• Chromosomal instability
• Microbiome
• Molecular subtype
• Pancreatic cancer

• Humans
• Pancreatic Neoplasms/microbiology
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/mortality
• Chromosomal Instability
• Male
• Female
• Middle Aged
• Aged
• Prognosis
• Microbiota
• Whole Genome Sequencing

• Adjuvant therapy
• Application prospects
• Gastric cancer
• Molecular typing
• Precancerous lesions of gastric cancer
• Ultrasensitive chromosomal aneuploidy detection

• Humans
• Retrospective Studies
• Pancreas/pathology
• Pancreatic Neoplasms/surgery
• Pancreatic Cyst/genetics
• Pancreatic Cyst/diagnosis
• Cystadenoma, Serous/genetics
• Cystadenoma, Serous/diagnosis
• Cystadenoma, Serous/pathology
• Genomics

• 2019YFC1315800/2019YFC1315802 the National Key Research & Development Program
• SZSM201601070 Sanming Project of Medicine in Shenzhen
• 82273338 the National Natural Science Foundation of China
• U20A20378 the National Natural Science Foundation of China
• 2021C03063 Zhejiang Provincial Key Research & Development Program
• LTGY23H160005 Zhejiang Provincial Natural Science Foundation of China

• Chromosomal instability (CIN)
• Gliomas
• Low-coverage whole-genome sequencing (LC-WGS)
• Molecular pathology
• Ultrasensitive copy number aberration detector (UCAD)

• Humans
• Cost-Benefit Analysis
• Glioma/genetics
• Glioma/pathology
• Chromosomal Instability
• Risk Assessment

Non-invasive, especially the urine-based diagnosis of prostate cancer (PCa) remains challenging. Although prostate cancer antigen (PSA) is widely used in prostate cancer screening, the false positives may result in unnecessary invasive procedures. PSA elevated patients are triaged to further evaluation of free/total PSA ratio (f/t PSA), to find out potential clinically significant PCa before undergoing invasive procedures. Genomic instability, especially chromosomal copy number variations (CNVs) were proved much more tumor specific. Here we performed a prospective study to evaluate the diagnostic value of CNV via urine-exfoliated cell DNA analysis in PCa.

We enrolled 28 PSA elevated patients (≥ 4 ng/ml), including 16 PCa, 9 benign prostate hypertrophy (BPH) and 3 prostatic intraepithelial neoplasia (PIN). Fresh initial portion urine was collected after hospital admission. Urine exfoliated cell DNA was analyzed by low coverage Whole Genome Sequencing, followed by CNV genotyping by the prostate cancer chromosomal aneuploidy detector (ProCAD). CNVs were quantified in absolute z-score (|Z|). Serum free/total PSA ratio (f/t PSA) was reported altogether.

In patients with PCa, the most frequent CNV events were chr3q gain (n = 2), chr8q gain (n = 2), chr2q loss (n = 4), and chr18q loss (n = 3). CNVs were found in 81.2% (95% Confidence Interval (CI) 53.7–95.0%) PCa. No CNV was identified in BPH patients. A diagnosis model was established by incorporating all CNVs. At the optimal cutoff of |Z|≥ 2.50, the model reached an AUC of 0.91 (95% CI 0.83–0.99), a sensitivity of 81.2% and a specificity of 100%. The CNV approach significantly outperformed f/t PSA (AUC = 0.62, P = 0.012). Further analyses showed that the CNV positive rate was significantly correlated with tumor grade. CNVs were found in 90.9% (95% CI 57.1–99.5%) high grade tumors and 60.0% (95% CI 17.0–92.7%) low grade tumors. No statistical significance was found for patient age, BMI, disease history and family history.

Urine exfoliated cells harbor enriched CNV features in PCa patients. Urine detection of CNV might be a biomarker for PCa diagnosis, especially in terms of the clinically significant high-grade tumors.

The online version contains supplementary material available at 10.1186/s12920-022-01253-5.

We present a case of a 43-year-old man with advanced hepatocellular carcinoma (HCC) with portal vein tumour thrombus. Initially, transcatheter arterial chemoembolization (TACE) was performed. Although alpha-fetoprotein (AFP) levels decreased, circulating tumour DNA (ctDNA) levels showed an upward trend, and abdominal magnetic resonance imaging (MRI) showed that tumours in the portal vein had increased. Based on ctDNA profiling, apatinib and anti-programmed cell death protein 1 (anti-PD-1) antibodies and were sequentially administered. Approximately three months later, intrahepatic tumours had significantly diminished and AFP and ctDNA levels had reduced. The response was sustained at the 23-month follow-up and the patient was in good health. Combination treatment of TACE, apatinib and anti-PD-1 antibodies was effective, and profiling of ctDNA fragmentation may be beneficial in the therapeutic management of patients with HCC.

• Hepatocellular carcinoma
• anti-PD-1 antibody
• apatinib
• circulating tumour DNA
• transcatheter arterial chemoembolization

To characterize plasma cell‐free cancer genome chromosomal instabilities (CIN) in patients with liver cancer and to evaluate the potential of CIN as minimally invasive biomarkers for primary liver cancer (PLC) diagnoses.

We collected 196 plasma samples from 172 individuals in two cohorts, a discovery cohort of surgery ineligible PLC patients and a validation cohort of hepatectomy patients with pathological disease confirmations. All samples were subjected to HiSeq X10 sequencing followed by a customized bioinformatics workflow Ultrasensitive Chromosome Aneuploidy Detection (UCAD).

In the discovery cohort, 29 significant copy number changes were identified in plasma from surgery‐ineligible PLC. Twenty‐two (95.7%) surgery‐ineligible liver cancers were identified as harboring copy number changes in at least 1 of 29 segments. Meanwhile 40/41 (97.6%) noncancers harbored no changes. In the validation cohort, 54 (69.4%) surgery‐eligible liver cancers were identified with positive screening, all of which were subsequently confirmed as cancer by pathological examination. Moreover, 26/27 = 96.3% noncancers were identified with negative screening. UCAD‐positive screening was significantly associated with microvascular invasion (OR > 10, 95% CI:[2.53,]), tumor stages B and C (OR = 8.59, 95% CI [1.07, 400]), and tumor size ≥ 3 cm (OR = 5.68, 95% CI [1.43, 28.1]). Furthermore, we collected 29 followed‐up plasma samples from 19 postsurgery patients. Nine (31.0%) postsurgery samples from 6 (31.5%) patients were identified with positive screening. Among them, 3 patients (50.0%) with positive screening were then confirmed as having disease recurrences.

In addition to AFP, plasma cell‐free DNA sequencing is a useful tool for primary liver cancer diagnoses.

• Cell-Free DNA
• Chromosomal Instability
• Primary Liver Cancer