Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Tumor biomarkers have multiple characteristics, including noninvasive, repeatable analysis and real-time monitoring, and they have important application value in early diagnosis and prognosis monitoring of hepatocellular carcinoma (HCC). In recent years, the researches on tumor markers of HCC have developed rapidly. There are not only traditional serological tumor markers, such as alpha fetoprotein, des-gamma carboxy prothrombin, Golgi protein 73, glypican-3, etc., but also new emerging "liquid biopsy" tumor markers, such as circulating tumor cells, circulating tumor DNA etc. Further study on the correlation between tumor biomarkers and HCC can provide reference for the treatment and prognosis evaluation of HCC.

The incidence of colorectal cancer (CRC) is increasing year by year, and early diagnosis is of great significance to improve the prognosis of patients. Circulating cell-free nucleic acid (cfNA) has the advantages of non-invasive, real-time monitoring, and overcoming tumor heterogeneity. The characteristics of cfNA content, mutation, methylation and fragmentation patterns provid important reference value for early diagnosis, curative effect monitoring, prognosis judgment and medication guidance of CRC. However, the practical application of cfNA in the clinical diagnosis and treatment of CRC still needs to solve the problems of unstandardized detection technology, high detection cost, screening of markers with high diagnostic efficacy, and construction of multi-combination models. These challenges will provide new directions for future cfNA research.

Objective To investigate the relationship between the polymorphism of cytochrome P450 19 (CYP19) gene rs10046 and the risk of colon and rectal cancer.Methods Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze gene polymorphism in CYP 19 gene rs10046 in 198 cases of colon and rectal cancer patients (case group) and 309 cases of healthy controls (control group).The genotype frequency and relative risk of CYP19 gene rs10046 between the two groups were compared and the relationship with the clinicopathological features of colorectal cancer was analyzed.Results In case group,the prevalence rates of CYP19 rs10046 genotypes C/C,C/T and T/T were 28.3％,44.4％ and 27.3％,respectively,and 17.2％,51.8％ and 31.1％ in the control group,respectively,with statistical significant difference (P ＜ 0.05).Compared with wild-type C/C,the susceptibility of colorectal cancer with the genotypes of C/T and T/T was decreased by 0.521 (95％ CI:0.330-0.822)and 0.532 (95 ％ CI:0.322-0.880) respectively.Moveover,in the non-smoking group,the risk of colorectal cancer with genotype T/T or C/T was decreased by 0.409 (95％ CI:0.210-0.798) compared with genotype C/C.The interaction was not exist in smoking group.Conclusions The polymorphism of CYP19 gene rs10046 is related to the susceptibility of colon and rectal cancer.The T/T,C/T genotype of CYP19 rs10046 decrease the risk of colon and rectal cancer,and which might be the protective factor of colon and rectal cancer.

Liver cancer is a malignant tumor with the characteristics of high morbidity and mortality.However,the routine detection methods for the liver cancer such as imaging tests and pathological detection are with low specificity and sensitivity.And it's also hard to detect the condition of patients dynamically.Cell-free DNA (cfDNA) is the DNA fragment that is away from the extracellular and exists in the blood,which contains genetic information from the organism.The related disease information could be reflected on the cfDNA in patients with liver cancer,indicating that cfDNA has great potential in the screening,diagnosis,treatment and prognosis of liver cancer.The clinical applications of cfDNA can make up for the deficiency of existing detection methods and achieve noninvasive and dynamic monitoring of liver cancer.This article will present a review on the progress of clinical applications of cfDNA in liver cancer.