scholarly journals Alu-based cell-free DNA: a novel biomarker for screening of gastric cancer

Oncotarget ◽  
2016 ◽  
Vol 8 (33) ◽  
pp. 54037-54045 ◽  
Author(s):  
Chen Qian ◽  
Shaoqing Ju ◽  
Jing Qi ◽  
Jianmei Zhao ◽  
Xianjuan Shen ◽  
...  
BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Wang-Yang Pu ◽  
Rong Zhang ◽  
Li Xiao ◽  
Yong-You Wu ◽  
Wei Gong ◽  
...  

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 27-27
Author(s):  
Alejandra Alarcon ◽  
Wilda Olivares ◽  
Maria Jose Maturana ◽  
Andres Rodriguez ◽  
Oslando Padilla ◽  
...  

27 Background: Gastric cancer (GC) has been described as a multistep cascade of precursor lesions such as non-atrophic chronic gastritis (NACG), multiphocal atrophic gastritis (MAG), intestinal metaplasia (IM), low grade dysplasia (LGD) and high grade dysplasia (HGD) leading to early stages of GC (EGC). Currently, no non-invasive biomarkers for this progression are clinically available. We have previously identified a potential biomarker based on methylated Reprimo (RPRM) cell-free DNA (cfDNA) (Clin Cancer Res 2008;14:6264-9). In a cross-sectional study of 1,076 patients, we showed a sensitivity of 70.8% (95% CI: 60.3 to 81.3) and specificity of 74.3% (95% CI: 71.5 to 77) for methylated RPRM cfDNA, to distinguish NACG+MAG+IM+LGD vs HGD+EGC+AGC (Digestive Disease Week 2014 #108). However, the crude detection rate of EGC was only 46.6%. Here, we aim to explore the role of the combined use of methylated RPRM cfDNA and well stablished atrophy biomarkers such as pepsinogens, for non-invasive detection of EGC. Methods: A case-control study was performed including 237 patients (NACG:40; MAG:94; IM:55; LGD:11; HGD:5: EGC:15; AGC:17) scheduled for upper gastrointestinal endoscopy (UGIE). A heparinized venous blood sample was collected and methylated RPRM cfDNA and Immunoassays for Pepsinogen I and II were performed. Positive value was considered if methylated RPRM cfDNA > 0 copies/mL and PG I/II ratio <3.0 were found. Results: Overall sensitivity and specificity for the combined use of methylated RPRM cfDNA and PGI/II to distinguish NACG+MAG+IM+LGD vs HGD+EGC+AGC was 67.5% (95% CI: 50.2% to 81.9%) and 63% (95% CI: 55.9% to 69.7%), respectively. Positive and negative predictive values were 25.2% (95% CI: 17% to 34.9%) and 91.3% (95% CI: 85.3% to 95.4%), respectively. Importantly, crude detection rate for EGC increased from 46.6% to 86.7%. Conclusions: The combined use of methylated RPRM cfDNA and PGI/II reached similar sensitivity and specificity compared to methylated RPRM cfDNA alone to distinguish NACG+MAG+IM+LGD vs HGD+EGC+AGC. However, combined use of methylated RPRM cfDNA and PGI/II significantly improved the detection rate of EGC, a lesion with a curability rate over 95%.


2021 ◽  
Author(s):  
Kazuhide Ko ◽  
Yoshikazu Kananazawa ◽  
Takeshi Yamada ◽  
Daisuke Kakinuma ◽  
Kunihiko Matsuno ◽  
...  

2015 ◽  
Vol 148 (4) ◽  
pp. S-568
Author(s):  
Alejandro H. Corvalan ◽  
Marcelo Garrido ◽  
María J. Maturana ◽  
Oscar Corsi ◽  
Gerardo Ledermann

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 101-101
Author(s):  
Bettina Gabriele Muller ◽  
Alejandra Alarcon ◽  
Jorge M Arancibia ◽  
Francisca Alfaro ◽  
Jose Antonio Sola ◽  
...  

101 Background: Gastric cancer (GC) is one of the leading causes of cancer death. Perioperative chemotherapy (CT) for locally advanced GC improves curative resection rates and survival compared to surgery alone. Response assessment is challenging and no tumor markers have been validated for this purpose. We conducted a pilot study to investigate the role of methylated Reprimo (RPRM) cell-free DNA (cfDNA) as tumor marker for assessment of response to preoperative CT in patients enrolled in the study GOCCHI 2009-01 (NCT01633203). Methods: Patients with locally advanced GC referred to receive preoperative CT with Epirubicin + Cisplatin + Capecitabine for 3 cycles were offered to enter the study. Patients had to have operable GC, with baseline CT showing a transmural tumor and/or regional lymphnode metastasis with no distant spread assessed by a multidisciplinary tumor board. After the approval of the amendment of the protocol to allow blood sampling for tumor marker measurement and only if informed consent had been given, blood samples were taken at day one of each cycle of preoperative CT. The status of methylated RPRM cfDNA was assessed by Methylight and the number of copies per mL was determined. Patients with at least 2 samples were analyzed. Results: Thirteen patients signed the informed consent form for this substudy, and 11 patients had blood samples available for analysis. Of these, 8 patients had detectable methylated RPRM cfDNA on Day 1 of the first cycle (i.e. baseline). Five patients showed decrease in methylated RPRM cfDNA, while 5 patients had increased levels of the tumor marker in subsequent measurements. In one patient, methylated RPRM cfDNA was not detected in either of two assessments. One patient with a marked increase in methylated RPRM cfDNA after two cycles of CT had metastatic disease at laparotomy. Correlation between pathological findings and changes in methylated RPRM cfDNA will be presented. Conclusions: Our findings suggest that methylated RPRM cfDNA could serve as a novel tumor marker to assess response in locally advanced GC treated with preoperative chemotherapy. Further validation of these preliminary results is warranted.


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