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Down-regulation of HLA-A mRNA in peripheral blood mononuclear cell of colorectal cancer

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

It has been demonstrated that the alteration of human leukocyte antigen (HLA) class I expression frequently occurs in colorectal tumor. Previous studies mainly focused on the expression of HLA-A in tumor cells. The expression of HLA-A in peripheral blood mononuclear cells (PBMC) was unknown. To develop a non-invasive diagnostic method for colorectal cancer (CRC), this work investigated the expression of HLA-A mRNA in PBMC in patients with CRC.

Methods

Real-time quantitative RT-PCR was used to study the expression of HLA-A mRNA in PBMC from 48 patients with colorectal cancer, 38 patients with benign colorectal lesions, 20 patients with rheumatoid arthritis, 20 patients with esophageal cancer and 40 healthy individuals. Protein chip was utilized to detect the levels of serum CEA, CA 19-9, and CA 242 in all the cases. Overall results from the two methods were compared.

Results

The relative expression of HLA-A mRNA in PBMC was 1.11 ± 0.45 in healthy group, 0.81 ± 0.42 in benign colorectal lesion group, and 0.39 ± 0.34 in cancer group, respectively. The diagnostic sensitivity of HLA-A mRNA, CEA, CA19-9, and CA242 was 81%, 59%, 61%, and 63%, and their diagnostic specificity was 75%, 64%, 52%, and 67%, respectively.

Conclusions

The expression of HLA-A mRNA in PBMC from colorectal cancer group was significantly lower than those in both benign group and healthy group (P < 0.001). It could be potentially developed as a tumor assistant marker in future.

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References

  1. Pasetto LM, D'Andrea MR, Jirillo A et al (2006) Stable disease in advanced colorectal cancer: therapeutic implications. Anticancer Res 26:511–522

    PubMed  Google Scholar 

  2. Popat S, Zhao D, Chen Z et al (2007) Relationship between chromosome 18q status and colorectal cancer prognosis: a prospective, blinded analysis of 280 patients. Anticancer Res 27:627–633

    PubMed  Google Scholar 

  3. Jemal A, Siegel R, Ward E et al (2006) Cancer statistics. CA Cancer J Clin 56:106–130

    Article  PubMed  Google Scholar 

  4. Cummings LC, Payes JD, Cooper GS (2007) Survival after hepatic resection in metastatic colorectal cancer: a population-based study. Cancer 109:718–726

    Article  PubMed  Google Scholar 

  5. Chen CD, Yen MF, Wang WM et al (2003) A case-cohort study for the disease natural history of adenoma-carcinoma and de novo carcinoma and surveillance of colon and rectum after polypectomy: implication for efficacy of colonoscopy. Br J Cancer 88:1866–1873

    Article  PubMed  Google Scholar 

  6. Vermorken JB, Claessen AM, van Tinteren H et al (1999) Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial. Lancet 353:345–350

    Article  PubMed  CAS  Google Scholar 

  7. Riethmuller G, Schneider Gadicke E, Schlimok G et al (1994) Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes'C colorectal carcinoma. German Cancer Aid 17-1A Study Group. Lancet 343:1177–1183

    Article  PubMed  CAS  Google Scholar 

  8. Moertel CG, Fleming TR, Macdonald JS et al (1990) Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 322:352–358

    Article  PubMed  CAS  Google Scholar 

  9. Moller P, Koretz K, Schlag P et al (1991) Frequency of abnormal expression of HLA-A, B, C and HLA-DR molecules, invariant chain, and LFA-3 (CD58) in colorectal carcinoma and its impact on tumor recurrence. Int J Cancer Suppl 6:155–162

    Article  PubMed  CAS  Google Scholar 

  10. Momburg F, Degener T, Bacchus E et al (1986) Loss of HLA-A, B, C and de novo expression of HLA-D in colorectal cancer. Int J Cancer 37:179–184

    Article  PubMed  CAS  Google Scholar 

  11. McDougall CJ, Ngoi SS, Goldman IS et al (1990) Reduced expression of HLA class I and II antigens in colon cancer. Cancer Res 50:8023–8027

    PubMed  CAS  Google Scholar 

  12. Cordon CC, Fuks Z, Drobnjak M et al (1991) Expression of HLA-A, B, C antigens on primary and metastatic tumor cell populations of human carcinomas. Cancer Res 51:6372–6380

    Google Scholar 

  13. Ruiz CF, Lopez-Nevot MA, Gutierrez J et al (1989) Phenotypic expression of histocompatibility antigens in human primary tumours and metastases. Clin Exp Metastasis 7:213–226

    Article  Google Scholar 

  14. Lopez-Nevot MA, Esteban F, Ferron A et al (1989) HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas. Br J Cancer 59:221–226

    Article  PubMed  CAS  Google Scholar 

  15. Garrido F, Algarra I (2001) MHC antigens and tumor escape from immune surveillance. Adv Cancer Res 83:117–158

    Article  PubMed  CAS  Google Scholar 

  16. Seliger B, Cabrera T, Garrido F et al (2002) HLA class I antigen abnormalities and immune escape by malignant cells. Semin Cancer Biol 12:3–13

    Article  PubMed  CAS  Google Scholar 

  17. Menon AG, Janssen-van Rhijn CM, Morreau H et al (2004) Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis. Lab Invest 84:493–501

    Article  PubMed  CAS  Google Scholar 

  18. Miyagi T, Tatsumi T, Takehara T et al (2003) Impaired expression of proteasome subunits and human leukocyte antigens class I in human colon cancer cells. J Gastroenterol Hepatol 18:32–40

    Article  PubMed  CAS  Google Scholar 

  19. Le Morvan C, Cogne M, Drouet M (2001) HLA-A and HLA-B transcription decrease with ageing in peripheral blood leucocytes. Clin Exp Immunol 125:245–250

    Article  PubMed  Google Scholar 

  20. Le Morvan C, Cogne M, Drouet M (2001) An elevation in the concentration of HLA class I molecules in human blood due to ageing. Mech Ageing Dev 122:335–340

    Article  PubMed  Google Scholar 

  21. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408

    Article  PubMed  CAS  Google Scholar 

  22. Bernards R, Dessain SK, Weinberg RA (1986) N-myc amplification causes down-modulation of MHC class I antigen expression in neuroblastoma. Cell 47:667–674

    Article  PubMed  CAS  Google Scholar 

  23. Versteeg R, van der Minne C, Plomp A et al (1990) N-myc expression switched off and class I human leukocyte antigen expression switched on after somatic cell fusion of neuroblastoma cells. Mol Cell Biol 10:5416–5423

    PubMed  CAS  Google Scholar 

  24. Cheng NC, Beitsma M, Chan A et al (1996) Lack of class I HLA expression in neuroblastoma is associated with high N-myc expression and hypomethylation due to loss of the MEMO-1 locus. Oncogene 13:1737–1744

    PubMed  CAS  Google Scholar 

  25. Gross N, Beck D, Favre S (1990) In vitro modulation and relationship between N-myc and HLA class I RNA steady-state levels in human neuroblastoma cells. Cancer Res 50:7532–7536

    PubMed  CAS  Google Scholar 

  26. Jass JR, Baker K, Zlobec I et al (2006) Advanced colorectal polyps with the molecular and morphological features of serrated polyps and adenomas: concept of a ‘fusion’ pathway to colorectal cancer. Histopathology 49:121–131

    Article  PubMed  CAS  Google Scholar 

  27. Chan TL, Zhao W, Leung SY et al (2003) Cancer Genome Project. BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas. Cancer Res 63:4878–4881

    PubMed  CAS  Google Scholar 

  28. Torlakovic E, Skovlund E, Snover DC et al (2003) Morphologic reappraisal of serrated colorectal polyps. Am J Surg Pathol 27:65–81

    Article  PubMed  Google Scholar 

  29. Goldstein NS, Bhanot P, Odish E et al (2003) Hyperplastic-like colon polyps that preceded microsatellite-unstable adenocarcinomas. Am J Clin Pathol 119:778–796

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the National Basic Research Program of China (2010CB732400), National Natural Science Foundation of China (21075055), the Leading Medical Talents Program from the Department of Health of Jiangsu and the grant from Jiangsu Cancer Hospital (ZQ200904).

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Correspondence to Feng Yan.

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Zhu, MC., Xu, YJ., Zou, X. et al. Down-regulation of HLA-A mRNA in peripheral blood mononuclear cell of colorectal cancer. Int J Colorectal Dis 27, 31–36 (2012). https://doi.org/10.1007/s00384-011-1315-4

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