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Increased Free Circulating DNA Integrity Index as a Serum Biomarker in Patients with Colorectal Carcinoma
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 Title & Authors
Increased Free Circulating DNA Integrity Index as a Serum Biomarker in Patients with Colorectal Carcinoma
El-Gayar, Dina; El-Abd, Nevine; Hassan, Noha; Ali, Reem;
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 Abstract
Background: Cell-free DNA circulating in blood is a candidate biomarker for malignant tumors. Unlike uniformly truncated DNA released from apoptotic non diseased cells, DNA released from necrotic cancer cells varies in size. Objectives: To measure the DNA integrity index in serum and the absolute DNA concentration to assess their clinical utility as potential serum biomarkers for colorectal carcinoma (CRC) compared to CEA and CA19-9. Materials and Methods: Fifty patients with CRC, 10 with benign colonic polyps and 20 healthy sex and age matched volunteers, were investigated by real time PCR of ALU repeats (ALU q-PCR) using two sets of primers (115 and 247 bp) amplifying different lengths of DNA fragments. The DNA integrity index was calculated as the ratio of q-PCR results of ALU 247/ALU 115bp. Results: Serum DNA integrity was statistically significantly higher in CRC patients compared to the benign and control groups (p<0.001). ROC curves for differentiating CRC patients from normal controls and benign groups had areas under curves of 0.90 and 0.85 respectively. Conclusions: The DNA integrity index is superior to the absolute DNA concentration as a potential serum biomarker for screening and diagnosis of CRC. It may also serve as an indicator for monitoring the progression of CRC patients. Combining CEA and CA19-9 with either of the genetic markers studied is better than either of them alone.
 Keywords
Colorectal carcinoma;DNA integrity index;ALU q-PCR;CEA/CA19-9;
 Language
English
 Cited by
1.
Circulating Cell-Free DNA in Dogs with Mammary Tumors: Short and Long Fragments and Integrity Index, PLOS ONE, 2017, 12, 1, e0169454  crossref(new windwow)
2.
Alteration of the exDNA profile in blood serum of LLC-bearing mice under the decrease of tumour invasion potential by bovine pancreatic DNase I treatment, PLOS ONE, 2017, 12, 2, e0171988  crossref(new windwow)
3.
Methodological, biological and clinical aspects of circulating free DNA in metastatic colorectal cancer, Acta Oncologica, 2017, 56, 1, 7  crossref(new windwow)
 References
1.
Agostini M, Pucciarelli M, Vittoria M (2011). Circulating cell-free DNA: a promising marker of pathologic tumor response in rectal cancer patients receiving preoperative chemoradiotherapy. Ann Surg Oncol, 18, 2461-8. crossref(new window)

2.
Casadio V, Foca F, Zingaretti C, et al (2013). Gene methylation in rectal cancer: predictive marker of response to chemoradiotherapy. J Cell Physiol, 228, 2343-9. crossref(new window)

3.
Chen H, Sun LY, Zheng HQ, et al (2012). Total serum DNA and DNA integrity: diagnostic value in patients with hepatitis B virus-related hepatocellular carcinoma. Pathol, 44, 318-24. crossref(new window)

4.
Cordaux R, Batzer MA (2009). The impact of retrotransposons on human genome evolution. Nature Reviews Genetics, 10, 691-703. crossref(new window)

5.
da Silva Filho BF, Gurgel AP, Neto MA, et al (2013). Circulating cell-free DNA in serum as a biomarker of colorectal cancer. J Clin Pathol, 66, 775-8. crossref(new window)

6.
David A, Lieberman D, Douglas K, et al (2012). Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US multi-society task force on colorectal cancer. Gastroentrol, 143, 844-85. crossref(new window)

7.
Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al (2013). Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 49, 1374-403. crossref(new window)

8.
Fong SL, Zhang JT, Lim CK, et al (2009). Comparison of 7 methods for extracting cell-free DNA from serum samples of colorectal cancer patients. Clin Chem, 55, 587-9. crossref(new window)

9.
Gao YJ, He YJ, Yang ZL (2010). Increased integrity of circulating cell free DNA in plasma of patients with acute leukemia. Clin Chem Lab Med, 48, 1651-6.

10.
Hanley R, Christ KM, Canes D (2006). DNA integrity assay: a plasma-based screening tool for the detection of prostate cancer. Clin Cancer Res, 12, 4569-74. crossref(new window)

11.
Hao TB, Shi W, Shen XJ2, et al (2014). Circulating cell-free DNA in serum as a biomarker for diagnosis and prognostic prediction of colorectal cancer. Br J Cancer, 111, 1482-9 crossref(new window)

12.
Labianca R, Nordlinger B, Beretta.G, et al (2013). Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 24, 64-72

13.
Leszinski G, Lehner J, Gezer U, et al (2013). Increased DNA integrity in colorectal cancer. In Vivo, 3, 299-303.

14.
Luo L, Ting W, Qian H, et al (2014). Changes of TCR repertoire diversity in colorectal cancer after erbitux (cetuximab) in combination with chemotherapy. Am J Cancer Res. 4, 924-33.

15.
Maestranzi S, Przemioslo R, Mitchell H, et al (1998). The effect of benign and malignant liver disease on the tumor markers CA 19-9 and CEA. Ann Clin Biochem, 35, 99-103. crossref(new window)

16.
Maio G, Rengucci C, Zoli W, et al (2014). Circulating and stool nucleic acid analysis for colorectal cancer diagnosis. World J Gastroenterol, 20, 957-67. crossref(new window)

17.
Mead R, Duku M, Bhandari P, et al (2011). Circulating tumour markers can define patients with normal colons, benign polyps, and cancers. Br J Cancer, 105, 239-45. crossref(new window)

18.
Otero E, Chiara L, Rodriguez L, et al (2015). Serum sCD26 for colorectal cancer screening in family-risk individuals: comparison with fecal immunochemical test. British. J Cancer, 112, 375-81. crossref(new window)

19.
Pinzani P, Salvianti F, Zaccara S (2011). Circulating cell-free DNA in plasma of melanoma patients: qualitative and quantitative considerations. Clin Chim Acta, 412, 2141-5. crossref(new window)

20.
Umetani N, Kim J, Hiramatsu S, et al (2006). Increased integrity of free circulating DNA in sera of patients with colorectal or periampullary cancer: direct quantitative PCR for ALU repeats. Clinical Chemistry, 52, 61062-9.

21.
Wang H, Nekrutenko A, Li WH (2000). Densities, length proportions, and other distributional features of repetitive sequences in the human genome estimated from 430 megabases of genomic sequence. Gene, 259, 81-8. crossref(new window)

22.
Wang M, Li Y, Wang Z, et al (2015). The PKA $RI{\alpha}$/A-kinase anchoring proteins 10 signaling pathway and the prognosis of colorectal cancer. J Gastroenterol Hepatol, 30, 496-503. crossref(new window)

23.
Zaher MN, Mahpar E, Rafiq S, et al (2014). Clinical features and outcome of sporadic colorectal carcinoma in young patients: a cross-sectional analysis from a Developing Country. ISRN Oncol, 2014, 461570.