Gene Expression Profiling and Non–Small-Cell Lung Cancer: Where Are We Now?

Santos, Edgardo S.; Blaya, Marcelo; Raez, Luis E.

doi:10.3816/clc.2009.n.023

Cited by 15 publications

(11 citation statements)

References 46 publications

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“…In recent years, how to improve patients' survival rate by postoperative adjuvant chemotherapy, and how to select the drugs for postoperative adjuvant chemotherapy to make patients obtain more benefits become a focused topic in the field of lung cancer. Studies revealed that a prospective detection to molecular markers is conductive to formulation of individualized therapeutic regimens and enhancement of chemotherapeutic effects (Bartolucci et al, 2009;Santos et al, 2009;Vilmar et al, 2009). For example, the expression levels of excision repair cross complementing 1 (ERCC1), breast cancer susceptibility gene breast cancer 1 (BRCA1) and ribonucleotide reductase M1 (RRM1) are closely associated with the therapeutic effects of chemotherapy drugs and prognosis, and may become the important factors to predict the therapeutic effects so as to conduct individualized treatment (Zhang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

mRNA Expression and Clinical Significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in Postoperative Patients with Non-Small Cell Lung Cancer

Han

Wang²,

Xiao³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: To explore mRNA expression and clinical significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 genes in tumor tissue of postoperative patients with non-small cell lung cancer (NSCLC). Materials and Methods: Sixty NSCLC patients undergoing radical operation in our hospital from Nov., 2011 to Jun., 2012 were selected. Plasmid standards of ERCC1, BRCA1, RRM1, TYMS and TUBB3 were established and standard curves were prepared by SYBR fluorescent real-time quantitative PCR analysis. Samples from tumor centers were taken to detect mRNA expression of ERCC1, BRCA1, RRM1, TYMS and TUBB3 genes in cancerous tissue during operation. The total mRNA expression quantities were compared according to different clinical characteristics. Results: The total expression quantities of 5 genotypes from high to low were ERCC1>RRM1>TUBB3>TYMS>BRCA1 in turn. By pairwise comparisons, other differences showed statistical significance (p<0.05 or p<0.01) except for TYMS and TUBB3 (p>0.05); the low expression rates from high to low were ERCC1>TYMS>TUBB3>TUBB3>RRM1>BRCA1 in turn. The expression quantities of BRCA1, RRM1 and TYMS in males, smokers and patients without adenocarcinoma were all significantly higher than that in females, non-smokers and patients with adenocarcinoma, and significant differences were present (p<0.05 or p<0.01). In terms of pathological staging, the expression quantities of BRCA1, RRM1 and TYMS in phases Ⅱa~Ⅱb and Ⅲa~Ⅲb had a tendency to be greater than in phases Ⅰ and Ⅳ. Conclusions: Resistance to chemotherapy and sensitivity to targeted therapy differ among patients with NSCLC. Differences in gene expression in different individuals were also revealed. Only according to personalized detection results can individualized therapeutic regimens be worked out, which is a new direction for oncotherapy.

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Section: Introductionmentioning

confidence: 99%

mRNA Expression and Clinical Significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in Postoperative Patients with Non-Small Cell Lung Cancer

Han

Wang²,

Xiao³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Metastasis is the most frequent reason for early-stage NSCLC-related death, and receptor tyrosine kinases (RTK) play an important role in this process (3,4). The role of epidermal growth factor receptor and its family members ERBB2/ Her2 Neu and ERBB3 for a metastasis phenotype are well established.…”

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confidence: 99%

The EPHB6 Receptor Tyrosine Kinase Is a Metastasis Suppressor That Is Frequently Silenced by Promoter DNA Hypermethylation in Non–Small Cell Lung Cancer

Bulk

et al. 2010

Clinical Cancer Research

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Purpose: Loss of EPHB6 receptor tyrosine kinase expression in early-stage non-small cell lung carcinoma (NSCLC) is associated with the subsequent development of distant metastasis. Here, we analyzed the regulation and function of EPHB6 in lung cancer metastasis.Experimental Design: The expression levels of EPHB6 were compared among normal lung tissue (n = 9), NSCLC without metastasis (n = 39), and NSCLC with metastasis (n = 39) according to the history of the patients. In addition, EPHB6 expression levels of matched tumor-normal pairs from 24 NSCLC patients were analyzed. The promoter DNA methylation status and its association with the expression levels of EPHB6 were determined among 14 pairs of tumor-normal samples. Metastatic potential of EPHB6 was assessed in vitro and in vivo in a metastasis mouse model. Overexpression and RNA interference (RNAi) approaches were used for analysis of the biological functions of EPHB6.Results: EPHB6 mRNA and protein levels were significantly reduced in NSCLC tumors compared with matched normal lung tissue. Decreased EPHB6 expression levels were associated with an increased risk for metastasis development in NSCLC patients. Loss of expression correlated with EPHB6 hypermethylation. EPHB6 expression was induced by 5-aza-2'-deoxycytidine treatment in an NSCLC cell line. Restoration of EPHB6 expression in lung adenocarcinoma cells increased adhesion and decreased migration. Reexpression of EPHB6 in lung cancer cells almost entirely abolished metastasis formation in non obese diabetic (NOD)/severe combined immunodeficient mice.Conclusions: Taken together, these analyses show that EPHB6 is a metastasis inhibitory gene that is frequently silenced by hypermethylation of its promoter in NSCLC. Clin Cancer Res; 16(8); 2275-83. ©2010 AACR.Lung cancer is a leading cause of cancer-related death, with non-small cell lung carcinoma (NSCLC) as the most frequent histologic subtype (1, 2). Metastasis is the most frequent reason for early-stage NSCLC-related death, and receptor tyrosine kinases (RTK) play an important role in this process (3, 4). The role of epidermal growth factor receptor and its family members ERBB2/ Her2 Neu and ERBB3 for a metastasis phenotype are well established. RTKs such as the epidermal growth factor receptor family are therefore attractive targets for improved molecular therapy approaches in cancers (3, 5). We have recently identified human RTKs whose expression is associated with metastasis development in early-stage NSCLC (6). Expression of several RTKs was associated with an increased frequency of metastasis development. Increased expression of RTKs, for example, due to gene amplification, is clearly associated with metastasis. The role of a loss of expression of other types of RTKs in metastasis has not been established. In our expression analysis, EPHB6 was one of two RTKs associated with a high risk for NSCLC metastasis when its expression was lost (6).Erythropoietin-producing hepatocyte kinase (EPH) receptors form the largest known subfamily of RTKs, an...

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“…Lung cancer, the most common cause of cancer-related death among both men and women, may be classified as either small cell or non-small cell[1] [2]. Non-small cell lung cancer (NSCLC) is more common, accounting for approximately 85% of lung cancer cases[3].…”

Section: Clinical Scenariomentioning

confidence: 99%

ERCC1 Expression Analysis to Guide Therapy in Non-Small Cell Lung Cancer

Allingham-Hawkins¹,

Lea²,

Levine³

2010

PLoS Curr

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Worldwide, lung cancer accounts for approximately 1 million deaths each year, making it the most common cause of cancer-related mortality. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases and is often associated with a relatively poor prognosis. The majority of NSCLC patients present with advanced disease and have an average 5-year survival rate of 5%. Currently, the standard of care for NSCLC includes treatment with a platinum-based chemotherapy regimen. However, not all patients benefit equally from such treatment. Therefore, recent pharmacogenomic studies have been performed in order to identify specific biomarkers that may allow for patient-tailored treatment strategies. One such biomarker is expression of the excision repair cross-complementation group 1 protein, ERCC1.

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Gene Expression Profiling and Non–Small-Cell Lung Cancer: Where Are We Now?

Cited by 15 publications

References 46 publications

mRNA Expression and Clinical Significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in Postoperative Patients with Non-Small Cell Lung Cancer

mRNA Expression and Clinical Significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in Postoperative Patients with Non-Small Cell Lung Cancer

The EPHB6 Receptor Tyrosine Kinase Is a Metastasis Suppressor That Is Frequently Silenced by Promoter DNA Hypermethylation in Non–Small Cell Lung Cancer

ERCC1 Expression Analysis to Guide Therapy in Non-Small Cell Lung Cancer

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