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

Inamura, Kentaro; Fujiwara, Takeshi; Hoshida, Yujin; Isagawa, Takayuki; Jones, Michael H.; Virtanen, Carl; Shimane, Miyuki; Satoh, Yukitoshi; Okumura, Sakae; Nakagawa, Ken; Tsuchiya, Eiju; Ishikawa, Shumpei; Aburatani, Hiroyuki; Nomura, Hitoshi; Ishikawa, Yuichi

doi:10.1038/sj.onc.1208858

Cited by 90 publications

(70 citation statements)

References 31 publications

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“…These findings are supported by expression profiling studies reported by Inamura et al 22 Our microarray data further supported a higher specificity of DSG3 compared with either CK5 or p63. Only when combining both, did CK5 and p63 achieve a comparable specificity.…”

Section: Discussionsupporting

confidence: 81%

“…Our results showed that DSG3 staining can be heterogeneous, seen in as little as 5% of cells. However, the high DSG3 expression in AD is more difficult to reconcile and differs from several published oligonucleotide microarray data 22,24,25 and our LCM-derived microarray data on lung. Furthermore expression of DSG3 in ADs would not be predicted based by its biological role.…”

Section: Discussioncontrasting

confidence: 38%

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The Role of Desmoglein-3 in the Diagnosis of Squamous Cell Carcinoma of the Lung

Savcı-Heijink

Kosari

Aubry

et al. 2009

The American Journal of Pathology

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Results from several microarray-based studies have led to the identification of up-regulated expression levels of the DSG3 gene in pulmonary squamous cell carcinomas (SQCCs). The purpose of this study was to determine the role of DSG3 expression in the diagnosis of SQCCs of the lung and to compare DSG3 with p63, CK5, and CK6, as markers of squamous cell differentiation. Expression of DSG3 mRNA was evaluated in bulk laser capture microdissection-derived microarray data and by quantitative reverse transcription PCR on both SQCCs and adenocarcinomas. Expression levels of p63, CK5, and CK6 were evaluated in microarray data from the same set. An immunohistochemical study using antibodies directed against DSG3, p63, and CK5/6 was also performed. DSG3 was over-expressed in SQCCs but had very limited expression in both adenocarcinomas and nonneoplastic lungs. The microarray data showed that DSG3 had a sensitivity and specificity of 88% and 98%, respectively, in detecting SQCC versus adenocarcinoma. In comparison, sensitivity and specificity was 92% and 82% for p63, and 85% and 96% for CK5, respectively. The correlation coefficient between the microarray and immunohistochemical data for these genes was greater than or equal to 0.9. Using immunohistochemistry , sensitivity and specificity of DSG3 for lung cancers were 98% and 99% , respectively. Therefore , DSG3 can be a useful ancillary marker to separate SQCC from other subtypes of lung cancer.

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Section: Discussionsupporting

confidence: 81%

Section: Discussioncontrasting

confidence: 38%

The Role of Desmoglein-3 in the Diagnosis of Squamous Cell Carcinoma of the Lung

Savcı-Heijink

Kosari

Aubry

et al. 2009

The American Journal of Pathology

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“…In particular, there is a considerable overlap in genes or gene families (CCNB2, CDC45L, MAD2L1, KIF23, PTTG2, ORC6L, and KNSL6) identified between the current and the breast cancer study (31). Moreover, similar results have been obtained recently for aggressive neuroblastoma (32) and poor prognosis lung squamous cell carcinoma (33). Therefore, a cell cycle or cell proliferation signature might be a common theme of aggressive or in particular of advanced stages of several malignancies associated with poor therapy outcome.…”

Section: Discussionsupporting

confidence: 70%

Expression of Late Cell Cycle Genes and an Increased Proliferative Capacity Characterize Very Early Relapse of Childhood Acute Lymphoblastic Leukemia

Kirschner-Schwabe

Lottaz

Tödling

et al. 2006

Clinical Cancer Research

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Purpose: In childhood acute lymphoblastic leukemia (ALL), f25% of patients suffer from relapse. In recurrent disease, despite intensified therapy, overall cure rates of 40% remain unsatisfactory and survival rates are particularly poor in certain subgroups. The probability of long-term survival after relapse is predicted from well-established prognostic factors (i.e., time and site of relapse, immunophenotype, and minimal residual disease). However, the underlying biological determinants of these prognostic factors remain poorly understood. Experimental Design: Aiming at identifying molecular pathways associated with these clinically well-defined prognostic factors, we did gene expression profiling on 60 prospectively collected samples of first relapse patients enrolled on the relapse trial ALL-REZ BFM 2002 of the Berlin-Frankfurt-Mu« nster study group. Results: We show here that patients with very early relapse of ALL are characterized by a distinctive gene expression pattern.We identified a set of 83 genes differentially expressed in very early relapsed ALL compared with late relapsed disease. The vast majority of genes were up-regulated and many were late cell cycle genes with a function in mitosis. In addition, samples from patients with very early relapse showed a significant increase in the percentage of S and G 2 -M phase cells and this correlated well with the expression level of cell cycle genes. Conclusions: Very early relapse of ALL is characterized by an increased proliferative capacity of leukemic blasts and up-regulated mitotic genes.The latter suggests that novel drugs, targeting late cell cycle proteins, might be beneficial for these patients that typically face a dismal prognosis.Acute lymphoblastic leukemia (ALL) is the most common malignant disease in children (1). Although event-free survival rates range between 70% and 75%, relapse of ALL remains the fourth most frequent diagnosis in childhood cancer affecting 25% of ALL patients (2). At relapse, overall cure rates of f40% remain unsatisfactory and survival rates are particularly poor in certain subgroups (3). Treatment of relapse usually implies intensified polychemotherapy containing high-dose elements. Although in most children, second remissions can be induced high-risk patients require further treatment intensification by stem cell transplantation. Stem cell transplantation provides a better relapse-free survival rate than chemotherapy alone but is also associated with higher treatment-related morbidity and mortality rates (2). Thus, alternative treatment strategies are needed to improve the treatment and outcome of patients with relapsed ALL.In the treatment of ALL relapse, intensity of chemotherapy and stem cell transplantation are indicated by well-established prognostic factors (summarized in ref.2), with the most evident being the time to relapse. Early recurrence of disease with respect to frontline therapy affects f60% of patients and is associated with a high rate of nonresponse to treatment, shorter duration of second ...

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“…This is exemplified by the work of Inamura et al (18). Inamura et al analyzed tumor and normal lung samples by hierarchical clustering with the nonnegative matrix factorization approach and divided lung squamous cell carcinoma into two distinct subclasses, which showed the significant differences in clinical outcome and molecular characteristics (18).…”

Section: Tumor Classification and Clusteringmentioning

confidence: 99%

Statistical Analysis of DNA Microarray Data in Cancer Research

Fan

Ren²

2006

Clinical Cancer Research

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Microarray techniques have been widely used to monitor gene expression in many areas of biomedical research. They have been widely used for tumor diagnosis and classification, prediction of prognoses and treatment, and understanding of molecular mechanisms, biochemical pathways, and gene networks. Statistical methods are vital for these scientific endeavors. This article reviews recent developments of statistical methods for analyzing data from microarray experiments. Emphasis has been given to normalization of expression from multiple arrays, selecting significantly differentially expressed genes, tumor classifications, and gene expression pathways and networks.

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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

Cited by 90 publications

References 31 publications

The Role of Desmoglein-3 in the Diagnosis of Squamous Cell Carcinoma of the Lung

The Role of Desmoglein-3 in the Diagnosis of Squamous Cell Carcinoma of the Lung

Expression of Late Cell Cycle Genes and an Increased Proliferative Capacity Characterize Very Early Relapse of Childhood Acute Lymphoblastic Leukemia

Statistical Analysis of DNA Microarray Data in Cancer Research

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