Liang Wenfeng, Jie Haiqing, Xie Hao, Zhou Yebohao, Li Wenxin, Huang Liang, Liang Zhenxing, Liu Huashan, Zheng Xiaobin, Zeng Ziwei, Kang Liang
Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China.
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China.
Clin Transl Immunology. 2024 Feb 29;13(3):e1495. doi: 10.1002/cti2.1495. eCollection 2024.
Emerging evidence has demonstrated that tumour budding (TB) is negatively associated with T-lymphocyte infiltration in CRC. Despite extensive research, the molecular characteristics of immunologically 'hot' TB remain poorly understood.
We quantified the number of TB by haematoxylin-eosin (H&E) sections and the densities of CD3 and CD8 T-lymphocytes by immunohistochemistry in a CRC cohort of 351 cases who underwent curative resection. We analysed the differential expression and T-lymphocyte infiltration score of 37 human epithelial keratins in CRC using RNA sequencing from the TCGA dataset. In 278 TB-positive cases, KRT17 expression was evaluated in tumour centre (TC) and TB with a staining score. Patient demographic, clinicopathological features and survival rates were analysed.
In a CRC cohort of 351 cases, low-grade TB was associated with high CD3 and CD8 T-cell densities in the invasive margin (IM) but not in the TC. Of 37 human epithelial keratins, only KRT17 expression in TB had an apparent association with TB-grade and T-lymphocyte infiltration. In 278 TB-positive cases, high KRT17 expression in TB (KRT17TB) was negatively associated with low-grade TB and positively associated with high CD3 and CD8 T-cell densities in IM. High KRT17TB predicted early tumour grade, absence of lymph node metastasis and absence of tumour deposits. Additionally, patients with high KRT17TB had good overall survival and disease-free survival. Notably, low KRT17TB can specifically identify those patients with a poor prognosis among colorectal cancer patients with low TB and high T-lymphocyte infiltration.
KRT17 can be employed as a new indicator for distinguishing different immunological TBs.
新出现的证据表明，肿瘤芽生（TB）与结直肠癌中的T淋巴细胞浸润呈负相关。尽管进行了广泛研究，但免疫“热”TB的分子特征仍知之甚少。
我们通过苏木精-伊红（H&E）切片对351例行根治性切除的结直肠癌患者队列中的TB数量进行定量，并通过免疫组化对CD3和CD8 T淋巴细胞密度进行定量。我们使用来自TCGA数据集的RNA测序分析了37种人类上皮角蛋白在结直肠癌中的差异表达和T淋巴细胞浸润评分。在278例TB阳性病例中，通过染色评分评估肿瘤中心（TC）和TB中的KRT17表达。分析患者的人口统计学、临床病理特征和生存率。
在351例结直肠癌患者队列中，低级别TB与浸润边缘（IM）而非TC中的高CD3和CD8 T细胞密度相关。在37种人类上皮角蛋白中，只有TB中的KRT17表达与TB分级和T淋巴细胞浸润有明显关联。在278例TB阳性病例中，TB中高KRT17表达（KRT17TB）与低级别TB呈负相关，与IM中高CD3和CD8 T细胞密度呈正相关。高KRT17TB预测早期肿瘤分级、无淋巴结转移和无肿瘤沉积。此外，KRT17TB高的患者总生存期和无病生存期良好。值得注意的是，低KRT17TB可以特异性地识别出TB低且T淋巴细胞浸润高的结直肠癌患者中预后较差的患者。
KRT17可作为区分不同免疫性TB的新指标。
