scholarly journals Plasma DNA Integrity as a Prognostic Biomarker for Colorectal Cancer Chemotherapy

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Feng Zhu ◽  
Jing Ma ◽  
Dongdong Ru ◽  
Ningning Wu ◽  
Yunhua Zhang ◽  
...  

Objectives. To verify whether the concentrations and integrity index of circulating cell-free DNA (cfDNA) in serum may be clinically useful for the progression monitoring of colorectal cancer (CRC) patients. Methods. Serum samples were collected from 76 primary CRC patients who underwent surgery, including 60 with chemotherapy and 43 with follow-up. Long (247 bp) and short (115 bp) DNA fragments in serum were detected by real-time quantitative PCR by amplifying the ALU repeats. Ten serum traditional biomarkers levels were detected by chemiluminescence immunoassay assay. Results. The median DNA integrity index (ALU247/ALU115) of serum DNA in the preoperative group was significantly higher than those in the postchemotherapy and the follow-up groups, while cfDNA concentration (ALU115) was significantly lower in the preoperative group compared with the postchemotherapy and the follow-up groups. CEA and CA242 were significantly lower in the postoperative group than in the preoperative group. Conclusions. Serum DNA integrity index (ALU247/115) may prove to be a promising candidate biomarker for prognostic prediction of CRC who underwent chemotherapy and during short-term follow-up.

Tumor Biology ◽  
2015 ◽  
Vol 37 (6) ◽  
pp. 7565-7572 ◽  
Author(s):  
Azza M. Kamel ◽  
Salwa Teama ◽  
Amal Fawzy ◽  
Mervat El Deftar

2019 ◽  
Vol 47 (5) ◽  
pp. 1829-1842 ◽  
Author(s):  
Weimin Xu ◽  
Yilian Zhu ◽  
Wei Shen ◽  
Wenjun Ding ◽  
Tingyu Wu ◽  
...  

Objective Prognostic prediction of colorectal cancer (CRC) remains challenging because of its heterogeneity. Aberrant expression of caudal-type homeobox transcription factor 2 (CDX2) is strongly correlated with the prognosis of CRC. Methods Tissue samples of patients with CRC who underwent surgery in Xinhua Hospital (Shanghai, China) from January 2010 to January 2013 were collected. CDX2 expression was semiquantitatively evaluated via immunohistochemistry. Results In total, 138 patients were enrolled in this study from a prospectively maintained institutional cancer database. The median follow-up duration was 57.5 months (interquartile range, 17.0–71.0 months). In the Cox proportional hazards model, low CDX2 expression combined with stage T4 CRC was significantly the worst prognostic factor for disease-free survival (hazard ratio = 7.020, 95% confidence interval = 3.922–12.564) and overall survival (hazard ratio = 5.176, 95% CI = 3.237–10.091). In the Kaplan–Meier survival analysis, patients with low CDX2 expression and stage T4 CRC showed significantly worse disease-free survival and overall survival than those with low CDX2 expression alone. Conclusion CDX2 expression combined with the T stage was more accurate for predicting the prognosis of CRC. Determining the prognosis of CRC using more than one variable is valuable in developing appropriate treatment and follow-up strategies.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10050-10050
Author(s):  
G. Nakayama

10050 Background: The incidence of colorectal cancer (CRC), one of the commonest malignancies worldwide, is still increasing. Despite advances in the diagnostic procedure, a large number of patients with CRC still presents with advanced disease. More sensitive and efficient diagnostic technique would make an impact on the prognosis of CRC patients through improving their compliance to the screening program, hence allowing earlier detection of the disease. To test the hypothesis that p16 methylation may serve as a marker for the diagnosis of CRC, we quantified the methylation levels of p16 in the serum DNA of CRC patients. Methods: Fresh specimens of 168 CRC and corresponding noncancerous tissues were obtained surgically at the Department of Surgery II, Nagoya University Graduate School of Medicine, together with the corresponding serum samples obtained 1 week prior to surgery. We defined the p16 methylation rate (p16 MR, in %) as follows: CM/(CM + CU) × 100%. CM is the concentration of methylated p16 sequences and CU is the concentration of unmethylated p16 sequences measured by quantitative methylation-specific PCR (Q-MSP) after bisulfite conversion. The relationship between the p16 MR and clinicopathologic findings were evaluated. Results: Aberrant p16 promoter methylation was found in 59% (99 of 168) of surgically resected CRC tissues. None of the corresponding normal tissues had methylated p16 sequences. 37% (37 of 99) serum samples of the CRC patients with tumoral p16 methylation had the same alterations. p16 MRs of 99 serum samples with tumoral p16 methylation were 0 to 68.9 (mean was 5.43±11.01). p16 MRs were significantly correlated with lymph node metastasis (P=0.001), lymphatic invasion (P=0.001) and venous invasion (P=0.020) of CRCs. p16 MRs increased significantly with tumor stage [stage I : 0.94 ± 1.68, stage II : 2.33 ± 5.19, stage III : 8.49 ± 14.22, stage IV : 10.03 ± 14.27 (P = 0.021)]. Moreover, the survival of patients with low p16 MR was significantly superior to those with high p16 MR (P=0.006). Conclusions: These results suggest that quantification of p16 methylation in the serum DNA might be a novel diagnostic tool and a prognostic factor for CRC. No significant financial relationships to disclose.


Author(s):  
Feryal Farouk Sherif ◽  
Mohamed Ali El Desouky ◽  
Mona Gebril ◽  
Osama Mahmoud Azmy

DNA Integrity index (DNA Int) and cell-free DNA (cf-DNA) represent promising biomarkers for epithelial ovarian cancer (EOC) detection. Tumor necrosis produces DNA fractions of different sizes, which contrasts apoptosis in normal tissue that releases smaller and more regular DNA fragments. Using ALU gene primers in quantitative PCR, the amplified cf-DNA is supposed to be either short fragments of 115 bp (ALU 115) or long fragments of 247 bp (ALU 247). ALU levels and DNA Int were determined in the plasma of 30 EOC patients, 30 benign cysts, and 15 healthy individuals. The mean values of DNA Int, ALU115, and ALU247 were elevated in malignant patients (0.51±0.09, 3.93 ng/ul ±1.93, 2.35 ng/ul ±1.1) respectively in comparison to healthy females (0.37±0.05; p < 0.001, 2.56 ng/ul ±0.9; p=0.027, 1.26±0.44; p< 0.01). A significant increase was shown in the mean values of DNA Int and ALU247 of EOC patients compared to those with benign cysts (0.4±0.06, p <0.001; 1.69±0.66, p =0.008) respectively. The area under the curve (AUC) for EOC versus healthy females achieved 0.913 (DNA Int), 0.696 (ALU115), and 0.809 (ALU247) with sensitivities and specificities were (86.7% and 93.3%) for DNA Int, (63.3% and 86.7%) for ALU115 and (76.7% and 86.7%) for ALU247 respectively. Furthermore, comparing patients with EOC versus those with benign cysts gave AUC of 0.834 (DNA Int), 0.564 (ALU115), and 0.681 (ALU247) with sensitivities and specificities were (80% and 80%) for DNA Int, (63.3% and 60%) for ALU115 and (60% and 80%) for ALU247 respectively. Higher DNA Int and plasma ALU247 could help in the assessment of EOC, and their measurements seem to have clinical value in diagnosis.


Author(s):  
Enrico Vizza ◽  
Giacomo Corrado ◽  
Martina De Angeli ◽  
Mariantonia Carosi ◽  
Emanuela Mancini ◽  
...  

Author(s):  
Enrico Vizza ◽  
Giacomo Corrado ◽  
Martina De Angeli ◽  
Mariantonia Carosi ◽  
Emanuela Mancini ◽  
...  

2006 ◽  
Vol 119 (11) ◽  
pp. 2673-2676 ◽  
Author(s):  
Wei-Wen Jiang ◽  
Marianna Zahurak ◽  
David Goldenberg ◽  
Yelena Milman ◽  
Hannah Lui Park ◽  
...  

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ramy Salem ◽  
Rasha Ahmed ◽  
Karim Shaheen ◽  
Mohammed Abdalmegeed ◽  
Heba Hassan

Abstract Background Efficient approaches for early detection of colorectal cancer offer opportunities to gain better treatment outcomes. Blood-based molecular biomarkers as DNA integrity index (DII) might represent a promising tumor marker in the future. The purpose of this study was to assess the clinical utility of the DII as a potential biomarker for colorectal cancer in 90 colorectal cancer patients, 30 patients with benign colorectal mass, and 30 age- and sex-matched healthy control subjects. PCR was used to assess the concentration of both ALU115 and ALU247. DII was calculated as the ratio of Q247/Q115. Results DII was significantly higher in colorectal cancer patients than both patients with benign colorectal mass and healthy controls. ROC curve was plotted using DII and the best cut-off was ≥ 0.60 with diagnostic sensitivity 93.0%, specificity 65.0%, PPV 80.0%, NPV 86.0%, and efficiency 82% with AUC (0.872) while the best cut-off for CEA was ≥ 1.4 ng/mL with diagnostic sensitivity 87.0%, specificity 60.0%, PPV 76%, NPV 75%, and efficiency 76% with AUC (0.79). Conclusions Our results suggest that DII is better than CEA as an early marker for colorectal cancer detection and may be used as a candidate biomarker for malignancy.


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