Hata Tatsuo, Mizuma Masamichi, Masuda Kunihiro, Chiba Kazuharu, Ishida Masaharu, Ohtsuka Hideo, Nakagawa Kei, Morikawa Takanori, Kamei Takashi, Unno Michiaki
Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Ann Surg Oncol. 2021 Apr;28(4):2235-2245. doi: 10.1245/s10434-020-09440-3. Epub 2021 Jan 3.
Some presumed resectable pancreatic cancer patients harbor radiographically occult metastases that are incidentally identified at the time of abdominal exploration. This study aims to identify novel diagnostic or predictive microRNA (miRNA) markers for subclinical peritoneal dissemination in patients with pancreatic cancer undergoing abdominal exploration.
Peritoneal lavage fluid samples were harvested from 74 patients with pancreatic cancer at the time of staging laparoscopy. Microarray analysis was performed using peritoneal lavage fluids with positive and negative cytology. Candidate microRNA expression was quantified and validated by droplet-digital PCR assays.
In the miRNA array analysis, miR-593-3p showed significant upregulation in peritoneal lavage fluids with positive cytology. Of the 74 patients validated, peritoneal lavage fluids with positive cytology had significantly higher expression of miR-593-3p than those with negative cytology (P < 0.001). Even in cases with no peritoneal dissemination and negative cytology, multivariate analysis revealed that elevated miR-593-3p expression was significantly correlated with worse overall survival than those with low expression (hazard ratio: 3.474, P = 0.042). Of the 48 patients who underwent pancreatectomy, multivariate analysis also demonstrated that higher expression of miR-593-3p in peritoneal lavage was the only significant poor prognostic marker influencing both overall survival (hazard ratio: 23.38, P = 0.005) and recurrence-free survival (hazard ratio: 5.700, P = 0.002).
Elevated miR-593-3p expression in peritoneal lavage suggests the presence of subclinical micrometastasis even in cases with localized pancreatic cancer, and miR-593-3p could be a useful prognostic predictor for pancreatic cancer patients undergoing staging laparoscopy.
一些推测可切除的胰腺癌患者存在影像学隐匿性转移，这些转移在腹部探查时被偶然发现。本研究旨在为接受腹部探查的胰腺癌患者亚临床腹膜播散识别新的诊断或预测性微小RNA（miRNA）标志物。
在分期腹腔镜检查时从74例胰腺癌患者中采集腹腔灌洗液样本。对细胞学阳性和阴性的腹腔灌洗液进行微阵列分析。通过液滴数字PCR测定法对候选微小RNA表达进行定量和验证。
在miRNA阵列分析中，miR-593-3p在细胞学阳性的腹腔灌洗液中显示出显著上调。在74例经过验证的患者中，细胞学阳性的腹腔灌洗液中miR-593-3p的表达明显高于细胞学阴性的腹腔灌洗液（P < 0.001）。即使在无腹膜播散且细胞学阴性的病例中，多变量分析显示，miR-593-3p表达升高与低表达患者相比，总生存期更差显著相关（风险比：3.474，P = 0.042）。在48例行胰腺切除术的患者中，多变量分析还表明，腹腔灌洗中miR-593-3p较高表达是影响总生存期（风险比：23.38，P = 0.005）和无复发生存期（风险比：5.700，P = 0.002）的唯一显著不良预后标志物。
腹腔灌洗中miR-593-3p表达升高表明即使在局限性胰腺癌病例中也存在亚临床微转移，并且miR-593-3p可能是接受分期腹腔镜检查的胰腺癌患者有用的预后预测指标。
