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The prognostic value of KRAS mutation by cell-free DNA in cancer patients: A systematic review and meta-analysis.

ABSTRACT: KRAS mutation has been found in various types of cancer. However, the prognostic value of KRAS mutation in cell-free DNA (cfDNA) in cancer patients was conflicting. In the present study, a meta-analysis was conducted to clarify its prognostic significance. Literature searches of Cochrane Library, EMBASE, PubMed and Web of Science were performed to identify studies related to KRAS mutation detected by cfDNA and survival in cancer patients. Two evaluators reviewed and extracted the information independently. Review Manager 5.3 software was used to perform the statistical analysis. Thirty studies were included in the present meta-analysis. Our analysis showed that KRAS mutation in cfDNA was associated with a poorer survival in cancer patients for overall survival (OS, HR 2.02, 95% CI 1.63-2.51, P<0.01) and progression-free survival (PFS, HR 1.64, 95% CI 1.27-2.13, P<0.01). In subgroup analyses, KRAS mutation in pancreatic cancer, colorectal cancer, non-small cell lung cancer and ovarian epithelial cancer had HRs of 2.81 (95% CI 1.83-4.30, P<0.01), 1.67 (95% CI 1.25-2.42, P<0.01), 1.64 (95% CI 1.13-2.39, P = 0.01) and 2.17 (95% 1.12-4.21, p = 0.02) for OS, respectively. In addition, the ethnicity didn't influence the prognostic value of KRAS mutation in cfDNA in cancer patients (p = 0.39). Prognostic value of KRAS mutation was slightly higher in plasma than in serum (HR 2.13 vs 1.65), but no difference was observed (p = 0.37). Briefly, KRAS mutation in cfDNA was a survival prognostic biomarker in cancer patients. Its prognostic value was different in various types of cancer.

SUBMITTER: Zhuang R

PROVIDER: S-EPMC5552123 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The prognostic value of KRAS mutation by cell-free DNA in cancer patients: A systematic review and meta-analysis.

Zhuang Rongyuan R Li Song S Li Qian Q Guo Xi X Shen Feng F Sun Hong H Liu Tianshu T

PloS one 20170810 8

KRAS mutation has been found in various types of cancer. However, the prognostic value of KRAS mutation in cell-free DNA (cfDNA) in cancer patients was conflicting. In the present study, a meta-analysis was conducted to clarify its prognostic significance. Literature searches of Cochrane Library, EMBASE, PubMed and Web of Science were performed to identify studies related to KRAS mutation detected by cfDNA and survival in cancer patients. Two evaluators reviewed and extracted the information ind ...[more]

PMID: 28796802

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Project description:ObjectiveBy virtue of largely disparate clinical outcomes of prostate cancer (PCA), there is a pressing need to search for useful biomarkers for PCA prognosis. Cell-free DNA (cfDNA) is a promising biomarker for detecting, monitoring, and predicting survival of prostate cancer (PCA). However, the utility of total cfDNA quantitation in PCA in clinical setting remains elusive. Here, we performed a thorough meta-analysis to assess the prognostic value of cfDNA concentration for patients with PCA. In addition, we tested the possibility of the combination of PSA and cfDNA test results to improve the prediction power in PCA prognosis.Method and materialsMore than six databases, including PubMed, Web of Science, Medline, PMC, EMBASE and the Cochrane Library were searched. Results yielded all eligible articles from the date of inception to June 30, 2020. Continuous, diagnostic, and prognostic variables in cfDNA in PCA were included in the meta-analysis by STATA.ResultsA total of 23 articles were enrolled in our meta-analysis: 69.6% (16/23) were related to diagnosis, and 56.5% (13/23) were related to prognosis. The pooled concentration of cfDNA in PCA patients was significantly higher than in the control group (SMD = 0.89, 95%CI = 0.53, 1.26), mirroring results for the prostate-specific antigen (PSA). For the detection test variables, the SROC with 95%CI was 0.87 (0.84-0.90) for cfDNA concentration. In terms of prognostic variables, the concentrations of cfDNA were significantly related with progression-free survival (PFS, logHR = 0.84 (95%CI0.39, 1.28) and overall survival [OS, log HR = 0.60 (95%CI0.29, 0.90)]. Lastly, the test showed no significant publication bias in the present meta-analysis, excluding the diagnostic meta-analysis.ConclusionsThe concentration of cell-free DNA is high in the prostate cancer patients. The present study substantiates the prognostic value of the cfDNA concentration. High concentration cfDNA correlates with poor disease outcome of CRPC. The study cohort with large sample size is needed to evaluate the prognosis value of cfDNA in the future. We also emphasized that combination of PSA and cf DNA quantitation is important in future large individual meta study.

Project description:IntroductionBefore anti-EGFR therapy is given to patients with colorectal cancer, it is required to determine KRAS mutation status in tumor. When tumor tissue is not available, cell-free DNA (liquid biopsy) is commonly used as an alternative. Due to the low abundance of tumor-derived DNA in cell-free DNA samples, methods with high sensitivity were preferred, including digital polymerase chain reaction, amplification refractory mutation system and next-generation sequencing. The aim of this systemic review and meta-analysis was to investigate the accuracy of those methods in detecting KRAS mutation in cell-free DNA sample from patients with colorectal cancer.MethodsLiterature search was performed in Pubmed, Embase, and Cochrane Library. After removing duplicates from the 170 publications found by literature search, eligible studies were identified using pre-defined criteria. Quality of the publications and relevant data were assessed and extracted thereafter. Meta-DiSc and STATA softwares were used to pool the accuracy parameters from the extracted data.ResultsA total of 33 eligible studies were identified for this systemic review and meta-analysis. After pooling, the overall sensitivity, specificity, and diagnostic odds ratio were 0.77 (95%CI: 0.74-0.79), 0.87 (95%CI: 0.85-0.89), and 23.96 (95%CI: 13.72-41.84), respectively. The overall positive and negative likelihood ratios were 5.55 (95%CI: 3.76-8.19) and 0.29 (95%CI: 0.21-0.38), respectively. Area under curve of the summarized ROC curve was 0.8992.ConclusionDigital polymerase chain reaction, amplification refractory mutation system, and next-generation sequencing had overall high accuracy in detecting KRAS mutation in cell-free DNA sample. Large prospective randomized clinical trials are needed to further convince the accuracy and usefulness of KRAS mutation detection using cfDNA/liquid biopsy samples in clinical practice.Trial registrationPROSPERO CRD42020176682; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176682.

Dataset Information

The prognostic value of KRAS mutation by cell-free DNA in cancer patients: A systematic review and meta-analysis.

Publications

The prognostic value of KRAS mutation by cell-free DNA in cancer patients: A systematic review and meta-analysis.

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