Single-cell RNA sequencing of circulating tumor cells in hepatocellular carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE107747 | GEO | 2018/08/06
REPOSITORIES: GEO
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2018-04-29 | E-MTAB-5123 | biostudies-arrayexpress
Project description:Biomarker studies for early stage or preclinical hepatocellular carcinomas (HCC) are hindered by the difficulties of obtaining samples from asymptomatic individuals. We established animal models using irradiated mice to investigate circulating miRNA as non-invasive markers for detection of early stage HCC. We hypothesized that certain miRNAs that play pivotal roles in molecular pathways are conserved across species and identification of these miRNAs will facilitate studying human markers in mice. To test the hypothesis, we performed weighted gene co-expression analysis by integrating circulating miRNA and tumor gene expression profiles from individual mice and discovered hub miRNAs in highly correlated expression modules. We validated the hub miRNAs using F2 hybrid mice derived from radiogenic HCC susceptible and resistant founders and identified 38 circulating miRNA markers associated with radiation-induced HCC. Through literacy search, we selected 10 human HCC-associated circulating miRNAs that had been validated in multiple independent patient cohorts. Nine of the 10 human markers overlapped with the mouse hub miRNAs, indicating the feasibility of using mouse model to study human circulating HCC markers. Using serially collected plasma samples from irradiated mice, we studied the kinetics of circulating miRNAs. We found that the mouse plasma levels of 4 human circulating markers, miR-122-5p, miR-100-5p, miR-34a-5p and miR-365-3p increased linearly as the time approaching towards HCC detection, indicating the correlations of the 4 miRNAs with oncogenic progression. Estimation of change points in the kinetics of the 4 circulating miRNAs suggested the changes started months before HCC detection, ranging from 17.5 to 6.8 months. Our data demonstrated that the 4 circulating miRNAs were sensitive biomarkers potentially valuable for the screening of early stage HCC.
2022-07-06 | GSE196193 | GEO
Project description:The purpose of this experiment is to characterize the intratumor heterogeneity in liver cancer and to study the crosstalk between the immune component of the tumor and the aberrant hepatocites.
2020-01-16 | E-MTAB-5905 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of death worldwide. Due to latent liver disease, late diagnosis, and nonresponse to systemic treatments, surgical resection and/or biopsy specimens are still generally considered as the gold standard by clinicians for clinical decision-making until now. Since the conventional tissue biopsy is invasive and contains small tissue samples, it is unable to represent tumor heterogeneity or monitor dynamic tumor progression. Therefore, it is imperative to find a new less invasive or noninvasive diagnostic strategy to detect HCC at an early stage and to monitor HCC recurrence. Over the past years, a new diagnostic concept known as "liquid biopsy" has emerged with substantial attention. Liquid biopsy is noninvasive and allows repeated analyses to monitor tumor recurrence, metastasis or treatment responses in real time. With the advanced development of new molecular techniques, HCC circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) detection have achieved interesting and encouraging results. In this review, we focus on the clinical applications of CTCs and ctDNA as key components of liquid biopsy in HCC patients.
| S-EPMC6607541 | biostudies-literature
Project description:Single-cell RNA sequencing of circulating tumor cells in hepatocellular carcinoma
| PRJNA421273 | ENA
Project description:Circulating miRNA associated with hepatocellular carcinoma in mice
| PRJNA803878 | ENA
Project description:<p>Comprehensive analyses of cancer genomes in clinical settings promise to inform prognoses and guide the deployment of precise cancer treatments. A major barrier, however, is the inaccessibility of adequate metastatic tissue for accurate genomic analysis in prostate and other cancers. A potential solution is to characterize circulating tumor cells (CTCs), but this requires overcoming multiple technical hurdles. Here, we report an integrated process to isolate, qualify, and sequence whole exomes of CTCs with high fidelity, using a census-based sequencing strategy. Power calculations suggest that mapping of over 99.995% of the territory accessible in bulk exome sequencing is possible in CTCs. We validated our sequencing process in two prostate cancer patients including one for whom we compared CTC-derived mutations to mutations found in a lymph node metastasis and nine cores of the primary tumor. 51 of 73 CTC mutations (70%) were observed in matched tissue. Moreover, we identified 10 early trunk mutations and 56 metastatic trunk mutations in the non-CTC tumor samples and found 90% and 73% of these, respectively, in CTC exomes. This study establishes a foundation for CTC genomics in the clinic.</p>
| phs000717 | dbGaP
Project description:Somatic copy number alterations (SCNAs) are important genetic drivers of many cancers. We investigated the feasibility of obtaining SCNA profiles from circulating tumor cells (CTCs) as a molecular liquid biopsy for hepatocellular carcinoma (HCC). CTCs from ten HCC patients underwent SCNA profiling. The Cancer Genome Atlas (TCGA) SCNA data were used to develop a cancer origin classification model, which was then evaluated for classifying 44 CTCs from multiple cancer types. Sequencing of 18 CTC samples (median: 4 CTCs/sample) from 10 HCC patients using a low-resolution whole-genome sequencing strategy (median: 0.88 million reads/sample) revealed frequent SCNAs in previously reported HCC regions such as 8q amplifications and 17p deletions. SCNA profiling revealed that CTCs share a median of 80% concordance with the primary tumor. CTCs had SCNAs not seen in the primary tumor, some with prognostic implications. Using a SCNA profiling model, the tissue of origin was correctly identified for 32/44 (73%) CTCs from 12/16 (75%) patients with different cancer types.
| S-EPMC7331695 | biostudies-literature
Project description:Background and aimsCirculating tumor cells (CTCs) or circulating tumor DNA (ctDNA) may be used for diagnostic or prognostic purposes in patients with hepatocellular carcinoma (HCC). We aim to determine whether CTCs or ctDNA are suitable to determine oncogenic mutations in HCC patients.MethodsTwenty-six mostly advanced HCC patients were enrolled. 30 mL peripheral blood from each patient was obtained. CellSearch system was used for CTC detection. A sequencing panel covering 14 cancer-relevant genes was used to identify oncogenic mutations. TERT promoter C228T and C250T mutations were determined by droplet digital PCR.ResultsCTCs were detected in 27% (7/26) of subjects but at low numbers (median: 2 cells, range: 1-15 cells) and ctDNA in 77% (20/26) of patients. Mutations in ctDNA were identified in several genes: TERT promoter C228T (77%, 20/26), TP53 (23%, 6/26), CTNNB1 (12%, 3/26), PIK3CA (12%, 3/26) and NRAS (4%, 1/26). The TERT C228T mutation was present in all patients with one or more ctDNA mutations, or detectable CTCs. The TERT C228T and TP53 mutations detected in ctDNA were present at higher levels in matched primary HCC tumor tissue. The maximal variant allele frequency (VAF) of ctDNA was linearly correlated with largest tumor size and AFP level (Log10). CtDNA (or TERT C228T) positivity was associated with macrovascular invasion, and positivity of ctDNA (or TERT C228T) or CTCs (≥ 2) correlated with poor patient survival.ConclusionsOncogenic mutations could be detected in ctDNA from advanced HCC patients. CtDNA analysis may serve as a promising liquid biopsy to identify druggable mutations.
| S-EPMC8100622 | biostudies-literature