Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Whole genome expression profiling of advance stage papillary serous ovarian cancer reveals activated pathways

Abstract

Ovarian cancer is the most lethal type of gynecologic cancer in the Western world. The high case fatality rate is due in part because most ovarian cancer patients present with advanced stage disease which is essentially incurable. In order to obtain a whole genome assessment of aberrant gene expression in advanced ovarian cancer, we used oligonucleotide microarrays comprising over 40 000 features to profile 37 advanced stage papillary serous primary carcinomas. We identified 1191 genes that were significantly (P<0.001) differentially regulated between the ovarian cancer specimens and normal ovarian surface epithelium. The microarray data were validated using real time RT–PCR on 14 randomly selected differentially regulated genes. The list of differentially expressed genes includes ones that are involved in cell growth, differentiation, adhesion, apoptosis and migration. In addition, numerous genes whose function remains to be elucidated were also identified. The microarray data were imported into PathwayAssist software to identify signaling pathways involved in ovarian cancer tumorigenesis. Based on our expression results, a signaling pathway associated with tumor cell migration, spread and invasion was identified as being activated in advanced ovarian cancer. The data generated in this study represent a comprehensive list of genes aberrantly expressed in serous papillary ovarian adenocarcinoma and may be useful for the identification of potentially new and novel markers and therapeutic targets for ovarian cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  • Adib TR, Henderson S, Perrett C, Hewitt D, Bourmpoulia D, Ledermann J and Boshoff C . (2004). Br. J. Cancer, 90, 686–692.

  • Astier A, Manie SN, Law SF, Canty T, Haghayghi N, Druker BJ, Salgia R, Golemis EA and Freedman AS . (1997). Leuk. Lymphoma, 28, 65–72.

  • Auersperg N, Pan J, Grove BD, Peterson T, Fisher J, Maines-Bandiera S, Somasiri A and Roskelley CD . (1999). Proc. Natl. Acad. Sci. USA, 96, 6249–6254.

  • Baciu PC, Suleiman EA, Deryugina EI and Strongin AY . (2003). Exp. Cell Res., 291, 167–175.

  • Bagnato A, Salani D, Di Castro V, Wu-Wong JR, Tecce R, Nicotra MR, Venuti A and Natali PG . (1999). Cancer Res., 59, 720–727.

  • Bagnato A, Tecce R, Di Castro V and Catt KJ . (1997). Cancer Res., 57, 1306–1311.

  • Bao JJ, Le XF, Wang RY, Yuan J, Wang L, Atkinson EN, LaPushin R, Andreeff M, Fang B, Yu Y and Bast Jr RC . (2002). Cancer Res., 62, 7264–7272.

  • Barbieri F, Cagnoli M, Ragni N, Foglia G, Bruzzo C, Pedulla F and Alama A . (1999). Clin. Cancer Res., 5, 1837–1842.

  • Bayani J, Brenton JD, Macgregor PF, Beheshti B, Albert M, Nallainathan D, Karaskova J, Rosen B, Murphy J, Laframboise S, Zanke B and Squire JA . (2002). Cancer Res., 62, 3466–3476.

  • Benjamin Y and Hochberg Y . (1995). J. R. Statist. Soc., 57, 289–300.

  • Booden MA, Eckert LB, Der CJ and Trejo J . (2004). Mol. Cell Biol., 24, 1990–1999.

  • Campbell IG, Freemont PS, Foulkes W and Trowsdale J . (1992). Cancer Res., 52, 5416–5420.

  • Capo-chichi CD, Roland IH, Vanderveer L, Bao R, Yamagata T, Hirai H, Cohen C, Hamilton TC, Godwin AK and Xu XX . (2003). Cancer Res., 63, 4967–4977.

  • Cary LA, Chang JF and Guan JL . (1996). J. Cell Sci., 109 (Part 7), 1787–1794.

  • Darmoul D, Gratio V, Devaud H, Lehy T and Laburthe M . (2003). Am. J. Pathol., 162, 1503–1513.

  • Davidson B, Goldberg I, Berner A, Nesland JM, Givant-Horwitz V, Bryne M, Risberg B, Kristensen GB, Trope CG, Kopolovic J and Reich R . (2001). Am. J. Clin. Pathol., 115, 517–524.

  • Davidson B, Goldberg I, Gotlieb WH, Kopolovic J, Ben-Baruch G, Nesland JM, Berner A, Bryne M and Reich R . (1999). Clin. Exp. Metastasis, 17, 799–808.

  • Dhar KK, Branigan K, Parkes J, Howells RE, Hand P, Musgrove C, Strange RC, Fryer AA, Redman CW and Hoban PR . (1999). Br. J. Cancer, 81, 1174–1181.

  • Ellerbroek SM, Fishman DA, Kearns AS, Bafetti LM and Stack MS . (1999). Cancer Res., 59, 1635–1641.

  • Etienne W, Meyer MH, Peppers J and Meyer Jr RA . (2004). Biotechniques, 36, 618–626.

  • Even-Ram SC, Maoz M, Pokroy E, Reich R, Katz BZ, Gutwein P, Altevogt P and Bar-Shavit R . (2001). J. Biol. Chem., 276, 10952–10962.

  • Fashena SJ, Einarson MB, O'Neill GM, Patriotis C and Golemis EA . (2002). J. Cell Sci., 115, 99–111.

  • Fishman DA, Bafetti LM and Stack MS . (1996). Invas. Metastasis, 16, 150–159.

  • Friedlander ML . (1998). Semin. Oncol., 25, 305–314.

  • Frisch SM, Vuori K, Ruoslahti E and Chan-Hui PY . (1996). J. Cell Biol., 134, 793–799.

  • Gao AG, Lindberg FP, Dimitry JM, Brown EJ and Frazier WA . (1996). J. Cell Biol., 135, 533–544.

  • Gibson MA, Finnis ML, Kumaratilake JS and Cleary EG . (1998). J. Histochem. Cytochem., 46, 871–886.

  • Gibson MA, Leavesley DI and Ashman LK . (1999). J. Biol. Chem., 274, 13060–13065.

  • Godwin AK, Testa JR, Handel LM, Liu Z, Vanderveer LA, Tracey PA and Hamilton TC . (1992). J. Natl. Cancer Inst., 84, 592–601.

  • Hauptmann S, Denkert C, Koch I, Petersen S, Schluns K, Reles A, Dietel M and Petersen I . (2002). Hum. Pathol., 33, 632–641.

  • Hocevar BA, Mou F, Rennolds JL, Morris SM, Cooper JA and Howe PH . (2003). EMBO J., 22, 3084–3094.

  • Hough CD, Sherman-Baust CA, Pizer ES, Montz FJ, Im DD, Rosenshein NB, Cho KR, Riggins GJ and Morin PJ . (2000). Cancer Res., 60, 6281–6287.

  • Hu J, Khanna V, Jones MW and Surti U . (2003). Gynecol. Oncol., 89, 369–375.

  • Imai K, Ohuchi E, Aoki T, Nomura H, Fujii Y, Sato H, Seiki M and Okada Y . (1996). Cancer Res., 56, 2707–2710.

  • Irby RB and Yeatman TJ . (2000). Oncogene, 19, 5636–5642.

  • Ismail RS, Baldwin RL, Fang J, Browning D, Karlan BY, Gasson JC and Chang DD . (2000). Cancer Res., 60, 6744–6749.

  • Israeli O, Gotlieb WH, Friedman E, Goldman B, Ben-Baruch G, Aviram-Goldring A and Rienstein S . (2003). Gynecol. Oncol., 90, 629–636.

  • Iwabuchi H, Sakamoto M, Sakunaga H, Ma YY, Carcangiu ML, Pinkel D, Yang-Feng TL and Gray JW . (1995). Cancer Res., 55, 6172–6180.

  • Jemal A, Murray T, Samuels A, Ghafoor A, Ward E and Thun MJ . (2003). CA Cancer J. Clin., 53, 5–26.

  • Judson PL, He X, Cance WG and Van Le L . (1999). Cancer, 86, 1551–1556.

  • Kreuzer KA, Lass U, Landt O, Nitsche A, Laser J, Ellerbrok H, Pauli G, Huhn D and Schmidt CA . (1999). Clin. Chem., 45, 297–300.

  • Kurochkin IV, Yonemitsu N, Funahashi SI and Nomura H . (2001). Biochem. Biophys. Res. Commun., 280, 340–347.

  • Law SF, Estojak J, Wang B, Mysliwiec T, Kruh G and Golemis EA . (1996). Mol. Cell. Biol., 16, 3327–3337.

  • Livak KJ and Schmittgen TD . (2001). Methods, 25, 402–408.

  • Lozano E, Betson M and Braga VM . (2003). BioEssays, 25, 452–463.

  • Luo RZ, Fang X, Marquez R, Liu SY, Mills GB, Liao WS, Yu Y and Bast RC . (2003). Oncogene, 22, 2897–2909.

  • Mawby WJ, Holmes CH, Anstee DJ, Spring FA and Tanner MJ . (1994). Biochem. J., 304 (Part 2), 525–530.

  • Mok SC, Chan WY, Wong KK, Cheung KK, Lau CC, Ng SW, Baldini A, Colitti CV, Rock CO and Berkowitz RS . (1998). Oncogene, 16, 2381–2387.

  • Molino M, Woolkalis MJ, Reavey-Cantwell J, Pratico D, Andrade-Gordon P, Barnathan ES and Brass LF . (1997). J. Biol. Chem., 272, 11133–11141.

  • Nap M, Vitali A, Nustad K, Bast Jr RC, O'Brien TJ, Nilsson O, Seguin P, Suresh MR, Bormer OP, Saga T, de Bruijn HW, Nozawa S, Kreutz FT, Jette D, Sakahara H, Gadnell M, Endo K, Barlow EH, Warren D, Paus E, Hammarstrom S, Kenemans P and Hilgers J . (1996). Tumour Biol., 17, 325–331.

  • Nobes CD and Hall A . (1995). Cell, 81, 53–62.

  • O'Brien PJ, Molino M, Kahn M and Brass LF . (2001). Oncogene, 20, 1570–1581.

  • Oberst M, Anders J, Xie B, Singh B, Ossandon M, Johnson M, Dickson RB and Lin CY . (2001). Am. J. Pathol., 158, 1301–1311.

  • Oberst MD, Johnson MD, Dickson RB, Lin CY, Singh B, Stewart M, Williams A, al-Nafussi A, Smyth JF, Gabra H and Sellar GC . (2002). Clin. Cancer Res., 8, 1101–1107.

  • Oh J, Takahashi R, Kondo S, Mizoguchi A, Adachi E, Sasahara RM, Nishimura S, Imamura Y, Kitayama H, Alexander DB, Ide C, Horan TP, Arakawa T, Yoshida H, Nishikawa S, Itoh Y, Seiki M, Itohara S, Takahashi C and Noda M . (2001). Cell, 107, 789–800.

  • Ohuchi E, Imai K, Fujii Y, Sato H, Seiki M and Okada Y . (1997). J. Biol. Chem., 272, 2446–2451.

  • Ono K, Tanaka T, Tsunoda T, Kitahara O, Kihara C, Okamoto A, Ochiai K, Takagi T and Nakamura Y . (2000). Cancer Res., 60, 5007–5011.

  • Peng H, Xu F, Pershad R, Hunt KK, Frazier ML, Berchuck A, Gray JW, Hogg D, Bast Jr RC and Yu Y . (2000). Int. J. Cancer, 86, 690–694.

  • Rhee JS and Coussens LM . (2002). Trends Cell Biol., 12, 209–211.

  • Rosano L, Spinella F, Di Castro V, Nicotra MR, Albini A, Natali PG and Bagnato A . (2003). Am. J. Pathol., 163, 753–762.

  • Rosano L, Varmi M, Salani D, Di Castro V, Spinella F, Natali PG and Bagnato A . (2001). Cancer Res., 61, 8340–8346.

  • Sachdev P, Zeng L and Wang LH . (2002). J. Biol. Chem., 277, 17638–17648.

  • Sambrano GR and Coughlin SR . (1999). J. Biol. Chem., 274, 20178–20184.

  • Sasaki H, Sheng Y, Kotsuji F and Tsang BK . (2000). Cancer Res., 60, 5659–5666.

  • Sato H and Seiki M . (1996). J. Biochem. (Tokyo), 119, 209–215.

  • Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E and Seiki M . (1994). Nature, 370, 61–65.

  • Schaller MD, Hildebrand JD and Parsons JT . (1999). Mol. Biol. Cell, 10, 3489–3505.

  • Schaner ME, Ross DT, Ciaravino G, Sorlie T, Troyanskaya O, Diehn M, Wang YC, Duran GE, Sikic TL, Caldeira S, Skomedal H, Tu IP, Hernandez-Boussard T, Johnson SW, O'Dwyer PJ, Fero MJ, Kristensen GB, Borresen-Dale AL, Hastie T, Tibshirani R, van de Rijn M, Teng NN, Longacre TA, Botstein D, Brown PO and Sikic BI . (2003). Mol. Biol. Cell, 14, 4376–4386.

  • Schmitz AA, Govek EE, Bottner B and Van Aelst L . (2000). Exp. Cell Res., 261, 1–12.

  • Schummer M, Ng WV, Bumgarner RE, Nelson PS, Schummer B, Bednarski DW, Hassell L, Baldwin RL, Karlan BY and Hood L . (1999). Gene, 238, 375–385.

  • Schwartz DR, Kardia SL, Shedden KA, Kuick R, Michailidis G, Taylor JM, Misek DE, Wu R, Zhai Y, Darrah DM, Reed H, Ellenson LH, Giordano TJ, Fearon ER, Hanash SM and Cho KR . (2002). Cancer Res., 62, 4722–4729.

  • Scully RE, Young RH and Clement PB . (1998). Tumors of the Ovary, Maldeveloped Gonads, Fallopian Tube, and Broad Ligament. Atlas of Tumor Pathology, Third Series, Fascicle 23. Armed Forces Institute of Pathology: Washington, DC.

    Google Scholar 

  • Sieg DJ, Hauck CR, Ilic D, Klingbeil CK, Schaefer E, Damsky CH and Schlaepfer DD . (2000). Nat. Cell Biol., 2, 249–256.

  • Sounni NE, Devy L, Hajitou A, Frankenne F, Munaut C, Gilles C, Deroanne C, Thompson EW, Foidart JM and Noel A . (2002). FASEB J, 16, 555–564.

  • Span PN, Sweep CG, Manders P, Beex LV, Leppert D and Lindberg RL . (2003). Cancer, 97, 2710–2715.

  • Takeuchi T, Harris JL, Huang W, Yan KW, Coughlin SR and Craik CS . (2000). J. Biol. Chem., 275, 26333–26342.

  • Tapper J, Kettunen E, El-Rifai W, Seppala M, Andersson LC and Knuutila S . (2001). Cancer Genet. Cytogenet., 128, 1–6.

  • Testa JR, Getts LA, Salazar H, Liu Z, Handel LM, Godwin AK and Hamilton TC . (1994). Cancer Res., 54, 2778–2784.

  • Tiruppathi C, Yan W, Sandoval R, Naqvi T, Pronin AN, Benovic JL and Malik AB . (2000). Proc. Natl. Acad. Sci. USA, 97, 7440–7445.

  • Tonin PN, Hudson TJ, Rodier F, Bossolasco M, Lee PD, Novak J, Manderson EN, Provencher D and Mes-Masson AM . (2001). Oncogene, 20, 6617–6626.

  • Wang K, Gan L, Jeffery E, Gayle M, Gown AM, Skelly M, Nelson PS, Ng WV, Schummer M, Hood L and Mulligan J . (1999). Gene, 229, 101–108.

  • Wang L, Hoque A, Luo RZ, Yuan J, Lu Z, Nishimoto A, Liu J, Sahin AA, Lippman SM, Bast Jr RC and Yu Y . (2003). Clin. Cancer Res., 9, 3660–3666.

  • Wang Y, Zhou Y, Szabo K, Haft CR and Trejo J . (2002). Mol. Biol. Cell, 13, 1965–1976.

  • Welsh JB, Zarrinkar PP, Sapinoso LM, Kern SG, Behling CA, Monk BJ, Lockhart DJ, Burger RA and Hampton GM . (2001). Proc. Natl. Acad. Sci. USA, 98, 1176–1181.

  • Wiener JR, Windham TC, Estrella VC, Parikh NU, Thall PF, Deavers MT, Bast RC, Mills GB and Gallick GE . (2003). Gynecol. Oncol., 88, 73–79.

  • Wong KK, Cheng RS and Mok SC . (2001). Biotechniques, 30, 670–675.

  • Yin YJ, Salah Z, Maoz M, Ram SC, Ochayon S, Neufeld G, Katzav S and Bar-Shavit R . (2003). FASEB J, 17, 163–174.

  • Yu Y, Fujii S, Yuan J, Luo RZ, Wang L, Bao J, Kadota M, Oshimura M, Dent SR, Issa JP and Bast Jr RC . (2003). Ann. N. Y. Acad. Sci., 983, 268–277.

  • Yu Y, Xu F, Peng H, Fang X, Zhao S, Li Y, Cuevas B, Kuo WL, Gray JW, Siciliano M, Mills GB and Bast Jr RC . (1999). Proc. Natl. Acad. Sci. USA, 96, 214–219.

  • Zeng L, Sachdev P, Yan L, Chan JL, Trenkle T, McClelland M, Welsh J and Wang LH . (2000). Mol. Cell Biol., 20, 9212–9224.

  • Zhao J, Bian ZC, Yee K, Chen BP, Chien S and Guan JL . (2003). Mol. Cell, 11, 1503–1515.

  • Zhao J, Pestell R and Guan JL . (2001). Mol. Biol. Cell, 12, 4066–4077.

Download references

Acknowledgements

We thank Aaron Bell for technical assistance with RNA isolation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael J Birrer.

Additional information

Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Donninger, H., Bonome, T., Radonovich, M. et al. Whole genome expression profiling of advance stage papillary serous ovarian cancer reveals activated pathways. Oncogene 23, 8065–8077 (2004). https://doi.org/10.1038/sj.onc.1207959

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207959

Keywords

This article is cited by

Search

Quick links