Biomarker: circulating tumor DNA (ctDNA)

Biomarker subtype: DNA

Clinical application: prognosis(tumor recurrence)

Histology type: endometrial carcinoma

Stage: high risk

Country: China

Region: Shanghai

Followed up time : >25 months

Sample type : plasma

Clinical method: droplet digital PCR (ddPCR)

Expression pattern : ctDNA detect

Expression elevation: Baseline ctDNA level (median cfDNA levels, mutant copies, mutant allele fraction and ctDNA detection rate)

Description: Personalized ctDNA detection was effective and stable for high-risk EC. CtDNA tracking in post-operative plasma is valuable for predicting tumor recurrence.

Survival figure legend: Correlation between tumor relapse and pre/post-operative ctDNA detection. $ CtDNA and CA125/HE4 detection in disease-free and relapsed patients.

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860194/figure/Fig4/$ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860194/figure/Fig5/

Detailed Description: Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the bloodstream that is not associated with cells. ctDNA should not be confused with cell-free DNA (cfDNA), a broader term which describes DNA that is freely circulating in the bloodstream, but is not necessarily of tumor origin. Because ctDNA may reflect the entire tumor genome, it has gained traction for its potential clinical utility; “liquid biopsies” in the form of blood draws may be taken at various time points to monitor tumor progression throughout the treatment regimen.[PMID 28233803] ctDNA originates directly from the tumor or from circulating tumor cells (CTCs),[PMID 23491080] which describes viable, intact tumor cells that shed from primary tumors and enter the bloodstream or lymphatic system. The precise mechanism of ctDNA release is unclear. The biological processes postulated to be involved in ctDNA release include apoptosis and necrosis from dying cells, or active release from viable tumor cells.[PMID 21562580][PMC 1173871][PMID 11694251][PMID 1149042][PMID 4505646] Studies in both human (healthy and cancer patients)[8] and xenografted mice[9] show that the size of fragmented cfDNA is predominantly 166bp long, which corresponds to the length of DNA wrapped around a nucleosome plus a linker. Fragmentation of this length might be indicative of apoptotic DNA fragmentation, suggesting that apoptosis may be the primary method of ctDNA release. The fragmentation of cfDNA is altered in the plasma of cancer patients.[PMID 21909401][PMID 30404863] In healthy tissue, infiltrating phagocytes are responsible for clearance of apoptotic or necrotic cellular debris, which includes cfDNA.[PMID 17516210] ctDNA in healthy patients is only present at low levels but higher levels of ctDNA in cancer patients can be detected with increasing tumor sizes.[PMID 33310847] This possibly occurs due to inefficient immune cell infiltration to tumor sites, which reduces effective clearance of ctDNA from the bloodstream.[PMID 17516210] Comparison of mutations in ctDNA and DNA extracted from primary tumors of the same patients revealed the presence of identical cancer-relevant genetic changes. [PMID 7918071][K-ras point mutations in the blood plasma DNA of patients with colorectal tumors in Challenges of Modern Medicine. Vol. 5. pp. 141–150.] This led to the possibility of using ctDNA for earlier cancer detection and treatment follow up. [PMID 25079538]