High KRT17 expression in tumour budding indicates immunologically ‘hot’ tumour budding and predicts good survival in patients with colorectal cancer

Abstract

Objectives

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.

Methods

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.

Results

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.

Conclusions

KRT17 can be employed as a new indicator for distinguishing different immunological TBs.