Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
Department of Breast Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
PLoS One. 2018 Jul 5;13(7):e0200315. doi: 10.1371/journal.pone.0200315. eCollection 2018.
The expression of fucosyltransferase 8, an enzyme responsible for core fucosylation encoded by FUT8, influences tumor biology and correlates with patient prognosis in several solid cancers. We hypothesized that p53 alteration modifies prognostic associations of FUT8 expression in colorectal cancer (CRC), since FUT8 has recently been identified as a direct transcriptional target of wild-type p53. Utilizing multiple datasets of microarray and RNA sequence of CRC, FUT8 mRNA was found to be highly expressed in wild-type p53 tumors (n = 382) compared to those of mutant p53 (n = 437). Prognostic values of FUT8 expression in conjunction with the p53 status for disease-free survival (DFS) were analyzed using two independent cohorts of stage II and III CRC after curative surgery, including the immunohistochemistry (IHC) cohort (n = 123) and the microarray cohort (n = 357). In both cohorts, neither FUT8 expression nor the p53 status was associated with DFS. Strikingly, positive expression of FUT8 protein was significantly associated with better DFS only in tumors with negative p53, while it had no prognostic impact in tumors with positive p53 in the IHC cohort. Although not statistically significant, a similar prognostic trend was observed in the microarray cohort when patients were stratified by the p53 status. Our results suggest that the prognostic values of FUT8 expression on DFS may be modified by the p53 status, and the expression of FUT8 protein can be a prognostic biomarker for patients with stage II and III CRC.
岩藻糖基转移酶 8 的表达,该酶负责由 FUT8 编码的核心岩藻糖基化,影响肿瘤生物学,并与几种实体瘤患者的预后相关。我们假设 p53 改变会改变结直肠癌(CRC)中 FUT8 表达的预后相关性,因为最近已经确定 FUT8 是野生型 p53 的直接转录靶标。利用 CRC 的多个微阵列和 RNA 序列数据集,与 p53 突变型(n = 437)相比,发现野生型 p53 肿瘤(n = 382)中 FUT8 mRNA 表达水平较高。使用两种独立的结直肠癌 II 期和 III 期根治性手术后的队列,包括免疫组化(IHC)队列(n = 123)和微阵列队列(n = 357),分析了 FUT8 表达与 p53 状态对无病生存期(DFS)的预后价值。在两个队列中,FUT8 表达和 p53 状态均与 DFS 无关。引人注目的是,仅在 p53 阴性的肿瘤中,FUT8 蛋白的阳性表达与更好的 DFS 显著相关,而在 p53 阳性的肿瘤中,它对 DFS 没有预后影响。尽管在统计学上没有意义,但在微阵列队列中,当根据 p53 状态对患者进行分层时,观察到了类似的预后趋势。我们的研究结果表明,FUT8 表达对 DFS 的预后价值可能受 p53 状态的影响,FUT8 蛋白的表达可以作为 II 期和 III 期结直肠癌患者的预后生物标志物。