Dataset Information

Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy.

ABSTRACT: The aim of the present study was to analyze copy number variations (CNV) of multiple oncogenes and tumor suppressor genes in genomic DNA from primary tumor tissue, lymph node metastasis and cell-free DNA (cfDNA) from serum of 72 urothelial carcinoma of bladder (UCB) patients treated with radical cystectomy (RC), using multiplex ligation-dependent probe amplification (MLPA). We hypothesized that primary tumor and lymph node metastasis show similar CNV profiles, and CNV are more present in lymph node metastasis compared to primary tumor tissue. Samples from 43 (59.7%) patients could be analyzed. In total, 35 (83%), 26 (68%) and 8 (42%) patients had CNV in primary tumor, serum and lymph node metastasis, respectively. MYC, CCND1, ERBB2 and CCNE1 displayed the most frequent amplifications. In particular, CNV in ERBB2 was associated with aggressive tumor characteristics. CNV in both ERBB2 and TOP2A were risk factors for disease recurrence. The current findings show that CNV are present in various oncogenes and tumor suppressor genes in genomic DNA from primary tumor, lymph node metastasis and cfDNA from serum. CNV were more present in genomic DNA from primary tumor tissue compared to cfDNA from serum and genomic DNA from lymph node metastasis. Patients with CNV in ERBB2 and TOP2A are at increased risk for disease recurrence following RC. Further studies are necessary to validate, whether these genes may represent promising candidates for targeted-therapy.

SUBMITTER: Soave A

PROVIDER: S-EPMC7725833 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy.

Soave Armin A Kluwe Lan L Yu Hang H Rink Michael M Gild Philipp P Vetterlein Malte W MW Marks Philipp P Sauter Guido G Fisch Margit M Meyer Christian P CP Ludwig Tim T Dahlem Roland R Minner Sarah S Pantel Klaus K Steinbach Bettina B Schwarzenbach Heidi H

Scientific reports 20201209 1

The aim of the present study was to analyze copy number variations (CNV) of multiple oncogenes and tumor suppressor genes in genomic DNA from primary tumor tissue, lymph node metastasis and cell-free DNA (cfDNA) from serum of 72 urothelial carcinoma of bladder (UCB) patients treated with radical cystectomy (RC), using multiplex ligation-dependent probe amplification (MLPA). We hypothesized that primary tumor and lymph node metastasis show similar CNV profiles, and CNV are more present in lymph n ...[more]

PMID: 33298978

Similar Datasets

Project description:The number of lymph node dissections (LNDs) is an independent factor influencing the survival time of patients with bladder cancer (BCa) after radical resection (RC). The present study aimed to investigate the association between the number of LNDs and the survival of patients with BCa at different stages and who underwent RC in the United States of America and China. Records from 17,730 American patients with BCa and 158 Chinese patients with BCa were collected from the Surveillance, Epidemiology and End Results (SEER) and the Shanghai Tenth People's Hospital (China) databases, respectively. Kaplan-Meier curve and χ2 test were used to determine the overall survival time (OS) of patients with BCa. Cox regression analysis was used to analyze the effects of LND number on OS. Overall, 13,421 (75.7%) patients were negative for lymph node metastasis (N0) and 4,309 (24.3%) were positive for lymph node metastasis (N+) among the 17,730 American patients with BCa. In the group of 158 Chinese patients, 125 (79.1%) were N0 and 33 (20.9%) were N+. In the American patients, the median number of dissected nodes was 11.0 [interquartile range (IQR)=3.0-21.0] for N0 patients and 14.0 (IQR=8.0-23.0) for N+ patients. The median number of LNDs was 5.0 (IQR=2.0-7.0) for Chinese N0 patients and 5.0 (IQR=1.5-10.5) for Chinese N+ patients. The number of LNDs may therefore be an independent factor associated with survival in patients who underwent RC. Furthermore, a higher number of LNDs was associated with longer OS in patients with BCa [American patients, ≥13 nodes vs. ≤5 nodes, hazard ratio (HR)=0.62, 95% confidence interval (CI)=0.59-0.65, P<0.001; Chinese patients, ≥5 nodes vs. ≤1 node, HR=0.27, 95% CI=0.12-0.62, P=0.002]. The number of LNDs in patients with BCa and N+ was higher compared with number of LNDs in patients with BCa and N0 who underwent RC. More extensive LND improved the OS in both the patients from USA and China. Increasing the number of LNDs may therefore be crucial when treating patients with BCa.

Project description:BackgroundLymph node metastasis is an important indicator of oncologic outcome for patients with rectal cancer. Identifying predictive biomarkers of lymph node metastasis could therefore be clinically useful.ObjectiveThe aim of this study was to assess whether chromosomal copy number alterations can assist in predicting persistent lymph node metastasis in patients with locally advanced rectal cancer treated with preoperative chemoradiation therapy.DesignThis is a nonrandomized, prospective phase II study.SettingThis study took place in a multi-institutional setting.PatientsNinety-five patients with stage II (cT3-4, cN0) or stage III (any cT, cN1-2) rectal cancer were included.InterventionPatients were treated with preoperative chemoradiation therapy followed by total mesorectal excision. Pretreatment biopsy tumor DNA and surgical margin control DNA were extracted and analyzed by oligonucleotide array-based comparative genomic hybridization. Chromosomal copy number alterations were correlated with persistent lymph node metastasis. Finally, a model for predicting persistent lymph node metastasis was built.Main outcome measuresThe primary outcomes assessed were whether chromosomal copy number alterations are associated with persistent lymph node metastasis in patients with rectal cancer and the accuracy of oligonucleotide array-based comparative genomic hybridization for predicting lymph node metastasis.ResultsTwenty-five of 95 (26%) patients had lymph node metastasis after chemoradiation. Losses of 28 chromosomal regions, most notably in chromosome 4, were significantly associated with lymph node metastasis. Our predictive model contained 65 probes and predicted persistent lymph node metastasis with 68% sensitivity, 93% specificity, and positive and negative predictive values of 77% and 89%. The use of this model accurately predicted lymph node status (positive or negative) after chemoradiation therapy in 82 of 95 patients (86%).LimitationsThe patient cohort was not completely homogeneous, which may have influenced their clinical outcome. In addition, although we performed rigorous, statistically sound internal validation, external validation will be important to further corroborate our findings.ConclusionsCopy number alterations can help identify patients with rectal cancer who are at risk of lymph node metastasis after chemoradiation.

Dataset Information

Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy.

Publications

Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets