Skip to main content

Advertisement

SpringerLink
Log in

Gene expression patterns as marker for 5-year postoperative prognosis of primary breast cancers

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To establish the novel prognostic markers for breast cancer, gene expression profile was examined genome-wide.

Methods

We used cDNA microarray consisting of 18,432 human genes to compare genome-wide expression profiles of eight primary breast cancers, four from patients who died of breast cancer within 5 years after surgery (5D group) and four who survived disease-free for more than 5 years (5S group).

Results

We identified 21 genes whose expression was greater in tumors from the 5D group than in 5S tumors, and 23 with higher expression in the 5S group than in the 5D group. We established a Prognostic Index (PI) for prediction of postoperative prognosis, based on the aberrant expression profiles of ten of those genes. Among 20 additional cases chosen blindly, ten presented with high prognostic scores (>7, good) according to the PI; the remaining ten cases revealed scores <7 (poor). The PI predicted the actual 5-year clinical outcomes of these 20 cases with 100% accuracy.

Conclusion

Our PI system is reliable in clinical settings for predicting postoperative risk for breast cancer. The extensive list of genes provides valuable information about progression of breast cancer and suggests potential target molecules for treating this disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Anonymous (1989) The general rules for clinical and pathological recording of breast cancer. Japanese Breast Cancer Society. Jpn J Surg 19:612–32

    PubMed  Google Scholar 

  • Carr JA, Havstad S, Zarbo RJ, Divine G, Mackowiak P, Velanovich V (2000) The association of HER-2/neu amplification with breast cancer recurrence. Arch Surg 135:1469–1474

    Article  CAS  PubMed  Google Scholar 

  • Costa SD, Lange S, Klinga K, Merkle E, Kaufmann M (2002) Factors influencing the prognostic role of oestrogen and progesterone receptor levels in breast cancer--results of the analysis of 670 patients with 11 years of follow-up. Eur J Cancer 38:1329–1334

    Article  CAS  PubMed  Google Scholar 

  • Couzin J (2002) Genomics. Taking aim at Celera’s shotgun. Science 295:1817

    Article  CAS  Google Scholar 

  • Dawson PJ, Ferguson DJ, Karrison T (1982) The pathological findings of breast cancer in patients surviving 25 years after radical mastectomy. Cancer 50:2131–2138

    CAS  PubMed  Google Scholar 

  • Egawa C, Miyoshi Y, Taguchi T, Tamaki Y, Noguchi S (2002) High BRCA2 mRNA expression predicts poor prognosis in breast cancer patients. Int J Cancer 98:879–882

    Article  CAS  PubMed  Google Scholar 

  • Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19:403–410

    CAS  PubMed  Google Scholar 

  • Hirano A, Utada Y, Haga S, Kajiwara T, Sakamoto G, Kasumi F, Nakamura Y, Emi M (2001) Allelic losses as prognostic markers for breast cancers. Int J Clin Oncol 6:6–12

    CAS  PubMed  Google Scholar 

  • Huang E, Cheng SH, Dressman H, Pittman J, Tsou MH, Horng CF, Bild A, Iversen ES, Liao M, Chen CM, West M, Nevins JR, Huang AT (2003) Gene expression predictors of breast cancer outcomes. Lancet 361:1590–1596

    Article  CAS  PubMed  Google Scholar 

  • Hupperets PS, Volovics L, Schouten LJ, Jager JJ, Schouten HC, Hillen HF, Blijham GH (1997) The prognostic significance of steroid receptor activity in tumor tissues of patients with primary breast cancer. Am J Clin Oncol 20:546–551

    Article  CAS  PubMed  Google Scholar 

  • Manos EJ, Jones DA (2001) Assessment of tumor necrosis factor receptor and Fas signaling pathways by transcriptional profiling. Cancer Res 61:433–438

    CAS  PubMed  Google Scholar 

  • McPherson JD, Marra M, Hillier L, Waterston RH, Chinwalla A, Wallis J, Sekhon M, Wylie K, Mardis ER, Wilson RK, Fulton R, Kucaba TA, Wagner-McPherson C, Barbazuk WB, Gregory SG, Humphray SJ, French L, Evans RS, Bethel G, Whittaker A, Holden JL, McCann OT, Dunham A, Soderlund C, Scott CE, Bentley DR, Schuler G, Chen HC, Jang W, Green ED, Idol JR, Maduro VV, Montgomery KT, Lee E, Miller A, Emerling S, Kucherlapati, Gibbs R, Scherer S, Gorrell JH, Sodergren E, Clerc-Blankenburg K, Tabor P, Naylor S, Garcia D, de Jong PJ, Catanese JJ, Nowak N, Osoegawa K, Qin S, Rowen L, Madan A, Dors M, Hood L, Trask B, Friedman C, Massa H, Cheung VG, Kirsch IR, Reid T, Yonescu R, Weissenbach J, Bruls T, Heilig R, Branscomb E, Olsen A, Doggett N, Cheng JF, Hawkins T, Myers RM, Shang J, Ramirez L, Schmutz J, Velasquez O, Dixon K, Stone NE, Cox DR, Haussler D, Kent WJ, Furey T, Rogic S, Kennedy S, Jones S, Rosenthal A, Wen G, Schilhabel M, Gloeckner G, Nyakatura G, Siebert R, Schlegelberger B, Korenberg J, Chen XN, Fujiyama A, Hattori M, Toyoda A, Yada T, Park HS, Sakaki Y, Shimizu N, Asakawa S, et al (2001) A physical map of the human genome. Nature 409:934–941

    Article  CAS  PubMed  Google Scholar 

  • Miyoshi Y, Ando A, Egawa C, Taguchi T, Tamaki Y, Tamaki H, Sugiyama H, Noguchi S (2002) High expression of Wilms’ tumor suppressor gene predicts poor prognosis in breast cancer patients. Clin Cancer Res 8:1167–1171

    CAS  PubMed  Google Scholar 

  • Neckers L (2002) Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol Med 8:S55–61

    Article  CAS  PubMed  Google Scholar 

  • Ono K, Tanaka T, Tsunoda T, Kitahara O, Kihara C, Okamoto A, Ochiai K, Takagi T, Nakamura Y (2000) Identification by cDNA microarray of genes involved in ovarian carcinogenesis. Cancer Res 60:5007–5011

    CAS  PubMed  Google Scholar 

  • Powell BL, Bydder S, Grieu F, Gnanasampanthan G, Elsaleh H, Seshadri R, Berns EM, Iacopetta B (2001) Prognostic value of TP53 gene mutation in adjuvant treated breast cancer patients. Breast Cancer Res Treat 69:65–68

    Article  CAS  PubMed  Google Scholar 

  • Ross CD, Gomaa MA, Gillies E, Juengel R, Medina JE (2000) Tumor grade, microvessel density, and activities of malate dehydrogenase, lactate dehydrogenase, and hexokinase in squamous cell carcinoma. Otolaryngol Head Neck Surg 122:195–200

    CAS  PubMed  Google Scholar 

  • Rudolph P, Olsson H, Bonatz G, Ratjen V, Bolte H, Baldetorp B, Ferno M, Parwaresch R, Alm P (1999) Correlation between p53, c-erbB-2, and topoisomerase II alpha expression, DNA ploidy, hormonal receptor status and proliferation in 356 node-negative breast carcinomas: prognostic implications. J Pathol 187:207–216

    Article  CAS  PubMed  Google Scholar 

  • Seshadri R, Leong AS, McCaul K, Firgaira FA, Setlur V, Horsfall DJ (1996) Relationship between p53 gene abnormalities and other tumour characteristics in breast-cancer prognosis. Int J Cancer 69:135–141

    Article  CAS  PubMed  Google Scholar 

  • van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ, Parrish M, Atsma D, Witteveen A, Glas A, Delahaye L, van der Velde T, Bartelink H, Rodenhuis S, Rutgers ET, Friend SH, Bernards R (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999–2009

    Article  PubMed  Google Scholar 

  • van ‘t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–536

    Article  PubMed  Google Scholar 

  • Xie D, Jauch A, Miller CW, Bartram CR, Koeffler HP (2002) Discovery of over-expressed genes and genetic alterations in breast cancer cells using a combination of suppression subtractive hybridization, multiplex FISH and comparative genomic hybridization. Int J Oncol 21:499–507

    CAS  PubMed  Google Scholar 

  • Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP (2002) Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res 30:e15

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Shizuyo Miyamoto and Naoko Shimbo for excellent technical assistance, Mihoko Tsuruta, Mayumi Tanaka, and Kyoko Shimizu for secretarial assistance. This work was supported by special grants for Strategic Advanced Research on “Cancer” from the Ministry of Education, Science, Sports and Culture of Japan; and by a Research for the Future Program Grant of The Japan Society for the Promotion of Science

Author information

Authors and Affiliations

  1. Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, 211-8533, Kawasaki, Japan

    Masamitsu Onda, Mitsuru Emi, Hisaki Nagai, Takemitsu Nagahata, Kouji Tsumagari & Takashi Fujimoto

  2. The Cancer Institute, Kami-Ikebukuro, Tokyo, Japan

    Futoshi Akiyama, Goi Sakamoto, Masujirou Makita, Fujio Kasumi & Yoshio Miki

  3. SNP Research Center, RIKEN (Institute of Physical and Chemical Research), Suehiro-cho, Yokohama, Japan

    Toshihiro Tanaka & Tatsuhiko Tsunoda

  4. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    Toshihiro Tanaka & Yusuke Nakamura

Authors
  1. Masamitsu Onda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mitsuru Emi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hisaki Nagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takemitsu Nagahata
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kouji Tsumagari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takashi Fujimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Futoshi Akiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Goi Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Masujirou Makita
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Fujio Kasumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yoshio Miki
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Toshihiro Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tatsuhiko Tsunoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Yusuke Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mitsuru Emi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Onda, M., Emi, M., Nagai, H. et al. Gene expression patterns as marker for 5-year postoperative prognosis of primary breast cancers. J Cancer Res Clin Oncol 130, 537–545 (2004). https://doi.org/10.1007/s00432-004-0574-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-004-0574-7

Keywords

Search

Navigation