Departament of medical oncology, National Cancer Institute, Santariskiu 1, 08660, Vilnius, LT, Lithuania.
Laboratory of Molecular Oncology, National Cancer Institute, Vilnius, Lithuania.
BMC Cancer. 2017 Sep 1;17(1):607. doi: 10.1186/s12885-017-3575-z.
MiRNAs are often deregulated in colorectal cancer and might function as tumor suppressors or as oncogenes. They participate in controlling key signaling pathways involved in proliferation, invasion and apoptosis and may serve as prognostic and predictive markers. In this study we aimed to evaluate the role of miRNA-148a and miRNA-625-3p in metastatic colorectal cancer.
Fifty-four patients with a first-time diagnosed CRC receiving FOLFOX ± Bevacizumab were involved in the study. Tumor samples underwent routine pathology examination including evaluation for tumor budding and KRAS. MiRNA-148a and miRNA-625-3p expression analysis was done by RT-PCR. Associations between expression of both miRNAs and clinico-pathological factors, treatment outcomes and survival were analyzed.
Both miRNA-148a and miRNA-625-3p were down-regulated in the tumors compared to normal colonic mucosa. Significantly lower expression of both miRNAs was noticed in tumors with budding phenomenon compared to tumors without it (median values of miRNA-148a were 0.314 and 0.753 respectively, p = 0.011, and 0.404 and 0.620 respectively for miRNA-625-3p, p = 0.036). Significantly lower expression of miRNA-625-3p was detected in rectal tumors, compared to tumors in the colon (median 0.390 and 0.665 respectively, p = 0.037). Progression free survival was significantly lower in patients with high miRNA-148a expression (6 and 9 months respectively, p = 0.033), but there were no significant differences in PFS for miRNA-625-3p and in overall survival for both miRNAs.
There was a significant relationship between low miRNA-148a and miRNA-625-3p expression and tumor budding, which is thought to represent epithelial-mesenchymal transition. Both studied miRNAs may be associated with a more aggressive phenotype and could be the potential prognostic and predictive biomarkers in CRC. Further investigation is needed to confirm miRNAs involvement in EMT, and their prognostic and predictive value.
miRNAs 在结直肠癌中经常失调，可能作为肿瘤抑制因子或癌基因发挥作用。它们参与控制增殖、侵袭和凋亡的关键信号通路，并可能作为预后和预测标志物。本研究旨在评估 miRNA-148a 和 miRNA-625-3p 在转移性结直肠癌中的作用。
54 例首次诊断为 CRC 的患者接受 FOLFOX ±贝伐单抗治疗，纳入本研究。肿瘤标本进行常规病理检查，包括评估肿瘤芽和 KRAS。通过 RT-PCR 进行 miRNA-148a 和 miRNA-625-3p 的表达分析。分析了这两种 miRNA 的表达与临床病理因素、治疗结果和生存之间的关系。
与正常结肠黏膜相比，肿瘤中两种 miRNA 均下调。与无芽肿瘤相比，有芽肿瘤中两种 miRNA 的表达明显降低（miRNA-148a 的中位数分别为 0.314 和 0.753，p=0.011，miRNA-625-3p 的中位数分别为 0.404 和 0.620，p=0.036）。与结肠肿瘤相比，直肠肿瘤中 miRNA-625-3p 的表达明显降低（中位数分别为 0.390 和 0.665，p=0.037）。高 miRNA-148a 表达的患者无进展生存期明显缩短（分别为 6 个月和 9 个月，p=0.033），但 miRNA-625-3p 的 PFS 和两种 miRNA 的总生存期无显著差异。
miRNA-148a 和 miRNA-625-3p 表达与肿瘤芽之间存在显著关系，这被认为代表上皮-间充质转化。这两种研究 miRNA 可能与更具侵袭性的表型相关，并且可能是 CRC 的潜在预后和预测生物标志物。需要进一步研究来确认 miRNAs 在 EMT 中的参与及其预后和预测价值。
