Aksoy Fuat, Ak-Aksoy Secil, Karamustafaoglu Ahmet, Tekin Cagla, Ercelik Melis, Tunca Berrin, Duman Busra Oncel, Isik Ozgen, Ugras Nesrin, Kaya Ekrem
Department of General Surgery, Faculty of Medicine, Bursa Uludag University, Bursa 16059, Turkey.
Department of Medical Microbiology, Faculty of Medicine, Bursa Uludag University, Bursa 16059, Turkey.
Life (Basel). 2025 May 29;15(6):877. doi: 10.3390/life15060877.
Surgery is one of the most effective treatment methods for liver metastases developing from primary colorectal cancer (CRC). Despite the widespread application of surgical approaches, recurrence rates remain substantial. Although chemotherapy is frequently employed, the supporting evidence for its efficacy in this context remains inconclusive. In the present study, we aimed to identify potential predictors of post-metastasectomy recurrence by analyzing clinical, pathological, and molecular features of both primary colorectal tumors and their corresponding hepatic metastases. Specifically, we evaluated the expression of epithelial-mesenchymal transition (EMT) markers, cancer stem cell (CSC) markers, and selected oncogenic mRNAs (RAS, mTOR, and CMYC) in tissue samples from 84 patients. RAS and CMYC are well-known proto-oncogenes involved in cell proliferation and survival, while mTOR functions as a central regulator of cell growth and metabolism. Following liver metastasectomy, intra-hepatic recurrence was observed in 40.5% of the cases. Among the molecular markers analyzed, the EMT transcription factor SNAIL-which plays a critical role in cancer cell invasion and metastasis-and mTOR exhibited significantly elevated expression in metastatic lesions from patients who experienced recurrence. While SNAIL expression did not show a clear association with the time to recurrence, increased mTOR expression in metastatic liver tissue was significantly associated with both shorter recurrence-free survival and diminished overall survival ( < 0.001). Results showed that expression levels could be a clinically relevant predictive indicator of remnant liver recurrence. In patients with liver metastases, the use of inhibitors may be considered after hepatic metastasectomy.
手术是治疗原发性结直肠癌(CRC)肝转移最有效的方法之一。尽管手术方法已广泛应用,但复发率仍然很高。虽然化疗经常被使用,但其在这种情况下疗效的支持证据仍然不确定。在本研究中,我们旨在通过分析原发性结直肠癌肿瘤及其相应肝转移灶的临床、病理和分子特征,确定转移灶切除术后复发的潜在预测因素。具体而言,我们评估了84例患者组织样本中上皮-间质转化(EMT)标志物、癌症干细胞(CSC)标志物和选定的致癌mRNA(RAS、mTOR和CMYC)的表达。RAS和CMYC是参与细胞增殖和存活的著名原癌基因,而mTOR是细胞生长和代谢的核心调节因子。肝转移灶切除术后,40.5%的病例出现肝内复发。在分析的分子标志物中,在癌细胞侵袭和转移中起关键作用的EMT转录因子SNAIL和mTOR在复发患者的转移灶中表达显著升高。虽然SNAIL表达与复发时间没有明显关联,但转移肝组织中mTOR表达增加与无复发生存期缩短和总生存期降低均显著相关(P<0.001)。结果表明, 表达水平可能是残余肝复发的临床相关预测指标。在肝转移患者中,肝转移灶切除术后可考虑使用 抑制剂。