Non-small cell lung cancer exhibits Transcript overexpression of Genes associated with homologous recombination and DNA replication pathways

Silvia Saviozzi*, Paolo Ceppi, Silvia Novello, Paolo Ghio, Marco Lo Iacono, Piero Borasio, Alberto Cambieri, Marco Volante, Mauro Papotti, Raffaele A. Calogero, Giorgio V. Scagliotti

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Genes involved in DNA repair and replication have been recently investigated as predictive markers of response to chemotherapy in non-small cell lung cancer (NSCLC). However, few data on the expression of these genes in tumor compared with corresponding normal lung are available. The aim of this study was to evaluate differential mRNA levels of 22 DNA repair genes of five different DNA repair pathways: direct, base excision, nucleotide excision (NER), double-strand break (DSBR), and postreplicative repair. In addition, six genes involved in DNA replication (REP) and three telomere maintenance genes were investigated. Total RNAs extracted from fresh-frozen tumors and corresponding normal tissues of 50 consecutive chemo-naïve resected NSCLC patients were analyzed. Transcript levels were quantified by real-time PCR. A significant overexpression was detected in 20 of 30 (67%) genes, mostly belonging to DSBR pathways, whereas others (XPA, XPC, and UBE2N; 10%) were significantly underex-pressed. For 7 of 30 (23%) genes, mostly belonging to NER pathway, no significant difference between paired tumor and normal samples was observed. Transcript overexpression of DSBR and REP genes was significantly higher in poorly differentiated carcinomas and DSBR levels were higher in men compared with women. The transcriptional overexpression of four genes (XRCCS, TOP3B, TYMS, and UNG) showed significant correlation with a shorter patients' outcome at the univariate, whereas only stage of disease appeared as an independent factor affecting prognosis, as assessed by multivariate analysis. In conclusion, genes belonging to DNA repair/replication pathways are overexpressed in NSCLC and are associated with a more aggressive phenotype.

OriginalsprogEngelsk
TidsskriftCancer research
Vol/bind69
Udgave nummer8
Sider (fra-til)3390-3396
Antal sider7
ISSN0008-5472
DOI
StatusUdgivet - 15. apr. 2009

Fingeraftryk

Neoplasms
Telomere
Real-Time Polymerase Chain Reaction
Multivariate Analysis
Maintenance
RNA
Lung
Messenger RNA

Citer dette

Saviozzi, Silvia ; Ceppi, Paolo ; Novello, Silvia ; Ghio, Paolo ; Iacono, Marco Lo ; Borasio, Piero ; Cambieri, Alberto ; Volante, Marco ; Papotti, Mauro ; Calogero, Raffaele A. ; Scagliotti, Giorgio V. / Non-small cell lung cancer exhibits Transcript overexpression of Genes associated with homologous recombination and DNA replication pathways. I: Cancer research. 2009 ; Bind 69, Nr. 8. s. 3390-3396.
@article{a07f1954736b49b081dc0cb760a27e41,
title = "Non-small cell lung cancer exhibits Transcript overexpression of Genes associated with homologous recombination and DNA replication pathways",
abstract = "Genes involved in DNA repair and replication have been recently investigated as predictive markers of response to chemotherapy in non-small cell lung cancer (NSCLC). However, few data on the expression of these genes in tumor compared with corresponding normal lung are available. The aim of this study was to evaluate differential mRNA levels of 22 DNA repair genes of five different DNA repair pathways: direct, base excision, nucleotide excision (NER), double-strand break (DSBR), and postreplicative repair. In addition, six genes involved in DNA replication (REP) and three telomere maintenance genes were investigated. Total RNAs extracted from fresh-frozen tumors and corresponding normal tissues of 50 consecutive chemo-na{\"i}ve resected NSCLC patients were analyzed. Transcript levels were quantified by real-time PCR. A significant overexpression was detected in 20 of 30 (67{\%}) genes, mostly belonging to DSBR pathways, whereas others (XPA, XPC, and UBE2N; 10{\%}) were significantly underex-pressed. For 7 of 30 (23{\%}) genes, mostly belonging to NER pathway, no significant difference between paired tumor and normal samples was observed. Transcript overexpression of DSBR and REP genes was significantly higher in poorly differentiated carcinomas and DSBR levels were higher in men compared with women. The transcriptional overexpression of four genes (XRCCS, TOP3B, TYMS, and UNG) showed significant correlation with a shorter patients' outcome at the univariate, whereas only stage of disease appeared as an independent factor affecting prognosis, as assessed by multivariate analysis. In conclusion, genes belonging to DNA repair/replication pathways are overexpressed in NSCLC and are associated with a more aggressive phenotype.",
author = "Silvia Saviozzi and Paolo Ceppi and Silvia Novello and Paolo Ghio and Iacono, {Marco Lo} and Piero Borasio and Alberto Cambieri and Marco Volante and Mauro Papotti and Calogero, {Raffaele A.} and Scagliotti, {Giorgio V.}",
year = "2009",
month = "4",
day = "15",
doi = "10.1158/0008-5472.CAN-08-2981",
language = "English",
volume = "69",
pages = "3390--3396",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research (A A C R)",
number = "8",

}

Saviozzi, S, Ceppi, P, Novello, S, Ghio, P, Iacono, ML, Borasio, P, Cambieri, A, Volante, M, Papotti, M, Calogero, RA & Scagliotti, GV 2009, 'Non-small cell lung cancer exhibits Transcript overexpression of Genes associated with homologous recombination and DNA replication pathways', Cancer research, bind 69, nr. 8, s. 3390-3396. https://doi.org/10.1158/0008-5472.CAN-08-2981

Non-small cell lung cancer exhibits Transcript overexpression of Genes associated with homologous recombination and DNA replication pathways. / Saviozzi, Silvia; Ceppi, Paolo; Novello, Silvia; Ghio, Paolo; Iacono, Marco Lo; Borasio, Piero; Cambieri, Alberto; Volante, Marco; Papotti, Mauro; Calogero, Raffaele A.; Scagliotti, Giorgio V.

I: Cancer research, Bind 69, Nr. 8, 15.04.2009, s. 3390-3396.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Non-small cell lung cancer exhibits Transcript overexpression of Genes associated with homologous recombination and DNA replication pathways

AU - Saviozzi, Silvia

AU - Ceppi, Paolo

AU - Novello, Silvia

AU - Ghio, Paolo

AU - Iacono, Marco Lo

AU - Borasio, Piero

AU - Cambieri, Alberto

AU - Volante, Marco

AU - Papotti, Mauro

AU - Calogero, Raffaele A.

AU - Scagliotti, Giorgio V.

PY - 2009/4/15

Y1 - 2009/4/15

N2 - Genes involved in DNA repair and replication have been recently investigated as predictive markers of response to chemotherapy in non-small cell lung cancer (NSCLC). However, few data on the expression of these genes in tumor compared with corresponding normal lung are available. The aim of this study was to evaluate differential mRNA levels of 22 DNA repair genes of five different DNA repair pathways: direct, base excision, nucleotide excision (NER), double-strand break (DSBR), and postreplicative repair. In addition, six genes involved in DNA replication (REP) and three telomere maintenance genes were investigated. Total RNAs extracted from fresh-frozen tumors and corresponding normal tissues of 50 consecutive chemo-naïve resected NSCLC patients were analyzed. Transcript levels were quantified by real-time PCR. A significant overexpression was detected in 20 of 30 (67%) genes, mostly belonging to DSBR pathways, whereas others (XPA, XPC, and UBE2N; 10%) were significantly underex-pressed. For 7 of 30 (23%) genes, mostly belonging to NER pathway, no significant difference between paired tumor and normal samples was observed. Transcript overexpression of DSBR and REP genes was significantly higher in poorly differentiated carcinomas and DSBR levels were higher in men compared with women. The transcriptional overexpression of four genes (XRCCS, TOP3B, TYMS, and UNG) showed significant correlation with a shorter patients' outcome at the univariate, whereas only stage of disease appeared as an independent factor affecting prognosis, as assessed by multivariate analysis. In conclusion, genes belonging to DNA repair/replication pathways are overexpressed in NSCLC and are associated with a more aggressive phenotype.

AB - Genes involved in DNA repair and replication have been recently investigated as predictive markers of response to chemotherapy in non-small cell lung cancer (NSCLC). However, few data on the expression of these genes in tumor compared with corresponding normal lung are available. The aim of this study was to evaluate differential mRNA levels of 22 DNA repair genes of five different DNA repair pathways: direct, base excision, nucleotide excision (NER), double-strand break (DSBR), and postreplicative repair. In addition, six genes involved in DNA replication (REP) and three telomere maintenance genes were investigated. Total RNAs extracted from fresh-frozen tumors and corresponding normal tissues of 50 consecutive chemo-naïve resected NSCLC patients were analyzed. Transcript levels were quantified by real-time PCR. A significant overexpression was detected in 20 of 30 (67%) genes, mostly belonging to DSBR pathways, whereas others (XPA, XPC, and UBE2N; 10%) were significantly underex-pressed. For 7 of 30 (23%) genes, mostly belonging to NER pathway, no significant difference between paired tumor and normal samples was observed. Transcript overexpression of DSBR and REP genes was significantly higher in poorly differentiated carcinomas and DSBR levels were higher in men compared with women. The transcriptional overexpression of four genes (XRCCS, TOP3B, TYMS, and UNG) showed significant correlation with a shorter patients' outcome at the univariate, whereas only stage of disease appeared as an independent factor affecting prognosis, as assessed by multivariate analysis. In conclusion, genes belonging to DNA repair/replication pathways are overexpressed in NSCLC and are associated with a more aggressive phenotype.

UR - http://www.scopus.com/inward/record.url?scp=65949124261&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-08-2981

DO - 10.1158/0008-5472.CAN-08-2981

M3 - Journal article

VL - 69

SP - 3390

EP - 3396

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 8

ER -