cDNA microarray analysis of gene expression in pathologic stage IA nonsmall cell lung carcinomas

Nakamura, Hiroki; Saji, Hisashi; Ogata, Akihiko; Hosaka, Makoto; Hagiwara, Masaru; Saijo, Takamoto; Kawasaki, Norihito; Kato, Harubumi

doi:10.1002/cncr.11406

Cited by 34 publications

(21 citation statements)

References 28 publications

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“…Several lung cancer microarray studies have reported geneexpression changes with potentially significant prognostic impact, encoding for proteins that are expressed by stromal cells (3,25). These studies were performed on RNA isolated from wholetumor tissues, without prior separation of stromal and tumor cells; thus, the cellular origin of these gene-expression changes was largely uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…Non-small cell lung carcinoma (NSCLC) accounts for 85% of all lung cancers. One of the most consistent histological features of cancer cell invasion is the appearance of desmoplasia: stromal changes characterized by the activation of stromal fibroblasts into carcinoma-associated fibroblasts (CAFs), increased matrix protein disposition, new blood vessel formation, and immune cell infiltration (2,3). These changes have been reported to promote tumor cell growth, invasion, metastases, and resistance to treatment as well as to mediate immune reaction against tumor cells (2,4,5).…”

mentioning

confidence: 99%

“…These changes have been reported to promote tumor cell growth, invasion, metastases, and resistance to treatment as well as to mediate immune reaction against tumor cells (2,4,5). Published prognostic gene signatures for NSCLC have included genes encoding for ECM proteins such as collagens 1A1, 1A2, and 9; glypican 3; intercellular adhesion molecule 1 (ICAM-1); laminin B1; selectin L; selectin P; and secreted protein acidic and rich in cysteine (SPARC) (3,5). Furthermore, stromal elements, including PDGF-C, VEGF-A, IL-8, endothelin-1 (EDN1), osteopontin (SPP1), and the chemokine CXCL1, recently have been suggested as potential therapeutic targets in skin and breast cancers (4,6).…”

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confidence: 99%

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Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer

Navab

Strumpf

Bandarchi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

321

302

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The tumor microenvironment strongly influences cancer development, progression, and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC. We demonstrate that CAFs have greater ability than NFs to enhance the tumorigenicity of lung cancer cell lines. Microarray gene-expression analysis of the 15 matched CAF and NF cell lines identified 46 differentially expressed genes, encoding for proteins that are significantly enriched for extracellular proteins regulated by the TGF-β signaling pathway. We have identified a subset of 11 genes (13 probe sets) that formed a prognostic gene-expression signature, which was validated in multiple independent NSCLC microarray datasets. Functional annotation using protein-protein interaction analyses of these and published cancer stroma-associated gene-expression changes revealed prominent involvement of the focal adhesion and MAPK signaling pathways. Fourteen (30%) of the 46 genes also were differentially expressed in laser-capture-microdissected corresponding primary tumor stroma compared with the matched normal lung. Six of these 14 genes could be induced by TGF-β1 in NF. The results establish the prognostic impact of CAF-associated gene-expression changes in NSCLC patients.integrin α11 | NAViGaTOR | adenocarcinoma | extracellular matrix

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer

Navab

Strumpf

Bandarchi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

321

302

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“…The gene was considered to be overexpressed when the T:N ratio was greater than 2.0 and underexpressed when the ratio was less than 0.5. The criteria for detecting genes were the same as those used in a study by Nakamura et al 18) .…”

Section: Cdna Microarraymentioning

confidence: 99%

Activation of PI3K-AKT Pathway in Oral Epithelial Dysplasia and Early Cancer of Tongue

Watanabe

Sato

Okazaki

et al. 2009

Bull. Tokyo Dent. Coll.

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Increasingly, cancers are being diagnosed at an early stage. Leukoplakia, a precancerous lesion, progresses to cancer in 5-10% of cases. We performed genetic analysis using cDNA microarray and immunohistochemistry in 6 patients, 3 with precancerous lesions and 3 with early tongue cancer, to evaluate the usefulness of these methods in the diagnosis of precancerous lesions and early cancer. Samples of normal epithelium, epithelial dysplasia, and cancer tissues were collected by laser microdissection, RNA was extracted, and the signals converted to numerical values. Immunohistochemical analysis was performed using antibody against phospho AKT (p-AKT), a component of the phosphoinositide 3-kinase (PI3K) signal pathway. Five genes showed a 2 times or greater level of increase in expression in epithelial tissue in comparison with in normal tissue, while 4 genes showed a 2 times or greater increase in early cancer tissues. In cancer tissues and epithelial dysplasia tissues, PI3K class III was expressed at 2.5 times and 11 times the level of that found in normal tissue, respectively. Histochemistry using p-AKT antibody revealed no positive cells in normal tissue. Positive cells were noted in the basal and parabasal cell layers, and partially in the spinous layer of epithelial dysplasia tissues, and in the spinous layer of early cancer tissues. These findings suggest that activation of the PI3K-AKT signal pathway is associated with oral carcinogenesis.

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“…Gene expressions were quantified as the tumor-to-normal fluorescence ratio (T:N ratio). The genes were judged as being overexpressed when the ration was >2.0 and as underexpressed when the ratio was <0.5 (22).…”

Section: Methodsmentioning

confidence: 99%

High expression of GADD-45α and VEGF induced tumor recurrence via upregulation of IL-2 after photodynamic therapy using NPe6

Ohtani

Usuda²,

Ichinose³

et al. 2008

Int J Oncol

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Abstract. NPe6 is a novel second-generation photosensitizer used for photodynamic therapy (PDT). PDT using NPe6 and diode laser (664 nm) induces cell death, inflammatory reactions, immunological responses and damage to the microvasculature. In this study, we evaluated the influence of the immunological responses and of enhanced angiogenesis on the anti-tumor effect of NPe6-PDT using cytokine-overexpressing Lewis lung carcinoma (LLC), LLC-IL-2 cells both in vitro and in vivo. We showed by DNA microarray analysis in vitro that IL-2 and GADD-45α (growth arrest and DNA damage 45 alpha) mRNA expressions were induced by 3 h after NPe6-PDT applied at a dose killing 90% of the cells (LD 90 ). IL-2-overexpressing cells (LLC/IL-2 cells) were resistant to the loss of clonogenicity as compared to the parental LLC cells in vitro. Furthermore, in female C57BL/6 mice, NPe6-PDT produced a cure rate of 66.7% in LLC tumors, whereas the cure rate was only 16.6% in LLC/IL-2 tumors, and overexpression of IL-2 caused failure of NPe6-PDT, with tumor recurrence, in vivo. These results suggest that IL-2 expression may play an unfavorable role in attenuation of the antitumor effect of NPe6-PDT. It has been reported that the expression of vascular endothelial growth factor (VEGF), in particular, may cause tumor recurrence after PDT and exert unfavorable effect in relation to attenuate the anti-tumor activity of PDT. Results of immunohistochemical analysis of LLC/IL-2 tumors have revealed that the expressions of GADD-45α and VEGF are induced in these tumors after PDT, and in particular, 12 h after PDT, the expression levels were much higher as compared with those in the LLC tumors. The results of our studies using in vitro and in vivo models suggest that the cell death caused by PDT was inhibited by induction of GADD-45α expression and that tumor recurrence was promoted by the enhancement of VEGF expression mediated by IL-2 upregulation. Therefore, it is speculated that the use of an IL-2 inhibitor may improve the efficacy of NPe6-PDT.

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cDNA microarray analysis of gene expression in pathologic stage IA nonsmall cell lung carcinomas

Cited by 34 publications

References 28 publications

Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer

Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer

Activation of PI3K-AKT Pathway in Oral Epithelial Dysplasia and Early Cancer of Tongue

High expression of GADD-45α and VEGF induced tumor recurrence via upregulation of IL-2 after photodynamic therapy using NPe6

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