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Expression of Ribonucleotide Reductase Subunit-2 and Thymidylate Synthase Correlates with Poor Prognosis in Patients with Resected Stages I-III Non-Small Cell Lung Cancer.

Grossi F, Dal Bello MG, Salvi S, Puzone R, Pfeffer U, Fontana V, Alama A, Rijavec E, Barletta G, Genova C, Sini C, Ratto GB, Taviani M, Truini M, Merlo DF - Dis. Markers (2015)

Bottom Line: Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS).Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours.For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels.

View Article: PubMed Central - PubMed

Affiliation: Lung Cancer Unit, IRCCS A.O.U San Martino IST-Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy.

ABSTRACT

Unlabelled: Biomarkers can help to identify patients with early-stages or locally advanced non-small cell lung cancer (NSCLC) who have high risk of relapse and poor prognosis. To correlate the expression of seven biomarkers involved in DNA synthesis and repair and in cell division with clinical outcome, we consecutively collected 82 tumour tissues from radically resected NSCLC patients. The following biomarkers were investigated using IHC and q

Rt-pcr: excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2), subunit p53R2, thymidylate synthase (TS), and class III beta-tubulin (TUBB3). Gene expression levels were also validated in an available NSCLC microarray dataset. Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS). Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours. For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. The NSCLC microarray dataset showed RRM2 and TS as biomarkers significantly associated with OS. This study suggests that high expression levels of RRM2 and TS might be negative prognostic factors for resected NSCLC patients.

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Related in: MedlinePlus

Representative results of IHC staining of NSCLC tumour specimens for RRM2, RRM1, and p53R2. (a) Negative expression of RRM2 (final score 0), (b) high expression of RRM2: cytoplasmic staining (final score 3); (c) negative expression of RRM1 (final score 0), (d) high expression of RRM1: cytoplasmic staining (final score 2); and (e) negative expression of p53R2 (final score 0), (f) high expression of p53R2: nuclear staining (final score 3).
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fig2: Representative results of IHC staining of NSCLC tumour specimens for RRM2, RRM1, and p53R2. (a) Negative expression of RRM2 (final score 0), (b) high expression of RRM2: cytoplasmic staining (final score 3); (c) negative expression of RRM1 (final score 0), (d) high expression of RRM1: cytoplasmic staining (final score 2); and (e) negative expression of p53R2 (final score 0), (f) high expression of p53R2: nuclear staining (final score 3).

Mentions: Representative results of immunohistochemical staining of NSCLC specimens are provided in Figures 1-2.


Expression of Ribonucleotide Reductase Subunit-2 and Thymidylate Synthase Correlates with Poor Prognosis in Patients with Resected Stages I-III Non-Small Cell Lung Cancer.

Grossi F, Dal Bello MG, Salvi S, Puzone R, Pfeffer U, Fontana V, Alama A, Rijavec E, Barletta G, Genova C, Sini C, Ratto GB, Taviani M, Truini M, Merlo DF - Dis. Markers (2015)

Representative results of IHC staining of NSCLC tumour specimens for RRM2, RRM1, and p53R2. (a) Negative expression of RRM2 (final score 0), (b) high expression of RRM2: cytoplasmic staining (final score 3); (c) negative expression of RRM1 (final score 0), (d) high expression of RRM1: cytoplasmic staining (final score 2); and (e) negative expression of p53R2 (final score 0), (f) high expression of p53R2: nuclear staining (final score 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4664813&req=5

fig2: Representative results of IHC staining of NSCLC tumour specimens for RRM2, RRM1, and p53R2. (a) Negative expression of RRM2 (final score 0), (b) high expression of RRM2: cytoplasmic staining (final score 3); (c) negative expression of RRM1 (final score 0), (d) high expression of RRM1: cytoplasmic staining (final score 2); and (e) negative expression of p53R2 (final score 0), (f) high expression of p53R2: nuclear staining (final score 3).
Mentions: Representative results of immunohistochemical staining of NSCLC specimens are provided in Figures 1-2.

Bottom Line: Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS).Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours.For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels.

View Article: PubMed Central - PubMed

Affiliation: Lung Cancer Unit, IRCCS A.O.U San Martino IST-Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy.

ABSTRACT

Unlabelled: Biomarkers can help to identify patients with early-stages or locally advanced non-small cell lung cancer (NSCLC) who have high risk of relapse and poor prognosis. To correlate the expression of seven biomarkers involved in DNA synthesis and repair and in cell division with clinical outcome, we consecutively collected 82 tumour tissues from radically resected NSCLC patients. The following biomarkers were investigated using IHC and q

Rt-pcr: excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2), subunit p53R2, thymidylate synthase (TS), and class III beta-tubulin (TUBB3). Gene expression levels were also validated in an available NSCLC microarray dataset. Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS). Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours. For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. The NSCLC microarray dataset showed RRM2 and TS as biomarkers significantly associated with OS. This study suggests that high expression levels of RRM2 and TS might be negative prognostic factors for resected NSCLC patients.

Show MeSH
Related in: MedlinePlus