Department of General Surgery, Xiangya Hospital, Central South University, Changsha, P.R. China.
Department of Geriatric Surgery, Xiangya Hospital, Central South University, Changsha, P.R. China.
Aging (Albany NY). 2021 Aug 26;13(16):20609-20628. doi: 10.18632/aging.203451.
Stage III colorectal cancer (CRC) patients experience varying degrees of prognosis even if receiving standard therapeutic regimes. Intravascular emboli (IVE), a type of vascular invasion, impacts the clinical outcome in CRC. In this study, we confirmed the role of IVE in predicting the prognosis of stage III CRC patients and characterized the tumor microenvironment (TME) of CRC with IVE.
Data from 220 consecutive patients (cohort 1) with stage III CRC undergoing radical surgery was collected retrospectively between January 2009 to December 2014. According to the presence of IVE, which was confirmed by two independent pathologists, patients were classified into two groups. Univariate and multivariate Cox regression analyses were performed to evaluate the relation of IVE presence to patients' prognosis. The association between IVE and clinicopathological factors was also analyzed. Furthermore, differentially expressed genes (DEGs) and gene set enrichment analyses (GSEA) were performed to describe features of the TME based on microarray data consisting of 6 patients. Tumor tissues from a separate cohort of 73 patients with stage III CRC (cohort 2) collected between June 2014 and December 2015 were used to analyze tumor-infiltrating lymphocyte (TIL) by immunohistochemistry (IHC) staining.
IVE was observed in 126 (57.3%) patients and could serve as an unfavorable independent prognostic predictor (P < 0.001) as well as lymph node metastasis (P < 0.05) and tumor location (P < 0.05). Additionally, patients with IVE had a higher neutrophil percentage (P = 0.002) and lower lymphocyte percentage (P = 0.002) relative to those without IVE. CRC with IVE had a significantly different profile of DEGs compared to CRC without IVE, and GSEA showed chronic inflammatory and immunosuppressive TME may promote IVE development. In cohort 2, tumors with IVE had fewer CD3 TILs in the stromal region, as well as fewer CD8 TILs in both stromal and tumoral regions relative to those without IVE.
IVE, which was related closely to a chronic inflammatory and immunosuppressive TME, forecasted a worse prognosis of stage III CRC patients and may be taken into consideration when a therapeutic strategy is decided upon.
即使接受标准治疗方案，III 期结直肠癌（CRC）患者的预后也存在差异。血管内栓子（IVE）是血管侵犯的一种类型，影响 CRC 的临床结局。在这项研究中，我们证实了 IVE 在预测 III 期 CRC 患者预后中的作用，并对伴有 IVE 的 CRC 的肿瘤微环境（TME）进行了特征描述。
回顾性收集 2009 年 1 月至 2014 年 12 月期间接受根治性手术的 220 例连续 III 期 CRC 患者（队列 1）的数据。根据两位独立病理学家确认的 IVE 存在情况，将患者分为两组。进行单因素和多因素 Cox 回归分析，评估 IVE 存在与患者预后的关系。分析 IVE 与临床病理因素的关系。此外，基于由 6 例患者组成的微阵列数据进行差异表达基因（DEGs）和基因集富集分析（GSEA），以描述 TME 的特征。使用 2014 年 6 月至 2015 年 12 月期间收集的另一组 73 例 III 期 CRC 患者（队列 2）的肿瘤组织，通过免疫组织化学（IHC）染色分析肿瘤浸润淋巴细胞（TIL）。
126 例（57.3%）患者中观察到 IVE，可作为不良的独立预后预测因子（P<0.001）以及淋巴结转移（P<0.05）和肿瘤位置（P<0.05）。此外，与无 IVE 的患者相比，有 IVE 的患者中性粒细胞百分比更高（P=0.002），淋巴细胞百分比更低（P=0.002）。与无 IVE 的 CRC 相比，伴有 IVE 的 CRC 的 DEGs 谱明显不同，GSEA 显示慢性炎症和免疫抑制性 TME 可能促进 IVE 的发展。在队列 2 中，与无 IVE 的肿瘤相比，伴有 IVE 的肿瘤在基质区域中 CD3 TIL 较少，在基质和肿瘤区域中 CD8 TIL 也较少。
与慢性炎症和免疫抑制性 TME 密切相关的 IVE 预测了 III 期 CRC 患者的预后更差，在决定治疗策略时可能需要考虑这一点。
