Tumor Biology

, Volume 34, Issue 6, pp 3431–3435 | Cite as

Evaluating the expression of CARMA3 as a prognostic tumor marker in renal cell carcinoma

  • Guang-Li Wu
  • Jian-Lin Yuan
  • Xu-Dong Huang
  • Jun-Fang Rong
  • Li-Xia Zhang
  • Yue-Ping Liu
  • Fu-Li Wang
Research Article


Increased expression of CARMA3 has been reported to be involved in tumorigenesis and tumor progression of several cancer types. The aim of our study is to investigate the prognostic role of CARMA3 expression in patients with renal cell carcinoma (RCC). Real-time quantitative PCR was performed to detect CARMA3 mRNA expression level in 31 paired samples of RCC and adjacent noncancerous renal tissues. Subsequently, extensive immunohistochemistry was performed to detect CARMA3 protein expression in 114 RCC cases. Clinicopathological data for these patients were evaluated. The prognostic significance was assessed using the Kaplan–Meier survival estimates and log-rank tests. CARMA3 mRNA expression was significantly higher in RCC tissues compared with adjacent noncancerous renal tissues (3.525 ± 1.233 vs. 1.512 ± 0.784, P < 0.001). In addition, high CARMA3 expression in RCC tissues was significantly associated with tumor size (P = 0.026), histological differentiation (P = 0.039), tumor stage (P = 0.006), and the presence of metastasis (P < 0.001). Moreover, Kaplan–Meier analysis showed that patients with high CARMA3 expression also had a significantly poorer prognosis than those with low CARMA3 expression (log-rank test, P < 0.001). Furthermore, multivariate analysis illustrated that CARMA3 overexpression might be an independent prognostic indicator for the survival of patients with RCC. In conclusion, this work shows that CARMA3 may serve as a novel and prognostic marker for RCC and play a role during the development and progression of the disease.


CARMA3 Renal cell carcinoma Prognosis 


Conflicts of interest



  1. 1.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300. doi: 10.3322/caac.20073.PubMedCrossRefGoogle Scholar
  2. 2.
    Tolia BM, Whitmore Jr WF. Solitary metastasis from renal cell carcinoma. J Urol. 1975;114:836–8.PubMedGoogle Scholar
  3. 3.
    Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C. Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev. 2008;34:193–205. doi: 10.1016/j.ctrv.2007.12.001.PubMedCrossRefGoogle Scholar
  4. 4.
    Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med. 2005;353(23):2477–90. doi: 10.1056/NEJMra043172.PubMedCrossRefGoogle Scholar
  5. 5.
    Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27:3584–90. doi: 10.1200/JCO.2008.20.1293.PubMedCrossRefGoogle Scholar
  6. 6.
    Stilo R, Liguoro D, Di Jeso B, Formisano S, Consiglio E, Leonardi A, et al. Physical and functional interaction of CARMA1 and CARMA3 with Ikappa kinase gamma-NFkappaB essential modulator. J Biol Chem. 2004;279:34323–31. doi: 10.1074/jbc.M402244200.PubMedCrossRefGoogle Scholar
  7. 7.
    Grabiner BC, Blonska M, Lin PC, You Y, Wang D, Sun J, et al. CARMA3 deficiency abrogates G protein-coupled receptor-induced NF-{kappa}B activation. Genes Dev. 2007;21:984–96. doi: 10.1101/gad.1502507.PubMedCrossRefGoogle Scholar
  8. 8.
    McAllister-Lucas LM, Ruland J, Siu K, Jin X, Gu S, Kim DS, et al. CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells. Proc Natl Acad Sci U S A. 2007;104:139–44. doi: 10.1073/pnas.0601947103.PubMedCrossRefGoogle Scholar
  9. 9.
    Borthakur A, Bhattacharyya S, Alrefai WA, Tobacman JK, Ramaswamy K, Dudeja PK. Platelet-activating factor-induced NF-kappaB activation and IL-8 production in intestinal epithelial cells are Bcl10-dependent. Inflamm Bowel Dis. 2010;16:593–603. doi: 10.1002/ibd.21092.PubMedCrossRefGoogle Scholar
  10. 10.
    Marasco D, Stilo R, Sandomenico A, Monti SM, Tizzano B, de Capua A, et al. Generation and functional characterization of a BCL10-inhibitory peptide that represses NF-kappaB activation. Biochem J. 2009;422:553–61. doi: 10.1042/BJ20090055.PubMedCrossRefGoogle Scholar
  11. 11.
    Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev. 2004;18:2195–224. doi: 10.1101/gad.1228704.PubMedCrossRefGoogle Scholar
  12. 12.
    Aggarwal BB. Nuclear factor-kappaB: the enemy within. Cancer Cell. 2004;6:203–8. doi: 10.1016/j.ccr.2004.09.003.PubMedCrossRefGoogle Scholar
  13. 13.
    Mahanivong C, Chen HM, Yee SW, Pan ZK, Dong Z, Huang S. Protein kinase C alpha-CARMA3 signaling axis links Ras to NF-kappa B for lysophosphatidic acid-induced urokinase plasminogen activator expression in ovarian cancer cells. Oncogene. 2008;27:1273–80. doi: 10.1038/sj.onc.1210746.PubMedCrossRefGoogle Scholar
  14. 14.
    Jiang T, Grabiner B, Zhu Y, Jiang C, Li H, You Y, et al. CARMA3 is crucial for EGFR-induced activation of NF-κB and tumor progression. Cancer Res. 2011;71(6):2183–92. doi: 10.1158/0008-5472.CAN-10-3626.PubMedCrossRefGoogle Scholar
  15. 15.
    Rehman AO, Wang CY. CXCL12/SDF-1 alpha activates NF-kappaB and promotes oral cancer invasion through the Carma3/Bcl10/Malt1 complex. Int J Oral Sci. 2009;1:105–18. doi: 10.4248/IJOS.09059.PubMedCrossRefGoogle Scholar
  16. 16.
    Miao Z, Zhao T, Wang Z, Xu Y, Song Y, Wu J, et al. CARMA3 is overexpressed in colon cancer and regulates NF-κB activity and cyclin D1 expression. Biochem Biophys Res Commun. 2012;425:781–7. doi: 10.1016/j.bbrc.2012.07.152.PubMedCrossRefGoogle Scholar
  17. 17.
    Li Z, Qu L, Dong Q, Huang B, Li H, Tang Z, et al. Overexpression of CARMA3 in non-small-cell lung cancer is linked for tumor progression. PLoS One. 2012;7:e36903. doi: 10.1371/journal.pone.0036903.PubMedCrossRefGoogle Scholar
  18. 18.
    Muriel López C, Esteban E, Berros JP, Pardo P, Astudillo A, Izquierdo M, et al. Prognostic factors in patients with advanced renal cell carcinoma. Clin Genitourin Cancer. 2012;10:262–70. doi: 10.1016/j.clgc.2012.06.005.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Guang-Li Wu
    • 1
  • Jian-Lin Yuan
    • 2
  • Xu-Dong Huang
    • 1
  • Jun-Fang Rong
    • 3
  • Li-Xia Zhang
    • 1
  • Yue-Ping Liu
    • 4
  • Fu-Li Wang
    • 2
  1. 1.Department of NephrologyBethune International Peace Hospital of People’s Liberation Army (PLA)ShijiazhuangChina
  2. 2.Department of Urinary Surgery, Xijing HospitalThe Fourth Military Medical UniversityXi’anChina
  3. 3.Department of AnesthesiologyHebei Province General HospitalShijiazhuangChina
  4. 4.Department of Pathology, Tumor Hospital of Hebei ProvinceFourth Hospital of Hebei Medical UniversityShijiazhuangChina

Personalised recommendations