Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Cancer Rep (Hoboken). 2023 Dec;6(12):e1899. doi: 10.1002/cnr2.1899. Epub 2023 Sep 12.
Colorectal cancer ranks second in terms of cancer associated deaths worldwide, whereas miRNA play a pivotal role in the etiology of cancer and its metastases.
Studying the expression and cellular function of miR-18a in metastatic colorectal cancer and association to progression-free survival.
Colorectal liver metastases (N = 123) and primary colorectal cancer (N = 27) where analyzed by RT-PCR and correlated with clinical follow up data. Invasion and migration assays were performed with the liver metastatic cell line LIM2099 after miR-18a knockdown. Cell viability under FOLFOX treatment and knockdown was measured. We found that the expression of miR-18a was increased 4.38-fold in liver metastases and 3.86-fold in colorectal tumor tissue compared to healthy liver tissue and colorectal mucosa, respectively (p ≤ .001). Patients with a high miR-18a expression in liver metastases had a progression-free survival (PFS) of 13.6 months versus 8.9 months in patients with low expression (N = 123; p = .024). In vitro migration of LIM2099 cells was reduced after miR-18a knockdown and cell viability was significantly increased after miR-18a knockdown and treatment with folinic acid or oxaliplatin. Subgroup analysis of PFS revealed significant benefits for patients with high miR-18a expression receiving 5-FU, folinic acid or oxaliplatin.
High expression of miR-18a in colorectal liver metastases might have a protective effect after resection of metastases and FOLFOX treatment regarding PFS.
结直肠癌在全球癌症相关死亡中排名第二，而 miRNA 在癌症及其转移的发病机制中起着关键作用。
研究转移性结直肠癌中 miR-18a 的表达和细胞功能及其与无进展生存期的关系。
通过 RT-PCR 分析结直肠肝转移（N=123）和原发性结直肠癌（N=27），并与临床随访资料相关联。在 miR-18a 敲低后，用肝转移性细胞系 LIM2099 进行侵袭和迁移实验。在 FOLFOX 治疗和敲低下测量细胞活力。我们发现，与健康肝组织和结直肠黏膜相比，miR-18a 在肝转移和结直肠肿瘤组织中的表达分别增加了 4.38 倍和 3.86 倍（p≤.001）。肝转移中 miR-18a 高表达的患者无进展生存期（PFS）为 13.6 个月，而低表达的患者为 8.9 个月（N=123；p=0.024）。miR-18a 敲低后 LIM2099 细胞的迁移减少，miR-18a 敲低后细胞活力显著增加，在用亚叶酸或奥沙利铂治疗后。PFS 的亚组分析显示，高 miR-18a 表达的患者接受 5-FU、亚叶酸或奥沙利铂治疗的获益显著。
结直肠肝转移中 miR-18a 的高表达可能在转移切除和 FOLFOX 治疗后对 PFS 有保护作用。
