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

Shaban, Semaa A.; Al-Rahim, Aya M.; Suleiman, Ahmed AbdulJabbar

doi:10.3892/mco.2022.2519

Cited by 6 publications

(8 citation statements)

References 59 publications

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“…Additionally, such approaches are frequently limited to low sample volume and are hard to automate [ 13 ]. Other frequently cited CTC detection approaches include Prostate-Specific Membrane Antigen( PSMA)-specific cell surface labeling [ 14 ] or Alu element sequencing [ 15 ]. Though these methods have undoubtedly proved useful and accurate in the past, such time-intensive and laborious approaches are much better suited for downstream validation testing of any promising preliminary results yielded using our swift and simple approach.…”

Section: Discussionmentioning

confidence: 99%

Multiparameter flow cytometric detection and analysis of rare cells in in vivo models of cancer metastasis

Mallin,

Rolle,

Pienta

et al. 2024

Biology Methods and Protocols

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Rapid and reliable circulating tumor cell (CTC) and disseminated tumor cell (DTC) detection is critical for rigorous evaluation of in vivo metastasis models. Clinical data shows that each step of the metastatic cascade presents increasing barriers to success, limiting the number of successful metastatic cells to fewer than 1 in 1,500,000,000. As such, it is critical for scientists to employ approaches that allow for evaluation of metastatic competency at each step of the cascade. Here, we present a flow cytometry-based method that enables swift and simultaneous comparison of both CTCs and DTCs from single animals, enabling evaluation of multiple metastatic steps within a single model system. We present the necessary gating strategy and optimized sample preparation conditions necessary to capture CTCs and DTCs using this approach. We also provide proof-of-concept experiments emphasizing the appropriate limits of detection of these conditions. Most importantly, we successfully recover CTCs and DTCs from murine blood and bone marrow. In supplemental materials, we expand the applicability of our method to lung tissue and exemplify a potential multi-plexing strategy to further characterize recovered CTCs and DTCs. This approach to multiparameter flow cytometric detection and analysis of rare cells in in vivo models of metastasis is reproducible, high-throughput, broadly applicable and highly adaptable to a wide range of scientific inquiries. Most notably, it simplifies the recovery and analysis of CTCs and DTCs from the same animal, allowing for a rapid first look at the comparative metastatic competency of various model systems throughout multiple steps of the metastatic cascade.

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Section: Discussionmentioning

confidence: 99%

Multiparameter flow cytometric detection and analysis of rare cells in in vivo models of cancer metastasis

Mallin,

Rolle,

Pienta

et al. 2024

Biology Methods and Protocols

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“…Alu115 and Alu247 did not show a significant difference (p=0.977 and p=0.722, respectively), but DII was the only one that was significantly greater in the late stages compared to the early stages (p=<0.001). Table (4) and diagram (3). Additionally, we examined the parameters in patients who were positive for LN vs negative for LN.…”

Section: Assessment Of Alu115 247 and DII As Markers For Prognosismentioning

confidence: 99%

“…In Egypt, BC accounts for 35.1% of cases among females and reports stated that it carries bad prognosis with 29% mortality rate (2) . Many studies have found increased concentrations of cfDNA and its integrity in various types of malignancy including BC (3,4) . Because the advantage of cfDNA as a non-invasive biomarker, numerous samplings can be obtained to follow up dynamic changes in tumor burden (5) .…”

Section: Introductionmentioning

confidence: 99%

“…Hence, fragmentomic analysis and obtaining idea of DNA length could predict cfDNA source. Accordingly, higher concentrations of longer necrotic circulating DNA fragments have been proposed to be a convenient parameter of malignancy (4) . Various studies used Aluquantitative PCR that is based on using Alu115 primer to amplify short apoptotic DNA fragments and ALU247 primer to amplify long necrotic DNA fragments.…”

Section: Introductionmentioning

confidence: 99%

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DNA Integrity Index as a Molecular Marker for Prediction of Tumor Burden in Breast Cancer

Ghorab,

Abd-Elmotalib Mansy,

Saleh

et al. 2024

Ain Shams Medical Journal

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Background: Globally, the incidence and death rate from of breast cancer (BC) are rising quickly; by 2040, there may be one million deaths and over 3 million new cases of BC. Various studies assessed the usefulness of DNA integrity index (DII) as marker for diagnosis and prognosis in variety of solid tumors. Aim of the work:We aimed to evaluate DII's clinical usefulness as a molecular marker for BC detection, prognosis prediction and assessment of tumor burden in Egyptian BC female patients. Patients and methods:This study included 150 female patients with BC, and 75 healthy controls. Measurement of cfDNA ALU 115 and 247 fragments was by real-time polymerase chain reaction and DII was calculated. Results:In comparison to controls, BC patients had a highly statistically significant rise in DII (p=<0.001). A highly significant increase in DII was observed in cases with early stages compared to controls (p=<0.001). Also, it was showed that patients with metastasis had greater levels of DII than patients without metastasis (p=0.002). DII was positively correlated with tumor size (r=0.64, p= <0.001) and with stage (r=0.73, p=<0.001). ROC curve was constructed using DII to discriminate between BC cases and controls. The optimal cut off was greater than 0.51 with sensitivity 88%, specificity 92%, PPV 96%, NPV 79% and the AUC was 0.95 with 95% CI (0.90-0.99). Conclusions:This study suggests the possible use of DII as promising adjuvant marker in early BC detection, and it may be used as a prognostic biomarker for detection of BC tumor progression and tumor burden.

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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.…”

Section: Introductionmentioning

confidence: 99%

Estimation of ALU Repetitive Element in Plasma as a Cost-Effective Liquid Biopsy Tool for Disease Prognosis in Breast Cancer

Nair¹,

Ramesh²,

Chandrakala³

et al. 2022

Preprint

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

Cited by 6 publications

References 59 publications

Multiparameter flow cytometric detection and analysis of rare cells in in vivo models of cancer metastasis

Multiparameter flow cytometric detection and analysis of rare cells in in vivo models of cancer metastasis

DNA Integrity Index as a Molecular Marker for Prediction of Tumor Burden in Breast Cancer

Estimation of ALU Repetitive Element in Plasma as a Cost-Effective Liquid Biopsy Tool for Disease Prognosis in Breast Cancer

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