncol Lett. 2013;5(5):1677–81.
Won KH, et al. Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell carcinoma. J Am Soc Nephrol. 2005;16(4):1126–34.
Bonventre J. Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more. Nephrol Dial Transplant. 2009;24(11):3265–8.
Jeremiah JM, Amy NL, Jingqin L, Evan DK. Urinary biomarkers for the early diagnosis of kidney cancer. Mayo Clin Proc. 2010;85(5):413–21.
Rajandram R, et al. Tumour necrosis factor receptor-associated factor-1 (TRAF-1) expression is increased in renal cell carcinoma patient serum but decreased in cancer tissue compared with normal: potential biomarker significance. Pathology. 2014;46(6):518–22.
Bennett NC, et al. Patient samples of renal cell carcinoma show reduced expression of TRAF1 compared with normal kidney and functional studies in vitro indicate TRAF1 promotes apoptosis: potential for targeted therapy. Pathology. 2012;44(5):453–9.
Hofbauer S, et al. Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma. Br J Cancer. 2014;111(8):1526–31.
Ramp U, et al. Apoptosis induction in renal cell carcinoma by TRAIL and γ-radiation is impaired by deficient caspase-9 cleavage. Br J Cancer. 2003;88(11):1800–7.
Déjosez M, et al. Sensitivity to TRAIL/APO-2L-mediated apoptosis in human renal cell carcinomas and its enhancement by topotecan. Cell Death Differ. 2000;7(11):1127–36.
I Y, et al. Serum M65 as a biomarker for metastatic renal cell carcinoma. Clin Genitourin Cancer. 2013;11(3):290–6.
Frew IJ, Moch H. A clearer view of the molecular complexity of clear cell renal cell carcinoma. Annu Rev Pathol Mech Dis. 2015;10(1):263–89.
Tanaka T, Kitamura H, Torigoe T, et al. Autoantibody against hypoxia-inducible factor prolyl hydroxylase-3 is a potential serological marker for renal cell carcinoma. J Cancer Res Clin Oncol. 2011;137(5):789–94.
Takacova M, et al. Carbonic anhydrase IX is a clinically significant tissue and serum biomarker associated with renal cell carcinoma. Oncol Lett. 2013;5(1):191–7.
Silva D, et al. Serum tissue factor as a biomarker for renal clear cell carcinoma. Int Braz J Urol. 2018;44(1):38–44.
Tan W, et al. Role of inflammatory related gene expression in clear cell renal cell carcinoma development and clinical outcomes. J Urol. 2011;186(5):2071–7.
Iqbal MA, Akhtar M, Al Dayel F, Ulmer C, Paterson MC. Use of fish analysis for diagnosis of renal cell carcinoma subtypes. Ann Saudi Med. 1999;19(6):495–500.
Kim S, et al. Usefulness of a break-apart FISH assay in the diagnosis of Xp11.2 translocation renal cell carcinoma. Virchows Arch. 2011;459(3):299–306.
Pradhan D, et al. Validation and utilization of a TFE3 break-apart FISH assay for Xp11.2 translocation renal cell carcinoma and alveolar soft part sarcoma. Diagn Pathol. 2015;10(1):179.
Pflueger D, et al. Identification of molecular tumor markers in renal cell carcinomas with TFE3 protein expression by RNA sequencing. Neoplasia. 2013;15(11):1231–40.
Hahn AW, et al. Correlation of genomic alterations assessed by next-generation sequencing (NGS) of tumor tissue DNA and circulating tumor DNA (ctDNA) in metastatic renal cell carcinoma (mRCC): potential clinical implications. Oncotarget. 2017;8(20):33614–20.
Di Napoli A, Signoretti S. Tissue biomarkers in renal cell carcinoma: issues and solutions. Cancer. 2009;115(10 Suppl):2290–7.
Barr ML, et al. PAX-8 expression in renal tumours and distant sites: a useful marker of primary and metastatic renal cell carcinoma? J Clin Pathol. 2014;68(1):12–7.
Knoepp S, Kunju LP, Roh MH. Utility of PAX8 and PAX2 immunohistochemistry in the identification of renal cell carcinoma in diagnostic cytology. Diagn Cytopathol. 2012;40(8):667–72.
Miettinen M, Lasota J. KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol. 2005;13(3):205–20.
Ahmed EA, Youssif ME. Immunohistochemical study of c-KIT (CD117) expression in renal cell carcinoma. J Egypt Natl Canc Inst. 2009;21(2):121–32.
Martignoni G, et al. Validation of 34betaE12 immunoexpression in clear cell papillary renal cell carcinoma as a sensitive biomarker. Pathology. 2017;49(1):10–8.
Farber N, et al. Renal cell carcinoma: the search for a reliable biomarker. Transl Cancer Res. 2017;6(3):620–32.
Slade L, Pulinilkunnil T. The MiTF/TFE family of transcription factors: master regulators of organelle signaling, metabolism, and stress adaptation. Mol Cancer Res. 2017 15(12):1637–43.
Alshenawy HA. Immunohistochemical panel for differentiating renal cell carcinoma with clear and papillary features. Pathol Oncol Res. 2015;21(4):893–9.
Lee HJ, et al. Combination of immunohistochemistry, FISH and RT-PCR shows high incidence of Xp11 translocation RCC: comparison of three different diagnostic methods. Oncotarget. 2017;8(19):30756–65.
Kim K, et al. Urine metabolomics analysis for kidney cancer detection and biomarker discovery. Mol Cell Proteomics. 2009;8(3):558–70.
Kind T, Tolstikov V, Fiehn O, Weiss R. A comprehensive urinary metabolomic approach for identifying kidney cancer. Anal Biochem. 2007;363(2):185–95.
Rogers M, et al. Proteomic profiling of urinary proteins in renal cancer by surface enhanced laser desorption ionization and neural-network analysis. Cancer Res. 2003;63(20):6971–83.
Fischer K, Theil G, Hoda R, Fornara P. Serum amyloid a: a biomarker for renal cancer. Anticancer Res. 2012;32(5):1801–4.
Wulfken L, et al. MicroRNAs in renal cell carcinoma: diagnostic implications of serum miR-1233 levels. PLoS One. 2011;6(9):e25787.
Wang C, et al. A panel of five serum miRNAs as a potential diagnostic tool for early-stage renal cell carcinoma. Sci Rep. 2015;5(1):7610.
Li M, et al. MicroRNAs in renal cell carcinoma: a systematic review of clinical implications (review). Oncol Rep. 2015;33(4):1571–8.
Li M, Wang Y, Cheng L, Niu W, Zhao G, Raju JK, et al. Long non-coding RNAs in renal cell carcinoma: a systematic review and clinical implications. Oncotarget. 2017;8(29):48424–35.
Yu G, et al. LncRNAs expression signatures of renal clear cell carcinoma revealed by microarray. PLoS One. 2012;7(8):e42377.
Ellinger J, et al. The long non-coding RNA lnc-ZNF180–2 is a prognostic biomarker in patients with clear cell renal cell carcinoma. Am J Cancer Res. 2015;5(9):2799–807.
Ball MW, et al. Circulating tumor DNA as a marker of therapeutic response in patients with renal cell carcinoma: a pilot study. Clin Genitourin Cancer. 2016;14(5):e515–20.
Cohen RJ. Pathology of clear cell renal cell carcinoma; 2016. https://emedicine.medscape.com/article/1612043-overview.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Sanganeria, B.S., Misra, R., Shukla, K.K. (2019). Molecular Diagnostics in Renal Cancer. In: Shukla, K., Sharma, P., Misra, S. (eds) Molecular Diagnostics in Cancer Patients. Springer, Singapore. https://doi.org/10.1007/978-981-13-5877-7_13
Download citation
DOI: https://doi.org/10.1007/978-981-13-5877-7_13
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-5876-0
Online ISBN: 978-981-13-5877-7
eBook Packages: MedicineMedicine (R0)