Thongyoo Pitchasak, Chindaprasirt Jarin, Aphivatanasiri Chaiwat, Intarawichian Piyapharom, Kunprom Waritta, Kongpetch Sarinya, Techasen Anchalee, Loilome Watcharin, Namwat Nisana, Titapun Attapol, Jusakul Apinya
Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
Medical Oncology Program, Department of Internal Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Cancer Genomics Proteomics. 2025 Jan-Feb;22(1):112-126. doi: 10.21873/cgp.20492.
BACKGROUND/AIM: Cholangiocarcinoma (CCA) is an aggressive hepatobiliary malignancy characterized by genomic heterogeneity. KRAS mutations play a significant role in influencing patient prognosis and guiding therapeutic decision-making. This study aimed to determine the prevalence and prognostic significance of KRAS mutations in CCA, asses the detection of KRAS G12/G13 mutations in plasma cell-free DNA (cfDNA), and evaluate the prognostic value of KRAS G12/G13 mutant allele frequency (MAF) in cfDNA in relation to clinicopathological data and patient survival.
A retrospective analysis of 937 CCA patients was performed using data from cBioPortal to examine KRAS mutation profiles and their association with survival. Plasma from 101 CCA patients was analyzed for KRAS G12/G13 mutations in the cfDNA using droplet digital PCR, and the results were compared with tissue-based sequencing from 78 matched samples.
KRAS driver mutations were found in 15.6% of patients, with common variants being G12D (37.0%), G12V (24.0%) and Q61H (8.2%). Patients harboring KRAS mutations exhibited decreased overall and recurrence-free survival. KRAS G12/G13 mutations were detected in 14.9% of cfDNA samples, showing moderate concordance with tissue sequencing, and achieving 80% sensitivity and 93% specificity. Elevated KRAS G12/G13 MAF in cfDNA, combined with high CA19-9 levels, correlated with poorer survival outcomes.
The presence of KRAS mutations was associated with poor survival in CCA, underscoring the importance of KRAS mutations as prognostic markers. The detection of KRAS mutations in cfDNA demonstrated potential as a promising non-invasive alternative for mutation detection and, when combined with CA19-9 levels, may improve prognostic efficacy in CCA.
背景/目的：胆管癌（CCA）是一种侵袭性肝胆恶性肿瘤，具有基因组异质性。KRAS突变在影响患者预后和指导治疗决策方面起着重要作用。本研究旨在确定CCA中KRAS突变的发生率和预后意义，评估血浆游离DNA（cfDNA）中KRAS G12/G13突变的检测情况，并评估cfDNA中KRAS G12/G13突变等位基因频率（MAF）与临床病理数据及患者生存的预后价值。
利用cBioPortal的数据对937例CCA患者进行回顾性分析，以检查KRAS突变谱及其与生存的关联。采用液滴数字PCR分析101例CCA患者血浆cfDNA中的KRAS G12/G13突变，并将结果与78例匹配样本的组织测序结果进行比较。
15.6%的患者存在KRAS驱动突变，常见变异为G12D（37.0%）、G12V（24.0%）和Q61H（8.2%）。携带KRAS突变的患者总生存期和无复发生存期降低。14.9%的cfDNA样本检测到KRAS G12/G13突变，与组织测序显示出中等一致性，敏感性达80%，特异性达93%。cfDNA中KRAS G12/G13 MAF升高，联合高CA19-9水平，与较差的生存结果相关。
KRAS突变的存在与CCA患者的不良生存相关，强调了KRAS突变作为预后标志物的重要性。cfDNA中KRAS突变的检测显示出作为一种有前景的非侵入性突变检测替代方法的潜力，并且与CA19-9水平联合使用时，可能提高CCA的预后疗效。
