Hadano Naoto, Murakami Yoshiaki, Uemura Kenichiro, Hashimoto Yasusi, Kondo Naru, Nakagawa Naoya, Sueda Taijiro, Hiyama Eiso
Department of Surgery, Applied Life Sciences Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Natural Science Center for Basic Research and Development (N-BARD), Hiroshima University, Hiroshima, Japan.
Br J Cancer. 2016 Jun 28;115(1):59-65. doi: 10.1038/bjc.2016.175. Epub 2016 Jun 9.
Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed at an advanced stage, leading to a poor prognosis. Therefore, interest in the development of non-invasive biomarkers for prognostic prediction has grown rapidly. Here, we assessed the clinical implications of v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated circulating tumour DNA (ctDNA) as a useful surrogate biomarker in patients with resectable PDAC.
We used droplet digital polymerase chain reaction to detect rare mutant tumour-derived KRAS genes in plasma cell-free DNA (cfDNA) as ctDNA. Samples were collected from 105 patients who underwent pancreatoduodenectomy for PDAC at a single institution. Overall survival (OS) was analysed according to the presence of ctDNA.
Among the 105 cases, ctDNA was detected in 33 (31%) plasma samples. The median OS durations were 13.6 months for patients with ctDNA (ctDNA+) and 27.6 months for patients without ctDNA. Patients who were ctDNA+ had a significantly poorer prognosis with respect to OS (P<0.0001).
Our findings suggested that the presence of ctDNA in plasma samples could be an important and powerful predictor of poor survival in patients with PDAC. Accordingly, ctDNA detection might be a promising approach with respect to PDAC treatment.
胰腺导管腺癌(PDAC)常于晚期被诊断出来,导致预后较差。因此,对用于预后预测的非侵入性生物标志物的研究兴趣迅速增长。在此,我们评估了v-Ki-ras2 Kirsten大鼠肉瘤病毒癌基因同源物(KRAS)突变的循环肿瘤DNA(ctDNA)作为可切除PDAC患者有用替代生物标志物的临床意义。
我们使用液滴数字聚合酶链反应来检测血浆游离DNA(cfDNA)中作为ctDNA的罕见突变肿瘤来源的KRAS基因。样本取自一家机构中105例行胰十二指肠切除术治疗PDAC的患者。根据ctDNA的存在情况分析总生存期(OS)。
在105例病例中,33份(31%)血浆样本中检测到ctDNA。ctDNA阳性(ctDNA+)患者的中位OS持续时间为13.6个月,ctDNA阴性患者为27.6个月。ctDNA+患者的OS预后明显较差(P<0.0001)。
我们的研究结果表明,血浆样本中ctDNA的存在可能是PDAC患者生存不良的重要且有力的预测指标。因此,ctDNA检测对于PDAC治疗可能是一种有前景的方法。