Huang Jing Li, Oshi Masanori, Endo Itaru, Takabe Kazuaki
Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center Buffalo, New York 14263, USA.
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine Yokohama 236-0004, Japan.
Am J Cancer Res. 2021 Oct 15;11(10):5141-5154. eCollection 2021.
Colon cancer stem cells (CSC) identified by cell surface markers CD133, CD24, and CD44, have been shown to be involved with tumor formation, chemotherapy resistance, and the progression of metastatic disease. Using an translational approach, we hypothesize that a combination of these CSC markers has prognostic value in a large cohort of patients with colorectal cancer. Clinicopathologic and RNA expression data from a total of 594 colorectal cancer (CRC) patients from TCGA were analyzed. The expression of CD133, CD24, and CD44 was individually defined as "high" or "low" based on the median expression. Disease specific survival (DSS) and overall survival (OS) were not associated with tumors that are CD133-high or CD44-high alone. Patients with CD24-high tumors have significantly better DSS (P<0.001) and OS (P = 0.043). CD24-high, CD44-high and CD133-high tumors were associated with significantly greater EGFR, KRAS and Ki67 expression (all P<0.001). CD133, CD24 and CD44-high tumors were independently enriched for conventional stemness-related signaling pathways such as Wnt/β-catenin and Hedgehog signaling pathways. There was no survival difference linked to CD133-high/CD44-low patients, but CD44-high/CD24-low patients have worse DSS (P = 0.005) compared with CD44-low/CD24-high patients. CD133-high/CD24-low tumors show significant negative enrichment of MYC targets, E2F targets, G2M checkpoint and mitotic spindle gene sets, suggesting less cell proliferation in these tumors. Patients with CD133-high/CD24-low tumors have worse DSS (P = 0.004) and OS (P = 0.044), and are more likely to have early and late recurrences. In conclusion, we demonstrated that CD133-high/CD24-low tumors may predict colorectal cancer prognosis.
通过细胞表面标志物CD133、CD24和CD44鉴定出的结肠癌干细胞（CSC），已被证明与肿瘤形成、化疗耐药性及转移性疾病进展有关。采用转化医学方法，我们假设这些CSC标志物的组合在一大群结直肠癌患者中具有预后价值。分析了来自TCGA的总共594例结直肠癌（CRC）患者的临床病理和RNA表达数据。基于中位表达，将CD133、CD24和CD44的表达分别定义为“高”或“低”。疾病特异性生存（DSS）和总生存（OS）与单独的CD133高或CD44高的肿瘤无关。CD24高的肿瘤患者具有显著更好的DSS（P<0.001）和OS（P = 0.043）。CD24高、CD44高和CD133高的肿瘤与显著更高的EGFR、KRAS和Ki67表达相关（所有P<0.001）。CD133、CD24和CD44高的肿瘤独立地富集了诸如Wnt/β-连环蛋白和Hedgehog信号通路等传统的干性相关信号通路。CD133高/CD44低的患者没有生存差异，但与CD44低/CD24高的患者相比，CD44高/CD2,4低的患者DSS更差（P = 0.005）。CD133高/CD24低的肿瘤显示MYC靶点、E2F靶点、G2M检查点和有丝分裂纺锤体基因集显著负富集，表明这些肿瘤中的细胞增殖较少。CD133高/CD24低的肿瘤患者DSS更差（P = 0.004）和OS更差（P = 0.044），并且更有可能发生早期和晚期复发。总之，我们证明CD133高/CD24低的肿瘤可能预测结直肠癌的预后。
