Clinical significance of Fusobacterium nucleatum, epithelial-mesenchymal transition, and cancer stem cell markers in stage III/IV colorectal cancer patients.
Clinical significance of Fusobacterium nucleatum, epithelial-mesenchymal transition, and cancer stem cell markers in stage III/IV colorectal cancer patients.
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III / IV 期结直肠癌患者中具核梭杆菌、上皮-间质转化和癌症干细胞标志物的临床意义。
DOI：
10.2147/ott.s145949
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发表时间：
2017
影响因子：
4
通讯作者：
Sun Z
中科院分区：
文献类型：
--
作者：
Yan X;Liu L;Li H;Qin H;Sun Z
结直肠癌（CRC）是一种常见的消化道恶性肿瘤，新兴的研究将其发生和发展与肠道微生物群的变化密切相关。具核梭杆菌（Fn）最近已被确定为大肠癌的致病菌;然而，其对患者的预后意义研究甚少，对晚期患者的预后意义较小。因此，在本研究中，我们在280例III/IV期结直肠癌患者的回顾性队列中分析了其水平和预后意义。我们发现肿瘤组织中Fn水平异常升高，并与肿瘤浸润、淋巴结转移和远处转移有关。我们还将其确定为癌症特异性生存期（CSS）和无病生存期（DFS）的独立不良预后因素。以下亚组分析表明，Fn水平可以分层的CSS和DFS在IIIB/C和IV期患者，但在IIIA期患者失败。此外，低Fn水平的III/IV期患者在DFS方面比高Fn水平的患者从辅助化疗中获益更多。最后，我们分析了上皮间质转化（EMT）标志物（E-cadherin和N-cadherin）和癌症干细胞（CSC）标志物（Nanog，Oct-4和Sox-2）在结直肠癌组织中的表达及其临床意义。结果表明，N-cadherin，Nanog，Oct-4和Sox-2是这些患者的不良预后因素，而E-cadherin则相反。更重要的是，E-cadherin、N-cadherin和Nanog的表达与肿瘤组织中的Fn水平显著相关，表明Fn在CRC进展期间可能参与EMT-CSC串扰。总之，这些发现表明Fn是III/IV期患者临床管理的一种新的预测生物标志物，靶向Fn可能是预防CRC转移和化疗耐药的有效辅助方法。
Colorectal cancer (CRC) is a common digestive malignancy and emerging studies have closely linked its initiation and development with gut microbiota changes. Fusobacterium nucleatum (Fn) has been recently identified as a pathogenic bacteria for CRC; however, its prognostic significance for patients is poorly investigated and is less for patients within late stage. Therefore, in this study, we made efforts to analyze its level and prognostic significance in a retrospective cohort of 280 stage III/IV CRC patients. We found that the Fn level was abnormally high in tumor tissues and correlated with tumor invasion, lymph node metastasis status, and distant metastasis. We also identified it as an independent adverse prognostic factor for cancer-specific survival (CSS) and disease-free survival (DFS). The following subgroup analysis indicated that Fn level could stratify CSS and DFS in stage IIIB/C and IV patients but failed in stage IIIA patients. In addition, stage III/IV patients with low Fn level were found to benefit more from adjuvant chemotherapy than those with high Fn level, in terms of DFS. Finally, we analyzed the expression and clinical significance of epithelial-to-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin) and cancer stem cell (CSC) markers (Nanog, Oct-4, and Sox-2) in CRC tissues. The results indicated that N-cadherin, Nanog, Oct-4, and Sox-2 were adverse prognostic factors in these patients, while the opposite was true for E-cadherin. More importantly, expression of E-cadherin, N-cadherin, and Nanog was significantly correlated with Fn level in tumor tissues, suggesting the potential involvement of Fn in EMT-CSC cross talk during CRC progression. Taken together, these findings indicate that Fn is a novel predictive biomarker for clinical management in stage III/IV patients, and targeting Fn may be an effective adjuvant approach for preventing CRC metastasis and chemotherapy resistance.