Prediction System for KRAS Mutation Detection in Circulating Tumor DNA in Unresectable Pancreatic Cancer.

IF 1.7 4区医学 Q4 ONCOLOGY

Anticancer research Pub Date : 2025-09-01 DOI:10.21873/anticanres.17751

Hiroshi Shimizu, Rei Suzuki, Hiroyuki Asama, Mitsuru Sugimoto, Kentaro Sato, Kento Osawa, Rei Ohira, Hiromasa Ohira

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引用次数: 0

Abstract

Background/aim: Unresectable pancreatic cancer (PC) is an aggressive malignancy with a poor prognosis and limited treatment options. Advances in molecular profiling and liquid biopsy, specifically the detection of circulating tumor DNA (ctDNA), offer new avenues for personalized therapy. KRAS mutations are present in approximately 63-70% of PC patients in circulating cell free DNA in the blood of approximately 63-70% of patients with PC; however, their detection via liquid biopsy can be influenced by disease stage, metastasis site, and ctDNA concentration. The aim of this retrospective study was to develop a prediction model for KRAS mutation detection in unresectable patients with PC using clinical variables.

Patients and methods: We retrospectively analyzed 32 patients who underwent ctDNA testing from 2019 to 2024, utilizing either FoundationOne^® Liquid CDx or Guardant360^® CDx panels. Multivariate analysis of the clinical factors was performed via logistic regression with stepwise selection to elucidate independent predictors of KRAS mutation detection. A nomogram was developed based on the independent predictors of successful KRAS detection.

Results: Multivariate analysis revealed that liver metastasis, multiple metastatic sites, and disease progression were significant predictors of successful KRAS mutation detection. A nomogram and the receiver operating characteristic curve demonstrated high predictive accuracy, with a sensitivity of 70%, specificity of 90.9%, and area under curve of 0.83.

Conclusion: Our prediction system effectively stratified patients by the likelihood of KRAS mutation detection, offering a practical tool for selecting candidates for liquid biopsy. These findings underscore the importance of personalized approaches in unresectable PC management and suggest that patients without these key clinical factors may not benefit from ctDNA testing. Future studies should validate this model in larger cohorts.

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不可切除胰腺癌循环肿瘤DNA KRAS突变检测预测系统。

背景/目的：不可切除胰腺癌（PC）是一种侵袭性恶性肿瘤，预后差，治疗选择有限。分子分析和液体活检技术的进步，特别是循环肿瘤DNA （ctDNA）的检测，为个性化治疗提供了新的途径。大约63-70%的PC患者血液中循环游离细胞DNA中存在KRAS突变；然而，通过液体活检检测它们可能受到疾病分期、转移部位和ctDNA浓度的影响。本回顾性研究的目的是利用临床变量建立一种预测模型，用于无法切除的PC患者的KRAS突变检测。患者和方法：我们回顾性分析了从2019年到2024年接受ctDNA检测的32例患者，使用FoundationOne®Liquid CDx或guarant360®CDx面板。通过logistic回归和逐步选择对临床因素进行多因素分析，以阐明KRAS突变检测的独立预测因素。基于成功检测KRAS的独立预测因子，建立了一个nomogram。结果：多因素分析显示，肝转移、多转移部位和疾病进展是KRAS突变检测成功的重要预测因素。nomogram和receiver operating characteristic curve具有较高的预测准确度，灵敏度为70%，特异度为90.9%，曲线下面积为0.83。结论：我们的预测系统通过KRAS突变检测的可能性有效地对患者进行分层，为选择液体活检候选人提供了实用的工具。这些发现强调了在不可切除的PC治疗中个性化方法的重要性，并提示没有这些关键临床因素的患者可能无法从ctDNA检测中获益。未来的研究应在更大的队列中验证该模型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.