Abstract
Using a panel of cDNA microarrays comprising 47 650 transcript elements, we have carried out a dual-channel analysis of gene expression in 39 resected primary human non-small cell lung tumours versus normal lung tissue. Whilst ∼11 000 elements were scored as differentially expressed at least twofold in at least one sample, 96 transcripts were scored as over-represented fourfold or more in at least seven out of 39 tumours and 30 sequences 16-fold in at least two out of 39 tumours, including 24 transcripts in common. Transcripts (178) were found under-represented fourfold in at least seven out of 39 tumours, 31 of which are under-represented 16-fold in at least two out of 39 lesions. The relative expression levels of representative genes from these lists were analysed by comparative multiplex RT–PCR and found to be broadly consistent with the microarray data. Two dramatically over-represented genes, previously designated as potential tumour suppressors in breast (maspin) and lung and breast (S100A2) cancers, were analysed more extensively and demonstrate the effectiveness of this approach in identifying potential lung cancer diagnostic or therapeutic targets. Whilst it has been reported that S100A2 is downregulated in NSCLC at an early stage, our microarray, cmRT–PCR, Western and immunohistochemistry data indicate that it is strongly expressed in the majority of tumours.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Agrawal D, Chen T, Irby R, Quackenbush J, Chambers AF, Szabo M, Cantor A, Coppola D, Yeatman TJ . 2002 J. Natl. Cancer Inst. 94: 513–521
Bertucci F, Houlgatte R, Nguyen C, Viens P, Jordan BR, Birnbaum D . 2001 Lancet Oncol. 2: 674–682
Bhattacharjee A, Richards WG, Staunton S, Li C, Monti S, Vasa P, Ladd C, Beheshti J, Bueno R, Gillette M, Loda M, Weber G, Mark EJ, Lander ES, Wong W, Johnson BE, Golub TR, Sugarbaker DJ, Meyerson M . 2001 Proc. Natl. Acad. Sci. USA 98: 13790–13795
Bonomi P . 2002 Semin. Oncol. 29: 78–86
Bray F, Sankila R, Ferlay J, Parkin DM . 2002 Eur. J. Cancer 38: 99–166
Ilg EC, Schafer BW, Heizmann CW . 1996 Int. J. Cancer 68: 325–332
Feng G, Xu X, Youssef EM, Lotan R . 2001 Cancer Res. 61: 7999–8004
Fraire AE, Roggli VL, Vollmer RT, Greenberg SD, McGavran MH, Spjut HJ, Yesner R . 1987 Cancer 60: 370–375
Folkman J, Hahnfeldt P, Hlatky L . 2000 Nat. Rev. Mol. Cell Biol. 1: 76–79
Garber ME, Troyanskaya OG, Schluens K, Petersen S, Thaesler Z, Pacyna-Gengelbach M, van de Rijn M, Rosen GD, Perou CM, Whyte RI, Altman RB, Brown PO, Botstein D, Petersen I . 2001 Proc. Natl. Acad. Sci. USA 98: 13784–13789
Giordano TJ, Shedden KA, Schwartz DR, Kuick R, Taylor JM, Lee N, Misek DE, Greenson JK, Kardia SL, Beer DG, Rennert G, Cho KR, Gruber SB, Fearon ER, Hanash S . 2001 Am. J. Pathol. 159: 1231–1238
Hayashi K, Matsuda S, Machida K, Yamamoto T, Fukuda Y, Nimura Y, Hayakawa T, Hamaguchi M . 2001 Cancer Res. 61: 2361–2364
Heighway J, Betticher DC, Knapp T, Hoban PR . 2003 Lung Cancer Vol 2: B Driscoll (ed.) Methods in Molecular Medicine Humana Press, New Jersey
Hough CD, Cho KR, Zonderman AB, Schwartz DR, Morin PJ . 2001 Cancer Res. 61: 3869–3876
Hsieh JC, Kodjabachian L, Rebbert ML, Rattner A, Smallwood PM, Samos CH, Nusse R, Dawid IB, Nathans J . 1999 Nature 398: 431–436
Joos L, He JQ, Shepherdson MB, Connett JE, Anthonisen NR, Pare PD, Sandford AJ . 2002 Hum. Mol. Genet. 11: 569–576
Kim JH, Skates SJ, Uede T, Wong KK, Schorge JO, Feltmate CM, Berkowitz RS, Cramer DW, Mok SC . 2002 JAMA 287: 1671–1679
Kolligs FT, Kolligs B, Hajra KM, Hu G, Tani M, Cho KR, Fearon ER . 2000 Genes Dev. 14: 1319–1331
Lee PD, Sladek R, Greenwood CM, Hudson TJ . 2002 Genome Res. 12: 292–297
Liu D, Rudland PS, Sibson DR, Platt-Higgins A, Barraclough R . 2000 Br. J. Cancer 83: 1473–1479
Maass N, Hojo T, Ueding M, Luttges J, Kloppel G, Jonat W, Nagasaki K . 2001 Clin. Cancer. Res. 7: 812–817
Matsumoto Y, Takano H, Kunishio K, Nagao S, Fojo T . 2001 Jpn. J. Cancer Res. 92: 1133–1137
Nacht M, Dracheva T, Gao Y, Fujii T, Chen Y, Player A, Akmaev V, Cook B, Dufault M, Zhang M, Zhang W, Guo M, Curran J, Han S, Sidransky D, Buetow K, Madden SL, Jen J . 2001 Proc. Natl. Acad. Sci. 98: 15203–15208
Pabon C, Modrusan Z, Ruvolo MV, Coleman IM, Daniel S, Yue H, Arnold Jr LJ . 2001 Biotechniques 31: 874–879
Seftor RE, Seftor EA, Sheng S, Pemberton PA, Sager R, Hendrix MJ . 1998 Cancer Res. 58: 5681–5685
Sunday ME, Haley KJ, Sikorski K, Graham SA, Emanuel RL, Zhang F, Mu Q, Shahsafaei A, Hatzis D . 1999 Oncogene 18: 4336–4347
Thurlbeck WM, Churg AM . (eds) 1995 Pathology of the Lung 2nd Edn Thieme Medical Publishers, Inc: New York p 445
Topcu Z . 2001 J. Clin. Pharm. Ther. 26: 405–416
Umekita Y, Ohi Y, Sagara Y, Yoshida H . 2002 Int. J. Cancer 100: 452–455
Welsh JB, Zarrinkar PP, Sapinoso LM, Kern SG, Behling CA, Monk BJ, Lockhart DJ, Burger RA, Hampton GM . 2001 Proc. Natl. Acad. Sci. USA 98: 1176–1181
Wicki R, Franz C, Scholl FA, Heizmann CW, Schafer BW . 1997 Cell Calcium 22: 243–254
Yue H, Eastman PS, Wang BB, Minor J, Doctolero MH, Nuttall RL, Stack R, Becker JW, Montgomery JR, Vainer M, Johnston R . 2001 Nucleic Acids Res. 29: E41
Zhu Y, Spitz MR, Lei L, Mills GB, Wu X . 2001 Cancer Res. 61: 7825–7829
Acknowledgements
This study would not have been possible without clinical material. We would therefore like to thank the patients who allowed us to use their tissues and we would like to thank the clinical teams in Liverpool and Bern who collected, characterized and stored that material. We would also like to thank Helen Scott, and Melanie Hubert for sectioning, staining and imaging the tissues, Suzanne Watson for the S100A2 IHC, Naomi Bowers for bioinformatics support and Tricia Mitchell for the TaqMan experiments. The Roy Castle Lung Cancer Foundation funded the UK-based component of this work. DC Betticher and D Ratschiller are funded by Swiss Cancer League (Grant KFS 703-8-1998) and the clinical material from the neo-adjuvant patients was collected and analysed by M Gugger as part of SAKK (Swiss Group for Clinical Cancer Research) study 16/96 (chaired by DC Betticher).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Heighway, J., Knapp, T., Boyce, L. et al. Expression profiling of primary non-small cell lung cancer for target identification. Oncogene 21, 7749–7763 (2002). https://doi.org/10.1038/sj.onc.1205979
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205979
Keywords
This article is cited by
-
Nanospan, an alternatively spliced isoform of sarcospan, localizes to the sarcoplasmic reticulum in skeletal muscle and is absent in limb girdle muscular dystrophy 2F
Skeletal Muscle (2017)
-
Consensus reference gene(s) for gene expression studies in human cancers: end of the tunnel visible?
Cellular Oncology (2015)
-
S100A2 protein and non-small cell lung cancer. The dual role concept
Tumor Biology (2014)
-
S100A2 promoter-driven conditionally replicative adenovirus targets non-small-cell lung carcinoma
Gene Therapy (2012)
-
A robust tool for discriminative analysis and feature selection in paired samples impacts the identification of the genes essential for reprogramming lung tissue to adenocarcinoma
BMC Genomics (2011)