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KRAS 基因突变循环肿瘤 DNA 确定的 CA19-9 最佳值有助于预测胰腺癌患者的预后。

Optimal value of CA19-9 determined by KRAS-mutated circulating tumor DNA contributes to the prediction of prognosis in pancreatic cancer patients.

机构信息

Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan.

Nerima Hikarigaoka Hospital, 2-11-1, Hikarigaoka, Nerima-ku, Tokyo, 179-0072, Japan.

出版信息

Sci Rep. 2021 Oct 21;11(1):20797. doi: 10.1038/s41598-021-00060-9.

Abstract

Despite the acceptance of carbohydrate antigen 19-9 (CA19-9) as a valuable predictor for the prognosis of pancreatic ductal adenocarcinoma (PDAC), its cutoff value remains controversial. Our previous study showed a significant correlation between CA19-9 levels and the presence of KRAS-mutated ctDNA in the blood of patients with PDAC. Based on this correlation, we investigated the optimal cutoff value of CA19-9 before surgery. Continuous CA19-9 values and KRAS-mutated ctDNAs were monitored in 22 patients with unresectable PDAC who underwent chemotherapy between 2015 and 2017. Receiver operating characteristic curve analysis identified 949.7 U/mL of CA19-9 as the cutoff value corresponding to the presence of KRAS-mutated ctDNA. The median value of CA19-9 was 221.1 U/mL. Subsequently, these values were verified for their prognostic values of recurrence-free survival (RFS) and overall survival (OS) in 60 patients who underwent surgery between 2005 and 2013. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for OS and RFS in these patients (P = 0.001 and P = 0.010, respectively), along with lymph node metastasis (P = 0.008 and P = 0.017), unlike the median CA19-9 level (P = 0.150 and P = 0.210). The optimal CA19-9 level contributes to the prediction of prognosis in patients with PDAC before surgery.

摘要

尽管肿瘤相关抗原 19-9(CA19-9)被认为是预测胰腺导管腺癌(PDAC)预后的有价值指标,但它的截断值仍存在争议。我们之前的研究表明,CA19-9 水平与 PDAC 患者血液中 KRAS 突变 ctDNA 的存在之间存在显著相关性。基于这种相关性,我们研究了术前 CA19-9 的最佳截断值。我们监测了 2015 年至 2017 年期间接受化疗的 22 例不可切除 PDAC 患者的连续 CA19-9 值和 KRAS 突变 ctDNA。受试者工作特征曲线分析确定 CA19-9 的 949.7 U/mL 为截断值,对应于 KRAS 突变 ctDNA 的存在。CA19-9 的中位数为 221.1 U/mL。随后,我们在 2005 年至 2013 年间接受手术的 60 例患者中验证了这些值对无复发生存(RFS)和总生存(OS)的预后价值。多变量分析显示,949.7 U/mL 的 CA19-9 是这些患者 OS 和 RFS 的独立危险因素(分别为 P=0.001 和 P=0.010),与淋巴结转移(P=0.008 和 P=0.017)一样,但与中位数 CA19-9 水平(P=0.150 和 P=0.210)不同。最佳 CA19-9 水平有助于预测手术前 PDAC 患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1ad/8531317/b9e4e2738489/41598_2021_60_Fig1_HTML.jpg

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