Dataset Information

Hypermethylated SHOX2 in circulating cell-free DNA post renal cell carcinoma surgery as TNM-independent biomarker for recurrence risk.

ABSTRACT:

Introduction

Adjuvant immune checkpoint inhibitor trials in renal cell carcinoma (RCC) call for improved recurrence risk stratification. Due to limitations of circulating tumor DNA (ctDNA) use in RCC, the use of hypermethylated SHOX2 gene (mSHOX2) in circulating cell-free DNA is explored as a surrogate marker for identifying high-risk patients after RCC surgery.

Methods

Liquid biopsies were collected post-surgery from 45 RCC patients (mean duration 4.3 days). Real-time polymerase chain reaction was used to analyze SHOX2 methylation in circulating cell-free DNA. Patients were categorized as mSHOX2 positive or negative by cut-off. Metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were assessed using Cox regression and Log-rank analyses (median follow-up time: 60 months).

Results

17 patients were mSHOX2 positive, showing unfavorable OS/CSS (Log-rank P = 0.004 and 0.02) and nearly 6-fold higher recurrence risk (hazard ratio 5.89, 95% CI 1.46-23.8). Multivariable Cox analysis confirmed mSHOX2 as an independent recurrence risk factor, disregarding TNM-based stratification.

Conclusions

mSHOX2 effectively identifies high-risk RCC patients post-surgery, indicating minimal residual disease. This easy to implement biomarker has potential for guiding of adjuvant therapy decisions.

SUBMITTER: Buttner T

PROVIDER: S-EPMC10839385 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hypermethylated SHOX2 in circulating cell-free DNA post renal cell carcinoma surgery as TNM-independent biomarker for recurrence risk.

Büttner Thomas T Zarbl Romina R Krausewitz Philipp P Strieth Sebastian S Kristiansen Glen G Eckstein Markus M Ralser Damian J DJ Hölzel Michael M Ritter Manuel M Ellinger Jörg J Dietrich Dimo D Klümper Niklas N

American journal of translational research 20240115 1

<h4>Introduction</h4>Adjuvant immune checkpoint inhibitor trials in renal cell carcinoma (RCC) call for improved recurrence risk stratification. Due to limitations of circulating tumor DNA (ctDNA) use in RCC, the use of hypermethylated SHOX2 gene (mSHOX2) in circulating cell-free DNA is explored as a surrogate marker for identifying high-risk patients after RCC surgery.<h4>Methods</h4>Liquid biopsies were collected post-surgery from 45 RCC patients (mean duration 4.3 days). Real-time polymerase ...[more]

PMID: 38322559

Similar Datasets

Project description:BackgroundDiffuse gliomas, grades II and III, hereafter called lower-grade gliomas (LGG), have variable, difficult to predict clinical courses, resulting in multiple studies to identify prognostic biomarkers. The purpose of this study was to assess expression or methylation of the homeobox family gene SHOX2 as independent markers for LGG survival.MethodsWe downloaded publically available glioma datasets for gene expression and methylation. The Cancer Genome Atlas (TCGA) (LGG, n=516) was used as a training set, and three other expression datasets (n=308) and three other methylation datasets (n=320), were used for validation. We performed Kaplan-Meier survival curves and univariate and multivariate Cox regression model analyses.FindingsSHOX2 expression and gene body methylation varied among LGG patients and highly significantly predicted poor overall survival. While they were tightly correlated, SHOX2 expression appeared more potent as a prognostic marker and was used for most further studies. The SHOX2 prognostic roles were maintained after analyses by histology subtypes or tumor grade. We found that the combination of SHOX2 expression and IDH genotype status identified a subset of LGG patients with IDH wild-type (IDHwt) and low SHOX2 expression with considerably favorable survival. We further investigated the combination of SHOX2 with other known clinically relevant markers of LGG (TERT expression, 1p/19q chromosome co-deletion, MGMT methylation, ATRX mutation and NES expression). When combined with SHOX2 expression, we identified subsets of LGG patients with significantly favorable survival outcomes, especially in the subgroup with worse prognosis for each individual marker. Finally, multivariate analysis demonstrated that SHOX2 was a potent independent survival marker.InterpretationWe have identified that SHOX2 expression or methylation are potent independent prognostic indicators for predicting LGG patient survival, and have potential to identify an important subset of LGG patients with IDHwt status with significantly better overall survival. The combination of IDH or other relevant markers with SHOX2 identified LGG subsets with significantly different survival outcomes, and further understanding of these subsets may benefit therapeutic target identification and therapy selections for glioma patients.

Project description:BackgroundRecently, an in vivo study demonstrated that circulating tumor cell-associated white blood cell (CTC-WBC) cluster possess much greater potential than single CTCs. We aim to explore the correlation between the CTC-WBC cluster and the clinicopathological characteristics of hepatocellular carcinoma (HCC) patients to seek novel biomarkers for HCC metastasis and recurrence.MethodsWe retrospectively analyzed 136 HCC patients from October 2014 to March 2020 who received CTC tests using the CanPatrol CTC enrichment technique. The correlation between the clinical features and total CTCs, EMT-CTCs, and CTC-WBC cluster were analyzed by a chi-square test. The ROC curves were simulated for evaluating the diagnostic performance of CTC parameters in HCC metastasis. Patients were followed up from February 2015 to November 2021, and the relapse-free survival (RFS) was analyzed using the Kaplan-Meier curve.ResultsA total of 93.4% (127/136) and 31.6% (43/136) of HCC patients had detectable CTCs and CTC-WBC clusters. Baseline CTC-WBC cluster was closely correlated with microvascular invasion, portal vein tumor thrombus, and extrahepatic metastasis in pre-treatment HCC patients (P <0.05). The simulated ROC curves presented an AUC of 0.821 for the CTC-WBC cluster (sensitivity of 90.0% and specificity of 93.7%) in discriminating metastasis from non-metastatic HCC, which was higher than that for total CTCs (0.718) and EMT-CTCs (0.716). Further follow-up analysis showed that compared to the CTC-WBC cluster negative group (<1/5 ml), patients in the CTC-WBC cluster positive group (≥1/5 ml) presented an increased relapse ratio (60.0% versus 17.9%) and shorter RFS (22.9 versus 53.8 months). Dynamic analysis of CTCs parameters showed that total CTC level, EMT-CTCs proportion, and CTC-WBC cluster were decreased after microwave ablation treatment, while CTC-WBC cluster increased on average 10 months in advance of imaging (MRI) diagnosed recurrence.ConclusionThe CTC-WBC cluster is a promising biomarker for the metastasis diagnosis and prognosis of HCC metastasis. Dynamic monitoring of the CTC-WBC cluster is an effective method for early detection and intervention of HCC recurrence and metastasis.

Dataset Information

Hypermethylated SHOX2 in circulating cell-free DNA post renal cell carcinoma surgery as TNM-independent biomarker for recurrence risk.

Introduction

Methods

Results

Conclusions

Publications

Hypermethylated SHOX2 in circulating cell-free DNA post renal cell carcinoma surgery as TNM-independent biomarker for recurrence risk.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets