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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

Kaplan-Meier estimates of overall survival according to the mRNA expression levels of (a) RRM2, (b) TS, (c) ERCC1, (d) p53R2, (e) TUBB3, (f) BRCA1, and (g) RRM1 in the overall population.
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Related In: Results  -  Collection


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fig4: Kaplan-Meier estimates of overall survival according to the mRNA expression levels of (a) RRM2, (b) TS, (c) ERCC1, (d) p53R2, (e) TUBB3, (f) BRCA1, and (g) RRM1 in the overall population.

Mentions: When patients were classified into groups based on low and high levels of biomarkers mRNA expression (Table 5), no statistically significant association with OS was detected. K-M plots were similar to those obtained for protein levels except for TUBB3 for which the trend was inverted indicating a longer OS among patients with lower mRNA expression levels (Figures 3-4). Cox multiple regression limited to 64 subjects with complete data (Table 5) identified only pathological TNM as a significant predictor of OS with worse survival associated to stages II (HR = 3.49, 95% CI = 1.30–9.40) and III (HR = 4.39, 95% CI = 1.41–10.68) compared to stage I.


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)

Kaplan-Meier estimates of overall survival according to the mRNA expression levels of (a) RRM2, (b) TS, (c) ERCC1, (d) p53R2, (e) TUBB3, (f) BRCA1, and (g) RRM1 in the overall population.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Kaplan-Meier estimates of overall survival according to the mRNA expression levels of (a) RRM2, (b) TS, (c) ERCC1, (d) p53R2, (e) TUBB3, (f) BRCA1, and (g) RRM1 in the overall population.
Mentions: When patients were classified into groups based on low and high levels of biomarkers mRNA expression (Table 5), no statistically significant association with OS was detected. K-M plots were similar to those obtained for protein levels except for TUBB3 for which the trend was inverted indicating a longer OS among patients with lower mRNA expression levels (Figures 3-4). Cox multiple regression limited to 64 subjects with complete data (Table 5) identified only pathological TNM as a significant predictor of OS with worse survival associated to stages II (HR = 3.49, 95% CI = 1.30–9.40) and III (HR = 4.39, 95% CI = 1.41–10.68) compared to stage I.

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