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Two subclasses of lung squamous cell carcinoma with different gene expression profiles and prognosis identified by hierarchical clustering and non-negative matrix factorization

Oncogene volume 24, pages 7105–7113 (2005)Cite this article

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.

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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.

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Author notes

  1. Kentaro Inamura and Takeshi Fujiwara: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, 135-8550, Tokyo, Japan

    Kentaro Inamura & Yuichi Ishikawa

  2. Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan

    Takeshi Fujiwara, Yujin Hoshida, Takayuki Isagawa, Miyuki Shimane, Shumpei Ishikawa, Hiroyuki Aburatani & Hitoshi Nomura

  3. Chugai Pharmaceutical Company, Tokyo, Japan

    Michael H Jones & Carl Virtanen

  4. Department of Chest Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

    Yukitoshi Satoh, Sakae Okumura & Ken Nakagawa

  5. Kanagawa Cancer Center, Yokohama, Kanagawa, Japan

    Eiju Tsuchiya

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  1. Kentaro Inamura
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Correspondence to Yuichi Ishikawa.

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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

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