Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan.
Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Int J Colorectal Dis. 2019 Oct;34(10):1731-1739. doi: 10.1007/s00384-019-03379-y. Epub 2019 Sep 2.
Angiotensin signaling is suggested to be involved in tumorigenesis, tumor proliferation, and metastases. In colorectal cancer (CRC), it was demonstrated that angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may reduce the risk of CRC; however, their impact on tumor recurrence remains unknown. Therefore, in this study, we evaluated the impact of ACEIs/ARBs on tumor recurrence in CRC patients.
We retrospectively investigated the clinicopathological data of 461 stage I-III CRC patients. We divided the patients into those who took an ACEI and/or ARB (the ACEI/ARB+ group) and those who did not (the ACEI/ARB- group), and we compared the two groups' recurrence-free survival (RFS) using a Kaplan-Meier curve analysis and log rank test. We also examined the impact of AGTR1 expression on tumor recurrence, using two public CRC datasets.
The Kaplan-Meier curves showed a trend toward improved RFS in the ACEI/ARB+ group versus the ACEI/ARB- group (p = 0.063). Subgroup analyses demonstrated that the RFS was significantly better in the ACEI/ARB+ group versus the ACEI/ARB- group in the patients with left-sided CRC (p = 0.030) and those with stage I CRC (p = 0.009). Consistent with these findings, the AGTR1 expression was higher in the left-sided versus right-sided colon (p = 0.048). High AGTR1 expression levels were associated with poor RFS in the GSE39582 dataset's stage I-III CRC patients (p < 0.001), and this finding was also validated in the GSE17536 dataset (p = 0.023).
ACEI/ARB treatment may reduce tumor recurrence in left-sided CRC and early-stage CRC.
血管紧张素信号被认为参与肿瘤发生、肿瘤增殖和转移。在结直肠癌(CRC)中,已经证明血管紧张素转换酶抑制剂(ACEI)和血管紧张素 II 受体阻滞剂(ARB)可能降低 CRC 的风险;然而,它们对肿瘤复发的影响尚不清楚。因此,在这项研究中,我们评估了 ACEI/ARB 对 CRC 患者肿瘤复发的影响。
我们回顾性调查了 461 例 I-III 期 CRC 患者的临床病理数据。我们将患者分为服用 ACEI 和/或 ARB(ACEI/ARB+组)和未服用 ACEI/ARB(ACEI/ARB-组)的患者,并使用 Kaplan-Meier 曲线分析和对数秩检验比较两组的无复发生存率(RFS)。我们还使用两个公共 CRC 数据集检查了 AGTR1 表达对肿瘤复发的影响。
Kaplan-Meier 曲线显示 ACEI/ARB+组的 RFS 趋势优于 ACEI/ARB-组(p=0.063)。亚组分析表明,在左半侧 CRC 患者(p=0.030)和 I 期 CRC 患者(p=0.009)中,ACEI/ARB+组的 RFS 明显优于 ACEI/ARB-组。与这些发现一致的是,AGTR1 表达在左半结肠中高于右半结肠(p=0.048)。在 GSE39582 数据集的 I-III 期 CRC 患者中,高 AGTR1 表达水平与较差的 RFS 相关(p<0.001),这一发现也在 GSE17536 数据集得到验证(p=0.023)。
ACEI/ARB 治疗可能降低左半侧 CRC 和早期 CRC 的肿瘤复发率。