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ALU repeat as potential molecular marker in the detection and prognosis of different cancer types: A systematic review

Authors:
Semaa A. Shaban at Tikrit University
Semaa A. Shaban
Aya M. Al-Rahim at Al-Nahrain University
Aya M. Al-Rahim
Ahmed AbdulJabbar Suleiman at University of Anbar, College of Science
Ahmed AbdulJabbar Suleiman
  • University of Anbar, College of Science
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Abstract

Cancer is a major health issue worldwide. cfDNA integrity has been reported as a potential diagnostic molecular marker for different types of cancer, identifying the importance of liquid biopsy. The aim of this review was to evaluate the prognostic and
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ALU repeat as potential molecular marker in the detection and prognosis of different cancer types: A systematic review
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ALU repeat as potential molecular marker in
the detection and prognosis of different cancer types:
A systematic review
Authors: Semaa A. Shaban, Aya M. Al‑Rahim, Ahmed Abduljabbar Suleiman
View Affiliations
Published online on: February 21, 2022  https://doi.org/10.3892/mco.2022.2519
Article Number: 86
Copyright: © Shaban et al. This is an open access article distributed under the terms of
Creative Commons Attribution License.
Metrics: Total Views: 131 (Spandidos Publications: 131 | PMC Statistics: 0 )
Total PDF Downloads: 86 (Spandidos Publications: 86 | PMC Statistics: 0 )
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Abstract
Cancer is a major health issue worldwide. cfDNA integrity has been reported as a
potential diagnostic molecular marker for different types of cancer, identifying the
importance of liquid biopsy. The aim of this review was to evaluate the prognostic and
diagnostic performance of
Arthrobacterluteus
(ALU) repeat in tumor. Following a
thorough review of the literature published from January, 2000 to September 2021, 36
studies were included. All of the study descriptions were analyzed. According to several
studies, there were increased concentrations of ALU repetitive elements in cancer
patients, while these concentrations were decreased in control, benign, different cancer
stage, and other diseases. The total ALU (115 and 247) sequence levels are potential
biomarkers for the purpose of investigations and cancer prognosis.
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Volume 16 Issue 4
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... As a method of detection and prognosis for various types of cancer, circulating tumor cells, circulating DNA, and microRNAs have been investigated. 10 The majority of cell free plasma DNA in healthy individuals is composed of DNA repeat sequences that include long and short interspersed nucleotide elements. 11 Cell free DNA (cf-DNA), are short fragments of nucleic acids that are present in the circulation. ...
... 13 Multiple studies also have indicated elevated levels of cf-DNA in breast cancer, [14][15][16] and several other malignancies as colorectal cancer, lung cancer, testicular cancer, prostate cancer, ovarian cancer and other solid tumors. 10 Many gene sequences such as the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene, ß-globin-gene, human telomerase reverse transcriptase (hTERT), LINE1 (long interspersed nucleotide elements) were studied as biomarkers in breast cancer. 17 The Arthrobacter luteus (ALU) sequences were chosen because they are the most common and active repeated elements in the human genome. ...
The role of circulating cell-free DNA and its integrity as a biomarker for diagnosis of breast cancer using ALU (247/115) bP sequences
Article
  • Jul 2023
Diagnosis of breast cancer by using sensitive and specific biomarkers is necessary. Cell- free DNA (cf-DNA) is a candidate biomarker in various cancers. Contrasting, shorted uniformed DNA released from apoptotic non-diseased cells, DNA released from malignant cells varies in size. DNA integrity is a ratio between 247 and 115 bp. This study aimed to evaluate the diagnostic values of cf-DNA using ALU -247 and ALU- 115 and DNA integrity in peripheral blood of breast cancer patients as a noninvasive marker. Also, to determine correlations between ALU-247 and ALU-115, DNA integrity, cancer antigen (CA )15-3 and carcinoembryonic antigen (CEA) with each other in breast cancer patients and in different stages of breast cancer. This study included 100 females, divided into 3 groups. The first group consisted of 20 apparently healthy females as the control group. The second group included 20 patients with benign breast lesions. The third group included 60 patients with breast cancer. Serum levels of both ALU-247 and ALU-115 as well as cf-DNA integrity were statistically significant higher in breast cancer patients as compared to the control group (p=0.018, p < 0.001 and p=0.009 respectively). Compared to the control group, ALU-247 had the best diagnostic sensitivity for diagnosis of breast cancer (86.78%) with 75% specificity with area under the curve of 0.848. We concluded that measuring ALU-247, ALU-115 and DNA integrity in peripheral blood would be a promising novel approach for diagnosis and early detection of breast cancer.
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... The advent of real-time quantitative PCR (q-PCR) has enabled a quick and cost-effective method of detecting the target biomarker ALU elements in ccfDNA from the serum or plasma of cancer patients. The ratio between long and short ccfDNA fragments (DI) has been used as a potential diagnostic marker in multiple cancer types including breast cancer [10,[12][13][14]. In this study, we have used liquid biopsy to evaluate prognosis and to monitor disease progression in breast cancer patients by assessing the small and large ALU repetitive element levels. ...
Estimation of ALU Repetitive Elements in Plasma as a Cost-Effective Liquid Biopsy Tool for Disease Prognosis in Breast Cancer
Article
Full-text available
  • Feb 2023
Background: Liquid biopsy is widely recognized as an efficient diagnostic method in oncology for disease detection and monitoring. Though the examination of circulating tumor cells (CTC) is mostly implemented for the assessment of genomic aberrations, the need of complex methodologies for their detection has impeded its acceptance in low-resource settings. We evaluated cell-free DNA (cfDNA) as a liquid biopsy tool and investigated its utility in breast cancer patients. Methods: Total cell-free DNA was extracted from the plasma of breast cancer patients (n = 167) with a median follow-up of more than 5 years, at various stages of the disease. Quantitative PCR was performed to estimate the copy numbers of two fractions of ALU repetitive elements (ALU 115 and ALU 247), and DNA integrity (DI) was calculated as the ratio of ALU 247/115. Mutations in TP53 and PIK3CA in the cfDNA were estimated by next-gen sequencing (NGS) in a subset of samples. Associations of the levels of both the ALU fragments with various clinico-pathological factors and disease-free survival at various stages were examined. Nomogram models were constructed with clinical variables and ALU 247 levels to predict disease-free survival and the best performing model was evaluated by decision curve analysis. Results: DI and ALU 247 levels were significantly lower (p < 0.0001) in the post-operative plasma when compared to their pre-surgery levels. DI and ALU 247 were found to be significantly higher in patients with metastasis (p < 0.05). Patients with higher levels of ALU 247 in their post-operative plasma had significant poor disease-free survival (p = 0.005). Higher levels of ALU 247 in the circulation also correlated with low tumor-infiltrating lymphocytes (TIL) within their primary tumors in the ER-negative breast cancer subtype (p = 0.01). Cox proportional hazard analysis confirmed ALU 247 as an independent variable of disease-free survival both in univariate and multivariate analysis [HR 1.3 (95% CI 1.047 to 1.613, p = 0.017)]. The nomogram model showed that the addition of ALU 247 with other variables significantly improved (C-index 0.823) the predictive ability of the model. Conclusion: Our results confirm the utility of cfDNA as an evolving liquid biopsy tool for molecular analysis. Evaluation of larger fragments of cfDNA estimated through ALU 247 can provide vital information concurrent with the pathological process of disease evolution in breast cancer and warrants expansion to other cancer types.
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... The advent of real-time quantitative PCR (q-PCR) has enabled a quick and cost-effective method of detecting the target biomarker ALU elements in ccfDNA from the serum or plasma of cancer patients. The ratio between the long and short ccfDNA fragments (DI) have been used as a potential diagnostic marker in multiple cancer types including breast cancer (4,(6)(7)(8). In this study, we have used liquid biopsy to evaluate prognosis and monitor disease progression in breast cancer patients by assessing the small and large ALU repetitive element levels. ...
Estimation of ALU Repetitive Element in Plasma as a Cost-Effective Liquid Biopsy Tool for Disease Prognosis in Breast Cancer
Preprint
  • Dec 2022
Background: Liquid biopsy is widely recognised as an efficient diagnostic method in oncology for disease detection and monitoring. Though examination of circulating tumor cell (CTC) is mostly implemented for assessment of genomic aberrations, need of complex methodologies for their detection has impeded its acceptance in low resource settings. We evaluated the cell free DNA (cfDNA) as a liquid biopsy tool and investigated its utility in breast cancer patients. Methods: Total cell free DNA was extracted from plasma of breast cancer patients (n=167) with median follow up of more than 5 years, at various stages of the disease. Quantitative PCR was performed to estimate the copy numbers of two fractions of ALU repetitive elements (ALU 115 and ALU 247) and DNA Integrity (DI) was calculated as the ratio of ALU 247/115. Mutations in TP53 and PIK3CA in the cfDNA was estimated by next-gen sequencing (NGS) in a subset of samples. Association of the levels of both the ALU fragments with various clinico-pathological factors and disease-free survival at various stages were examined. Nomogram models were constructed with clinical variables and ALU 247 levels to predict disease-free survival and best performing model was evaluated by decision curve analysis. Results: DI and ALU 247 levels were significantly lower (p<0.0001) in the post-operative plasma when compared to their pre-surgery levels. DI and ALU 247 were found to be significantly higher in patients with metastasis (p<0.05). Patients with higher levels of ALU 247 in their post-operative plasma had significantly poor disease-free survival (p=0.005). Higher level of ALU 247 in circulation also correlated with low tumor-infiltrating lymphocytes (TIL) within their primary tumors in the ER-negative breast cancer subtype (p=0.01). Cox proportional hazard analysis confirmed ALU 247 as an independent variable of disease-free survival both in univariate and multivariate analysis [HR 1.3 (95% CI 1.047 to 1.613, p= 0.017)]. Nomogram model showed addition of ALU 247 with other variables significantly improved (C-index-0.823) the predictive ability of the model. Conclusion: Our results confirm the utility of cfDNA as an evolving liquid biopsy tool for molecular analysis. Evaluation of larger fragment of cfDNA estimated through ALU 247 can provide vital information concurrent with the pathological process of disease evolution in breast cancer and warrants expansion to other cancer types.
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