Clinical Relevance of Alterations in Quantity and Quality of Plasma DNA in Colorectal Cancer Patients: Based on the Mutation Spectra Detected in Primary Tumors

Lin, Jen Kou; Lin, Pei; Lin, Chun-Ming; Jiang, Jeng Kai; Yang, Shung Haur; Liang, Wen Yi; Chen, Wei Shone; Chang, Shih Ching

doi:10.1245/s10434-014-3804-5

Cited by 57 publications

(55 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The median copy number of cpDNA per mL of all the patients enrolled was 4280 copies/mL, which was ∼3 times of the best cut‐off value and was defined as the cut‐off value of high or low cpDNA expression. The definition of the cut‐off value of cpDNA expression as the median copy number of cpDNA per mL was the same as a previous report …”

Section: Methodsmentioning

confidence: 99%

Clinical significance of circulating plasma DNA in gastric cancer

Fang

Lan

Huang

et al. 2016

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p 5 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5-year overall survival rates (39.2% vs. 45.8%, p 5 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p 5 0.036) and exhibited a lower 5-year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p 5 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer.Although the worldwide incidence of gastric cancer has been declining, it remains the 5th most common cancer, accounting for 723,000 deaths worldwide in 2012.1 Surgical resection and lymphadenectomy are the standard of care for curing gastric cancer, and the tumor stage provides important prognostic insight. 2Peritoneal recurrence is the most common pattern of gastric cancer recurrence after curative surgery and is often

show abstract

Section: Methodsmentioning

confidence: 99%

Clinical significance of circulating plasma DNA in gastric cancer

Fang

Lan

Huang

et al. 2016

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…56 Regarding KRAS-mutated tumors, sensitivity to detect KRAS-mutated ctDNA ranges from 20% to 60% for non-metastatic disease (with higher sensitivity in stage III than in stages I-II) to 80%-100% for metastatic disease. 57,58 By comparison, the fecal immunochemical test (FIT) had a sensitivity of 79% (95% confidence interval (CI) = 69%-86%) and specificity of 94% (95% CI = 92%-95%) for CRC screening, based on data from 19 studies in asymptomatic, average-risk adults. 59 An alternative approach to identifying ctDNA is aberrant DNA methylation of specific promoter regions, which is more consistent between tumors than mutations.…”

Section: Cancer Diagnosis and Screeningmentioning

confidence: 99%

Future perspectives of circulating tumor DNA in colorectal cancer

et al. 2017

View full text Add to dashboard Cite

Tumor biopsy is currently the gold standard for diagnosis and in determining cell signaling pathways involved in the development of treatment resistance. However, there are major challenges with this technique, including the need for serial sampling to monitor treatment resistance, which is invasive and also has the potential for selection bias due to intra-tumoral and inter-tumoral heterogeneity. These challenges highlight the need for more effective methods for obtaining Tumor samples. Liquid biopsy analyzes genetic material or tumor cells shed into the blood from the primary tumor and metastatic sites and consequently provides a comprehensive, real-time picture of the tumor burden in an individual patient. Indeed, liquid biopsy has the potential to revolutionize cancer management. Here, we review recent studies on the potential clinical applications of liquid biopsy using circulating tumor DNA in colorectal cancer, including screening, diagnosis, detection of minimal residual disease after surgery, detection of recurrence, prognosis, predicting treatment response, monitoring tumor burden or response during treatment, and tracking resistance. We also discuss recent data demonstrating the utility of detecting KRAS-mutated circulating tumor DNA, both at diagnosis to determine an appropriate treatment strategy and during anti-epidermal growth factor receptor therapy to predict treatment resistance. The future integration of liquid biopsy into clinical practice is discussed, together with alternative approaches and key questions that need to be answered in future clinical studies before this technology can be implemented and used routinely.

show abstract

“…A few studies performed on CRC patients support the concept of serological staging by reporting a statistically significant association between CK20 levels or tumor-specific DNA mutations in the DNA from the peripheral blood and the tumor stage (12,25–27). Therefore, the aim of the present study was to assess whether the detection of the expression of CK20 and the presence of KRAS and BRAF tumor-specific mutations in the peripheral blood can be used to determine the stage of a CRC patient prior to surgery and the R status after surgery.…”

Section: Discussionmentioning

confidence: 97%

Role of specific DNA mutations in the peripheral blood of colorectal cancer patients for the assessment of tumor stage and residual disease following tumor resection

et al. 2016

View full text Add to dashboard Cite

In the present study, the detection of tumor-specific KRAS proto-oncogene, GTPase (KRAS) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations in the peripheral blood of colorectal cancer (CRC) patients at all stages and adenomas was used for the estimation of disease stage prior to surgery and for residual disease following surgery. A total of 65 CRC patients were enrolled. The primary tumor tested positive for the specific mutations (KRAS mutations in codons 12, 13, 61, 117 or 146 and BRAF mutations in codon 600) in 35 patients. In all these patients, the specimen of normal bowel resected with the tumor was also tested for the presence of the same mutations in order to exclude the germ-line mutations. Only patients who tested positive for the specific mutation in the primary tumor were included in further analysis for the presence of tumor-specific mutation in the peripheral blood. No statistically significant differences were found between the detection rates of tumor mutations in the blood and different tumor stages (P=0.491). However, statistically significant differences in the proportions of patients with detected tumor-specific DNA mutations in the peripheral blood were found when comparing the groups of patients with R0 and R2 resections (P=0.038). Tumor-specific DNA mutations in the peripheral blood were more frequently detected in the patients with an incomplete surgical clearance of the tumor due to macroscopic residual disease (R2 resections). Therefore, the study concludes that the follow-up of somatic KRAS- and BRAF-mutated DNA in the peripheral blood of CRC patients may be useful in assessing the surgical clearance of the disease.

show abstract

Clinical Relevance of Alterations in Quantity and Quality of Plasma DNA in Colorectal Cancer Patients: Based on the Mutation Spectra Detected in Primary Tumors

Abstract: Plasma DNA alteration is a useful tool for clinical surveillance of colorectal cancer patients and might be an independent prognosticator.

Cited by 57 publications

References 29 publications

Clinical significance of circulating plasma DNA in gastric cancer

Clinical significance of circulating plasma DNA in gastric cancer

Future perspectives of circulating tumor DNA in colorectal cancer

Role of specific DNA mutations in the peripheral blood of colorectal cancer patients for the assessment of tumor stage and residual disease following tumor resection

Contact Info

Product

Resources

About