Tumor Biology

, Volume 35, Issue 5, pp 4419–4423 | Cite as

Loss of CSMD1 or 2 may contribute to the poor prognosis of colorectal cancer patients

  • Rui Zhang
  • Chun SongEmail author
Research Article


CUB and sushi multiple domain protein 1 (CSMD1) is a candidate tumor suppressor gene. The three members of CSMD family have very similar structures, each consisting of 14 CUB domains separated from one another by a sushi domain, an additional uninterrupted array of sushi domains, a single transmembrane domain, and a short cytoplasmic tail. In this work, we aimed to study the protein and mRNA levels of the CSMD1, CSMD2, and CSMD3 and evaluate their prognostic importance in colorectal cancer. Reduced expressions of these three proteins were detected in colorectal cancer tissues by comparing matched normal tissues. Low CSMD2 expression was significantly associated with differentiation, lymphatic invasion, and tumor size. CSMD3 was associated with differentiation and lymphatic invasion. CSMD1 and CSMD2 expressions were associated with overall survival. This study offers convincing evidence for the first time that the three genes of CSMD family were downregulated in the patients with colorectal cancer and may be used as predictors of colorectal cancer.


Colorectal cancer CSMD Prognosis Clinical feature Survival rate 



We appreciate the thoughtful advice of Ya-Nan Xing (China Medical University).

Conflicts of interest



  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Kraus DM, Elliott GS, Chute H, Horan T, Pfenninger KH, Sanford SD, et al. CSMD1 is a novel multiple domain complement-regulatory protein highly expressed in the central nervous system and epithelial tissues. J Immunol. 2006;176:4419–30.CrossRefPubMedGoogle Scholar
  3. 3.
    Sun PC, Uppaluri R, Schmidt AP, Pashia ME, Quant EC, Sunwoo JB, et al. Transcript map of the 8p23 putative tumor suppressor region. Genomics. 2001;75:17–25.CrossRefPubMedGoogle Scholar
  4. 4.
    Kamal M, Shaaban AM, Zhang L, Walker C, Gray S, Thakker N, et al. Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma. Breast Cancer Res Treat. 2010;121:555–63.CrossRefPubMedGoogle Scholar
  5. 5.
    Ma C, Quesnelle KM, Sparano A, Rao S, Park MS, Cohen MA, et al. Characterization CSMD1 in a large set of primary lung, head and neck, breast and skin cancer tissues. Cancer Biol Ther. 2009;8:907–16.CrossRefPubMedGoogle Scholar
  6. 6.
    Lau WL, Scholnick SB. Identification of two new members of the CSMD gene family small star, filled. Genomics. 2003;82:412–5.CrossRefPubMedGoogle Scholar
  7. 7.
    Floris C, Rassu S, Boccone L, Gasperini D, Cao A, Crisponi L. Two patients with balanced translocations and autistic disorder: CSMD3 as a candidate gene for autism found in their common 8q23 breakpoint area. Eur J Hum Genet. 2008;16:696–704.CrossRefPubMedGoogle Scholar
  8. 8.
    Tang MR, Wang YM, Guo S, Han SY, Wang D. CSMD1 exhibits antitumor activity in A375 melanoma cells through activation of the Smad pathway. Apoptosis. 2012;17:927–37.CrossRefPubMedGoogle Scholar
  9. 9.
    Midorikawa Y, Yamamoto S, Tsuji S, Kamimura N, Ishikawa S, Igarashi H, et al. Allelic imbalances and homozygous deletion on 8p23.2 for stepwise progression of hepatocarcinogenesis. Hepatology. 2009;49:513–22.CrossRefPubMedGoogle Scholar
  10. 10.
    Henshall SM, Afar DE, Hiller J, Horvath LG, Quinn DI, Rasiah KK, et al. Survival analysis of genome-wide gene expression profiles of prostate cancers identifies new prognostic targets of disease relapse. Cancer Res. 2003;63:4196–203.PubMedGoogle Scholar
  11. 11.
    Paris PL, Andaya A, Fridlyand J, Jain AN, Weinberg V, Kowbel D, et al. Whole genome scanning identifies genotypes associated with recurrence and metastasis in prostate tumors. Hum Mol Genet. 2004;13:1303–13.CrossRefPubMedGoogle Scholar
  12. 12.
    Shull AY, Clendenning ML, Ghoshal-Gupta S, Farrell CL, Vangapandu HV, Dudas L, et al. Somatic mutations, allele loss, and DNA methylation of the Cub and sushi multiple domains 1 (CSMD1) gene reveals association with early age of diagnosis in colorectal cancer patients. PLoS One. 2013;8:e58731.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Liu P, Morrison C, Wang L, Xiong D, Vedell P, Cui P, et al. Identification of somatic mutations in non-small cell lung carcinomas using whole-exome sequencing. Carcinogenesis. 2012;33:1270–6.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Boon K, Osorio EC, Greenhut SF, Schaefer CF, Shoemaker J, Polyak K, et al. An anatomy of normal and malignant gene expression. Proc Natl Acad Sci U S A. 2002;99:11287–92.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Stein JL, Hua X, Lee S, Ho AJ, Leow AD, Toga AW, et al. Voxelwise genome-wide association study (vGWAS). Neuroimage. 2010;53:1160–74.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Intestine SurgeryLiaoning Cancer Hospital and InstituteShenyangChina

Personalised recommendations