scholarly journals Patients with polyclonal hepatocellular carcinoma are at a high risk of early recurrence and have a poor recurrence-free survival period

2022 ◽  
Author(s):  
Masaki Kaibori ◽  
Kazuko Sakai ◽  
Hideyuki Matsushima ◽  
Hisashi Kosaka ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Deep Sequencing ◽  
Copy Number ◽  
Snp Array ◽  
Early Recurrence ◽  
Copy Number Variations ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Targeted Deep Sequencing

Abstract Background/purpose of the study Tumor heterogeneity based on copy number variations is associated with the evolution of cancer and its clinical grade. Clonal composition (CC) represents the number of clones based on the distribution of B-allele frequency (BAF) obtained from a genome-wide single nucleotide polymorphism (SNP) array. A higher CC number represents a high degree of heterogeneity. We hypothesized and evaluated that the CC number in hepatocellular carcinoma (HCC) tissues might be associated with the clinical outcomes of patients. Methods Somatic mutation, whole transcriptome, and CC number based on copy number variations of 36 frozen tissue samples of operably resected HCC tissues were analyzed by targeted deep sequencing, transcriptome analysis, and SNP array. Results The samples were classified into the heterogeneous tumors as poly-CC (n = 26) and the homogeneous tumors as mono-CC (n = 8). The patients with poly-CC had a higher rate of early recurrence and a significantly shorter recurrence-free survival period than the mono-CC patients (7.0 months vs. not reached, p = 0.0084). No differences in pathogenic non-synonymous mutations, such as TP53, were observed between the two groups when targeted deep sequencing was applied. A transcriptome analysis showed that cell cycle-related pathways were enriched in the poly-CC tumors, compared to the mono-CC tumors. Poly-CC HCC is highly proliferative and has a high risk of early recurrence. Conclusion CC is a possible candidate biomarker for predicting the risk of early postoperative recurrence and warrants further investigation.

scholarly journals Patients with polyclonal hepatocellular carcinoma are at a high risk of early recurrence and have a poor recurrence-free survival period

2021 ◽  
Author(s):  
Masaki Kaibori ◽  
Kazuko Sakai ◽  
Hideyuki Matsushima ◽  
Hisashi Kosaka ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Copy Number ◽  
Snp Array ◽  
Early Recurrence ◽  
Copy Number Variations ◽  
Survival Period ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
A Genome

Abstract Background/purpose of the study Tumor heterogeneity based on copy number variations is associated with the evolution of cancer and its clinical grade. Clonal composition (CC) represents the number of clones based on the distribution of B-allele frequency (BAF) obtained from a genome-wide single nucleotide polymorphism (SNP) array. A higher CC number represents a high degree of heterogeneity. We hypothesized and evaluated that the CC number in hepatocellular carcinoma (HCC) tissues might be associated with the clinical outcomes of patients. Methods Somatic mutation, whole transcriptome, and copy number variations of 36 frozen tissue samples of operably resected HCC tissues by targeted deepsequencing, RNAseq and SNP array. Results The samples were classified the heterogeneous tumors as poly-CC (n = 26) and the homogeneous tumors as mono-CC (n = 8). The patients with poly-CC had a higher rate of early recurrence and a significantly shorter recurrence-free survival period than the mono-CC patients (7.0 vs. not reached, p = 0.0084). No differences in pathogenic non-synonymous mutations, such as TP53, were observed between the two groups when targeted deep sequencing was applied. A transcriptome analysis showed that cell cycle-related pathways were enriched in the poly-CC tumors, compared with the mono-CC tumors. poly-CC HCC is highly proliferative and has a high risk of early recurrence. Conclusion CC is a candidate biomarker for predicting the risk of early postoperative recurrence and warrants further investigation.

scholarly journals Inflammatory indexes in preoperative blood routine to predict early recurrence of hepatocellular carcinoma after curative hepatectomy

BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
YiFeng Wu ◽  
ChaoYong Tu ◽  
ChuXiao Shao
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Tumour Size ◽  
Area Under The Curve ◽  
Early Recurrence ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Lymphocyte Ratio ◽  
Inflammatory Index ◽  
Curative Hepatectomy

Abstract Background The inflammation indexes in blood routine play an essential role in evaluating the prognosis of patients with hepatocellular carcinoma, but the effect on early recurrence has not been clarified. The study aimed to investigate the risk factors of early recurrence (within 2 years) and recurrence-free survival after curative hepatectomy and explore the role of inflammatory indexes in predicting early recurrence. Methods The baseline data of 161 patients with hepatocellular carcinoma were analyzed retrospectively. The optimal cut-off value of the inflammatory index was determined according to the Youden index. Its predictive performance was compared by the area under the receiver operating characteristic curve. Logistic and Cox regression analyses were used to determine the risk factors of early recurrence and recurrence-free survival. Results The area under the curve of monocyte to lymphocyte ratio (MLR) for predicting early recurrence was 0.700, which was better than systemic inflammatory response index (SIRI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic immune-inflammatory index (SII). MLR, tumour size, tumour differentiation and BCLC stage are all risk factors for early recurrence and recurrence-free survival of HCC. Combining the above four risk factors to construct a joint index, the area under the curve for predicting early recurrence was 0.829, which was better than single MLR, tumour size, tumour differentiation and BCLC stage. Furthermore, with the increase of risk factors, the recurrence-free survival of patients is worse. Conclusion The combination of MLR and clinical risk factors is helpful for clinicians to identify high-risk patients with early recurrence and carry out active postoperative adjuvant therapy to improve the prognosis of patients.

scholarly journals A prenatal diagnosis and genetics study of five pedigrees in the Chinese population with Xp22.31 microduplication

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianlong Zhuang ◽  
Yuanbai Wang ◽  
Shuhong Zeng ◽  
Chunling Lv ◽  
Yiming Lin ◽  
...  
Keyword(s):  
High Risk ◽  
Copy Number ◽  
Chinese Population ◽  
Phenotypic Diversity ◽  
Copy Number Variants ◽  
Snp Array ◽  
Copy Number Variations ◽  
Serological Screening ◽  
X Chromosomes ◽  
Human Phenotype

Abstract Background Copy number variations (CNVs) can contribute to human phenotype, phenotypic diversity and disease susceptibility, while others may benign. In the current study, an attempt to investigate the pathogenicity of CNVs in chromosome Xp22.31 was explored. Methods G-banding and SNP-array techniques were used to analyze chromosome karyotypes and CNVs in fetuses. Parents associate with five different pedigrees possessing high risk factors in pregnancy were considered with such parameters as advanced age, high risk of serological screening and ultrasound abnormalities. Results The fetuses’ amniotic fluid karyotypes were 46, XX and those of their parents with the five pedigrees revealed no abnormalities. Here, we noticed a series of individuals with Xp22.31 duplications ranging from 534.6 kb to 1.6 Mb. It was detected through SNP array that the fetuses in Pedigree 1 and 2 had ~ 600 kb duplications in the Xp22.31 region of their X chromosomes which contained two OMIM genes, HDHD1 (OMIM: 306480) and part of STS (OMIM: 300747). The fetuses of Pedigrees 3, 4 and 5 had 1.6 Mb duplication in the same chromosome which contained four OMIM genes: HDHD1 (OMIM: 306480), STS (OMIM: 300747), PNPLA4 (OMIM: 300102) and VCX (OMIM: 300229). The duplications in the fetuses of Pedigrees 1 and 5 were inherited from the non-phenotypic parents. Pedigrees 3 and 4 refused to perform parental verification. Finally, four of the five pedigrees continue towards pregnancy with no abnormalities being observed during followed-ups. Conclusion Our study first showed duplications of Xp22.31 in Chinese population. Clinical and genetic investigation on five different pedigrees, we consider the duplication of these fragments as likely benign copy number variants (CNVs). We suggest that the duplications of Xp22.31 with recurrent duplication as a benign CNVs .

Phase I trial of sorafenib following liver transplantation in patients with high-risk hepatocellular carcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 401-401
Author(s):  
Abby B. Siegel ◽  
Anthony B. El-Khoueiry ◽  
Richard S. Finn ◽  
Katherine Guthrie ◽  
Alan P. Venook ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
High Risk ◽  
Phase I ◽  
Phase I Trial ◽  
Recurrence Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Risk Of Recurrence ◽  
Post Transplant

401 Background: Liver transplantation (LT) offers excellent long-term survival for hepatocellular carcinoma (HCC) patients who are within established criteria. For those outside such criteria, or with high risk pathologic features in the explant, HCC recurrence rates after LT are high. No treatment has been shown to decrease risk of recurrence post-LT. We conducted a multicenter phase I trial of sorafenib in LT patients with high-risk HCC. Methods: Subjects had pathologically proven high-risk HCC defined as outside Milan (pre- or post-transplant), poorly differentiated tumors, or tumors with vascular invasion. We used a standard 3+3 phase I design, beginning drug between 4 and 16 weeks after LT, with planned duration of treatment of 24 weeks. Cohort dosages were: 1) 200 mg per day, 2) 200 mg twice a day, 3) 200 mg/400 mg per day 4) 400 mg BID. Correlative studies included circulating endothelial cells (CECs) and plasma biomarkers collected prior to treatment, at 1 month, and at recurrence in a subset of subjects, and tumor expression of p-Erk, p-Akt, and c-Met in tissue microarrays. Results: We enrolled 14 patients. Median age was 63 years, and 93% were men. 71% had underlying HCV and 21% had HBV. Maximum tolerated dose (MTD) was 200 mg BID; only 43% of patients received >80% of planned dose. Grade 3-4 toxicities seen in >10% of subjects included: leukopenia (29%), LFT abnormalities (21%), hypertension (14%), hand-foot syndrome (14%) and diarrhea (14%). Over a median follow-up of 953 days, 1 patient died and 4 recurred, with a median recurrence-free survival of 716 days for the 4 patients who recurred. Mean CEC number at baseline was 21 cells/4 ml for those who recurred, and 80 cells/4 ml for those who did not (p=0.10). Mean sVEGFR2 levels decreased after 1 month on sorafenib (p=0.09), but did not correlate with recurrence. There was a trend for tumor c-Met expression with increased risk of recurrence. Conclusions: Post-transplant sorafenib is feasible and tolerable at 200 mg PO BID. Recurrence-free survival appears longer than expected but needs further validation in a larger study. Clinical trial information: NCT00997022.

scholarly journals A Novel Epigenetic Machine Learning Model to Define Risk of Progression for Hepatocellular Carcinoma Patients

2021 ◽  
Vol 22 (3) ◽  
pp. 1075
Author(s):  
Luca Bedon ◽  
Michele Dal Bo ◽  
Monica Mossenta ◽  
Davide Busato ◽  
Giuseppe Toffoli ◽  
...  
Keyword(s):  
Machine Learning ◽  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Progression Free Survival ◽  
Low Risk ◽  
Functional Enrichment ◽  
Free Survival ◽  
High Risk Patients ◽  
Risk Of Progression ◽  
Risk Patients

Although extensive advancements have been made in treatment against hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfied. It is now clearly established that extensive epigenetic changes act as a driver in human tumors. This study exploits HCC epigenetic deregulation to define a novel prognostic model for monitoring the progression of HCC. We analyzed the genome-wide DNA methylation profile of 374 primary tumor specimens using the Illumina 450 K array data from The Cancer Genome Atlas. We initially used a novel combination of Machine Learning algorithms (Recursive Features Selection, Boruta) to capture early tumor progression features. The subsets of probes obtained were used to train and validate Random Forest models to predict a Progression Free Survival greater or less than 6 months. The model based on 34 epigenetic probes showed the best performance, scoring 0.80 accuracy and 0.51 Matthews Correlation Coefficient on testset. Then, we generated and validated a progression signature based on 4 methylation probes capable of stratifying HCC patients at high and low risk of progression. Survival analysis showed that high risk patients are characterized by a poorer progression free survival compared to low risk patients. Moreover, decision curve analysis confirmed the strength of this predictive tool over conventional clinical parameters. Functional enrichment analysis highlighted that high risk patients differentiated themselves by the upregulation of proliferative pathways. Ultimately, we propose the oncogenic MCM2 gene as a methylation-driven gene of which the representative epigenetic markers could serve both as predictive and prognostic markers. Briefly, our work provides several potential HCC progression epigenetic biomarkers as well as a new signature that may enhance patients surveillance and advances in personalized treatment.

scholarly journals Expanded noninvasive prenatal testing for fetal aneuploidy and copy number variations and parental willingness for invasive diagnosis in a cohort of 18,516 cases

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yunsheng Ge ◽  
Jia Li ◽  
Jianlong Zhuang ◽  
Jian Zhang ◽  
Yanru Huang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
High Risk ◽  
Pregnant Women ◽  
Copy Number ◽  
Prenatal Testing ◽  
Copy Number Variations ◽  
Trisomy 13 ◽  
Noninvasive Prenatal Testing ◽  
Predictive Values ◽  
Parental Willingness

Abstract Background Noninvasive prenatal testing (NIPT) has been wildly used to screen for common aneuplodies. In recent years, the test has been expanded to detect rare autosomal aneuploidies (RATs) and copy number variations (CNVs). This study was performed to investigate the performance of expanded noninvasive prenatal testing (expanded NIPT) in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RATs), and copy number variations (CNVs) and parental willingness for invasive prenatal diagnosis in a Chinese prenatal diagnosis center. Methods A total of 24,702 pregnant women were retrospectively analyzed at the Women and Children’s Hospital from January 2013 to April 2019, among which expanded NIPT had been successfully conducted in 24,702 pregnant women. The high-risk expanded NIPT results were validated by karyotype analysis and chromosomal microarray analysis. All the tested pregnant women were followed up for pregnancy outcomes. Results Of the 24,702 cases, successful follow-up was conducted in 98.77% (401/446) of cases with common trisomies and SCAs, 91.95% (80/87) of RAT and CNV cases, and 76.25% (18,429/24,169) of cases with low-risk screening results. The sensitivity of expanded NIPT was 100% (95% confidence interval[CI], 97.38–100%), 96.67%(95%CI, 82.78–99.92%), and 100%(95%CI, 66.37–100.00%), and the specificity was 99.92%(95%CI, 99.87–99.96%), 99.96%(95%CI, 99.91–99.98%), and 99.88% (95%CI, 99.82–99.93%) for the detection of trisomies 21, 18, and 13, respectively. Expanded NIPT detected 45,X, 47,XXX, 47,XXY, XYY syndrome, RATs, and CNVs with positive predictive values of 25.49%, 75%, 94.12%, 76.19%, 6.45%, and 50%, respectively. The women carrying fetuses with Trisomy 21/Trisomy 18/Trisomy 13 underwent invasive prenatal diagnosis and terminated their pregnancies at higher rates than those at high risk for SCAs, RATs, and CNVs. Conclusions Our study demonstrates that the expanded NIPT detects fetal trisomies 21, 18, and 13 with high sensitivity and specificity. The accuracy of detecting SCAs, RATs, and CNVs is still relatively poor and needs to be improved. With a high-risk expanded NIPT result, the women at high risk for common trisomies are more likely to undergo invasive prenatal diagnosis procedures and terminate their pregnancies than those with unusual chromosome abnormalities.

Contrast-enhanced ultrasound–based ultrasomics score: a potential biomarker for predicting early recurrence of hepatocellular carcinoma after resection or ablation

2021 ◽  
Author(s):  
Hui Huang ◽  
Si-min Ruan ◽  
Meng-fei Xian ◽  
Ming-de Li ◽  
Mei-qing Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Risk Group ◽  
Early Recurrence ◽  
High Risk Group ◽  
Low Risk ◽  
Primary Hepatocellular Carcinoma ◽  
Contrast Enhanced Ultrasound ◽  
Combined Model ◽  
Contrast Enhanced

Objectives: This study aimed to construct a prediction model based on contrast-enhanced ultrasound (CEUS) ultrasomics features and investigate its efficacy in predicting early recurrence (ER) of primary hepatocellular carcinoma (HCC) after resection or ablation. Methods: This study retrospectively included 215 patients with primary HCC, who were divided into a developmental cohort (n = 139) and a test cohort (n = 76). Four representative images—grayscale ultrasound, arterial phase, portal venous phase and delayed phase —were extracted from each CEUS video. Ultrasomics features were extracted from tumoral and peritumoral area inside the region of interest. Logistic-regression was used to establish models, including a tumoral model, a peritumoral model and a combined model with additional clinical risk factors. The performance of the three models in predicting recurrence within 2 years was verified. Results: The combined model performed best in predicting recurrence within 2 years, with an area under the curve (AUC) of 0.845, while the tumoral model had an AUC of 0.810 and the peritumoral model one of 0.808. For prediction of recurrence-free survival, the 2 year cumulative recurrence rate was significant higher in the high-risk group (76.5%) than in the low-risk group (9.5%; p < 0.0001). Conclusion: These CEUS ultrasomics models, especially the combined model, had good efficacy in predicting early recurrence of HCC. The combined model has potential for individual survival assessment for HCC patients undergoing resection or ablation. Advances in knowledge: CEUS ultrasomics had high sensitivity, specificity and PPV in diagnosing early recurrence of HCC, and high efficacy in predicting early recurrence of HCC (AUC > 0.8). The combined model performed better than the tumoral ultrasomics model and peritumoral ultrasomics model in predicting recurrence within 2 years. Recurrence was more likely to occur in the high-risk group than in the low-risk group, with 2-year cumulative recurrence rates respectively 76.5% and 9.5% (p < 0.0001).

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