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Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer

The aim of our study was to look for alternative predictive biomarkers for breast cancer management in limited resource setup. A comprehensive analysis of circulating cell-free DNA (CCFD) in serum at baseline was performed to assess its prognostic potential. Quantitative polymerase chain reaction (q...

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Autores principales: Iqbal, Sobuhi, Vishnubhatla, Sreenivas, Raina, Vinod, Sharma, Surabhi, Gogia, Ajay, Deo, Suryanarayana S V, Mathur, Sandeep, Shukla, Nutan Kumar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469592/
https://www.ncbi.nlm.nih.gov/pubmed/26090312
http://dx.doi.org/10.1186/s40064-015-1071-y
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author Iqbal, Sobuhi
Vishnubhatla, Sreenivas
Raina, Vinod
Sharma, Surabhi
Gogia, Ajay
Deo, Suryanarayana S V
Mathur, Sandeep
Shukla, Nutan Kumar
author_facet Iqbal, Sobuhi
Vishnubhatla, Sreenivas
Raina, Vinod
Sharma, Surabhi
Gogia, Ajay
Deo, Suryanarayana S V
Mathur, Sandeep
Shukla, Nutan Kumar
author_sort Iqbal, Sobuhi
collection PubMed
description The aim of our study was to look for alternative predictive biomarkers for breast cancer management in limited resource setup. A comprehensive analysis of circulating cell-free DNA (CCFD) in serum at baseline was performed to assess its prognostic potential. Quantitative polymerase chain reaction (qPCR) of ALU sequences using ALU115 and ALU247 primers was carried out in patients (N: baseline 148, postoperative 47) and 51 healthy controls. Mean serum DNA integrity, levels of ALU 247 and levels of ALU 115 were significantly higher in patients than in healthy females. No significant differences were observed in the levels ALU 247 and ALU 115 between stage IV and earlier stages of the disease. The DNA integrity was significantly higher in stage IV than earlier stages. A significant decrease in DNA integrity was observed after surgery (pre: 0.55 ± 0.23 vs post: 0.43 ± 0.30; P = 0.002) while no such change could be observed for ALU 247 and ALU 115. Baseline DNA integrity was significantly higher in relapsed patients than in patients who were free of disease (P = 0.005). Higher baseline DNA integrity was also indicated, though statistically not significant, in patients who died (P = 0.14). In contrast, ALU 247 and ALU 115 levels were decreased in died patients as compared to survivors (24.8 ± 34.80 vs 73.5 ± 170.83, P = 0.02 for ALU 247 and 41.0 ± 47.99 vs 159.5 ± 299.54, P = 0.005 for ALU 115). Baseline levels of ALU 115 and ALU 247 were lower in relapsed patients, though statistically not significant. In univariate analysis, the only clinic-pathological parameter associated with disease prognosis was tumor size. The hazards of 5-year overall mortality was 3.60 (95 % CI: 1.03 12.53, P = 0.03) among patients with lower baseline serum levels of CCFD (ALU 247 < 21 and ALU 115 < 41). Similarly the 4 year hazards for recurrence was 2.30 (95 % CI: 0.96 5.52, P = 0.05) among patients with higher DNA integrity. Baseline serum levels of CCFD and its integrity were found to be potential prognostic biomarkers in patients of primary breast cancer at our centre. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1071-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-44695922015-06-18 Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer Iqbal, Sobuhi Vishnubhatla, Sreenivas Raina, Vinod Sharma, Surabhi Gogia, Ajay Deo, Suryanarayana S V Mathur, Sandeep Shukla, Nutan Kumar Springerplus Research The aim of our study was to look for alternative predictive biomarkers for breast cancer management in limited resource setup. A comprehensive analysis of circulating cell-free DNA (CCFD) in serum at baseline was performed to assess its prognostic potential. Quantitative polymerase chain reaction (qPCR) of ALU sequences using ALU115 and ALU247 primers was carried out in patients (N: baseline 148, postoperative 47) and 51 healthy controls. Mean serum DNA integrity, levels of ALU 247 and levels of ALU 115 were significantly higher in patients than in healthy females. No significant differences were observed in the levels ALU 247 and ALU 115 between stage IV and earlier stages of the disease. The DNA integrity was significantly higher in stage IV than earlier stages. A significant decrease in DNA integrity was observed after surgery (pre: 0.55 ± 0.23 vs post: 0.43 ± 0.30; P = 0.002) while no such change could be observed for ALU 247 and ALU 115. Baseline DNA integrity was significantly higher in relapsed patients than in patients who were free of disease (P = 0.005). Higher baseline DNA integrity was also indicated, though statistically not significant, in patients who died (P = 0.14). In contrast, ALU 247 and ALU 115 levels were decreased in died patients as compared to survivors (24.8 ± 34.80 vs 73.5 ± 170.83, P = 0.02 for ALU 247 and 41.0 ± 47.99 vs 159.5 ± 299.54, P = 0.005 for ALU 115). Baseline levels of ALU 115 and ALU 247 were lower in relapsed patients, though statistically not significant. In univariate analysis, the only clinic-pathological parameter associated with disease prognosis was tumor size. The hazards of 5-year overall mortality was 3.60 (95 % CI: 1.03 12.53, P = 0.03) among patients with lower baseline serum levels of CCFD (ALU 247 < 21 and ALU 115 < 41). Similarly the 4 year hazards for recurrence was 2.30 (95 % CI: 0.96 5.52, P = 0.05) among patients with higher DNA integrity. Baseline serum levels of CCFD and its integrity were found to be potential prognostic biomarkers in patients of primary breast cancer at our centre. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1071-y) contains supplementary material, which is available to authorized users. Springer International Publishing 2015-06-17 /pmc/articles/PMC4469592/ /pubmed/26090312 http://dx.doi.org/10.1186/s40064-015-1071-y Text en © Iqbal et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Research
Iqbal, Sobuhi
Vishnubhatla, Sreenivas
Raina, Vinod
Sharma, Surabhi
Gogia, Ajay
Deo, Suryanarayana S V
Mathur, Sandeep
Shukla, Nutan Kumar
Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer
title Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer
title_full Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer
title_fullStr Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer
title_full_unstemmed Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer
title_short Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer
title_sort circulating cell-free dna and its integrity as a prognostic marker for breast cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469592/
https://www.ncbi.nlm.nih.gov/pubmed/26090312
http://dx.doi.org/10.1186/s40064-015-1071-y
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