Abstract
Current clinical and histopathological criteria used to define lung squamous cell carcinomas (SCCs) are insufficient to predict clinical outcome. To make a clinically useful classification by gene expression profiling, we used a 40 386 element cDNA microarray to analyse 48 SCC, nine adenocarcinoma, and 30 normal lung samples. Initial analysis by hierarchical clustering (HC) allowed division of SCCs into two distinct subclasses. An additional independent round of HC induced a similar partition and consensus clustering with the non-negative matrix factorization approach indicated the robustness of this classification. Kaplan–Meier analysis with the log-rank test pointed to a nonsignificant difference in survival (P=0.071), but the likelihood of survival to 6 years was significantly different between the two groups (40.5 vs 81.8%, P=0.014, Z-test). Biological process categories characteristic for each subclass were identified statistically and upregulation of cell-proliferation-related genes was evident in the subclass with poor prognosis. In the subclass with better survival, genes involved in differentiated intracellular functions, such as the MAPKKK cascade, ceramide metabolism, or regulation of transcription, were upregulated. This work represents an important step toward the identification of clinically useful classification for lung SCC.
Similar content being viewed by others
References
Amatschek S, Koenig U, Auer H, Steinlein P, Pacher M, Gruenfelder A, Dekan G, Vogl S, Kubista E, Heider KH, Stratowa C, Schreiber M and Sommergruber W . (2004). Cancer Res., 64, 844–856.
Arboleda MJ, Lyons JF, Kabbinavar FF, Bray MR, Snow BE, Ayala R, Danino M, Karlan BY and Slamon DJ . (2003). Cancer Res., 63, 196–206.
Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM and Sherlock G . (2000). Nat. Genet., 25, 25–29.
Bhattacharjee A, Richards WG, Staunton J, 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 and Meyerson M . (2001). Proc. Natl. Acad. Sci. USA, 98, 13790–13795.
Borczuk AC, Gorenstein L, Walter KL, Assaad AA, Wang L and Powell CA . (2003). Am. J. Pathol., 163, 1949–1960.
Brunet JP, Tamayo P, Golub TR and Mesirov JP . (2004). Proc. Natl. Acad. Sci. USA, 101, 4164–4169.
Deiss LP, Feinstein E, Berissi H, Cohen O and Kimchi A . (1995). Genes Dev., 9, 15–30.
Esteller M, Corn PG, Baylin SB and Herman JG . (2001). Cancer Res., 61, 3225–3229.
Fukumoto S, Yamauchi N, Moriguchi H, Hippo Y, Watanabe A, Shibahara J, Taniguchi H, Ishikawa S, Ito H, Yamamoto S, Iwanari H, Hironaka M, Ishikawa Y, Niki T, Sohara Y, Kodama T, Nishimura M, Fukayama M, Dosaka-Akita H and Aburatani H . (2005). Clin. Cancer Res., 11, 1776–1785.
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 and Petersen I . (2001). Proc. Natl. Acad. Sci. USA, 98, 13784–13789.
Grille SJ, Bellacosa A, Upson J, Klein-Szanto AJ, van Roy F, Lee-Kwon W, Donowitz M, Tsichlis PN and Larue L . (2003). Cancer Res., 63, 2172–2178.
Helin K, Wu CL, Fattaey AR, Lees JA, Dynlacht BD, Ngwu C and Harlow E . (1993). Genes Dev., 7, 1850–1861.
Hibi K, Trink B, Patturajan M, Westra WH, Caballero OL, Hill DE, Ratovitski EA, Jen J and Sidransky D . (2000). Proc. Natl. Acad. Sci. USA, 97, 5462–5467.
Hosack DA, Dennis G, Sherman BT, Lane HC and Lempicki RA . (2003). Genome Biol., 4, R70.
Ichikawa S, Sakiyama H, Suzuki G, Hidari KI and Hirabayashi Y . (1996). Proc. Natl. Acad. Sci. USA, 93, 4638–4643.
Jones MH, Virtanen C, Honjoh D, Miyoshi T, Satoh Y, Okumura S, Nakagawa K, Nomura H and Ishikawa Y . (2004). Lancet, 363, 775–781.
Kawai T, Akira S and Reed JC . (2003). Mol. Cell. Biol., 23, 6174–6186.
Kettunen E, Anttila S, Seppanen JK, Karjalainen A, Edgren H, Lindstrom I, Salovaara R, Nissen AM, Salo J, Mattson K, Hollmen J, Knuutila S and Wikman H . (2004). Cancer Genet. Cytogenet., 149, 98–106.
Lee DD and Seung HS . (1999). Nature, 401, 788–791.
Mehlen P, Rabizadeh S, Snipas SJ, Assa-Munt N, Salvesen GS and Bredesen DE . (1998). Nature, 395, 801–804.
Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR and Bradley A . (1999). Nature, 398, 708–713.
Miura K, Bowman ED, Simon R, Peng AC, Robles AI, Jones RT, Katagiri T, He P, Mizukami H, Charboneau L, Kikuchi T, Liotta LA, Nakamura Y and Harris CC . (2002). Cancer Res., 62, 3244–3250.
Miyoshi T, Satoh Y, Okumura S, Nakagawa K, Shirakusa T, Tsuchiya E and Ishikawa Y . (2003). Am. J. Surg. Pathol., 27, 101–109.
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 and Jen J . (2001). Proc. Natl. Acad. Sci. USA, 98, 15203–15208.
Palackal NT, Lee SH, Harvey RG, Blair IA and Penning TM . (2002). J. Biol. Chem., 277, 24799–24808.
Pulling LC, Vuillemenot BR, Hutt JA, Devereux TR and Belinsky SA . (2004). Cancer Res., 64, 3844–3848.
Rebhun JF, Castro AF and Quilliam LA . (2000). J. Biol. Chem., 275, 34901–34908.
Taylor SS, Ha E and McKeon F . (1998). J. Cell Biol., 142, 1–11.
Tomida S, Koshikawa K, Yatabe Y, Harano T, Ogura N, Mitsudomi T, Some M, Yanagisawa K, Takahashi T, Osada H and Takahashi T . (2004). Oncogene, 23, 5360–5370.
Virtanen C, Ishikawa Y, Honjoh D, Kimura M, Shimane M, Miyoshi T, Nomura H and Jones MH . (2002). Proc. Natl. Acad. Sci. USA, 99, 12357–12362.
Wikman H, Seppanen JK, Sarhadi VK, Kettunen E, Salmenkivi K, Kuosma E, Vainio-Siukola K, Nagy B, Karjalainen A, Sioris T, Salo J, Hollmen J, Knuutila S and Anttila S . (2004). J. Pathol., 203, 584–593.
Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C and McKeon F . (1999). Nature, 398, 714–718.
Yoo SH, Park YS, Kim HR, Sung SW, Kim JH, Shim YS, Lee SD, Choi YL, Kim MK and Chung DH . (2003). Lung Cancer, 42, 195–202.
Acknowledgements
We thank Mr Shogo Yamamoto for technical advice and suggestions; Mr Atsushi Kobayashi, Ms Mio Kato, Ms Kazuko Yokokawa, Mr Motoyoshi Iwakoshi, Ms Miyuki Kogure, and Ms Tomoyo Kakita for their technical assistance; and Ms Chisato Kakuta for secretarial work. Parts of this study were supported financially by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science; and Technology, and by grants from the Ministry of Health, Labour and Welfare, the Smoking Research Foundation, and the Vehicle Racing Commemorative Foundation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Inamura, K., Fujiwara, T., Hoshida, Y. et al. Two subclasses of lung squamous cell carcinoma with different gene expression profiles and prognosis identified by hierarchical clustering and non-negative matrix factorization. Oncogene 24, 7105–7113 (2005). https://doi.org/10.1038/sj.onc.1208858
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1208858
- Springer Nature Limited
Keywords
This article is cited by
-
Machine learning-based pathomics signature could act as a novel prognostic marker for patients with clear cell renal cell carcinoma
British Journal of Cancer (2022)
-
Identification of transcriptional subtypes in lung adenocarcinoma and squamous cell carcinoma through integrative analysis of microarray and RNA sequencing data
Scientific Reports (2021)
-
Comprehensive analysis of the tumor immune micro-environment in non-small cell lung cancer for efficacy of checkpoint inhibitor
Scientific Reports (2018)
-
NMF versus ICA for blind source separation
Advances in Data Analysis and Classification (2017)
-
Aldo-keto reductases are biomarkers of NRF2 activity and are co-ordinately overexpressed in non-small cell lung cancer
British Journal of Cancer (2016)