Interferon-induced protein 16 expression in colorectal cancer and its correlation with proliferation and immune signature markers

Yunlian Zou; Jinping Zhang; Lichen Zhang; Xinmin Yan

doi:10.3892/ol.2021.12948

Interferon-induced protein 16 expression in colorectal cancer and its correlation with proliferation and immune signature markers

Oncol Lett. 2021 Sep;22(3):687. doi: 10.3892/ol.2021.12948. Epub 2021 Jul 28.

Authors

Yunlian Zou¹, Jinping Zhang², Lichen Zhang³, Xinmin Yan¹

Affiliations

¹ Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China.
² Institute of Medical Sciences, Yunnan Blood Disease Clinical Medical Center, The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650032, P.R. China.
³ Medical Faculty, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China.

Abstract

Interferon-induced protein 16 (IFI16) is important for innate immune recognition of foreign/damaged DNA. Abnormal IFI16 expression is closely related to the occurrence of multiple malignant tumours, but its expression pattern in colorectal cancer (CRC) remains unclear. The present study aimed to investigated IFI16 expression and association with cell proliferation in CRC tissues and adjacent normal tissues. A multiplex immunofluorescence panel of antibodies against IFI16, Ki-67 and phosphorylated (p)-ERK1/2 was applied to assess a tissue microarray (TMA). The TMA included 77 CRC samples and 74 normal adjacent tissue samples which were collected from The First People's Hospital of Yunnan Province (Kunming, China) (3 paracancerous tissues were lost because of repeated cutting). Immunohistochemistry was used to detect CD8⁺ tumour-infiltrating lymphocyte (TIL) abundance and programmed death-ligand 1 (PD-L1) expression in cancer tissues. The present study demonstrated that IFI16 localized to the nucleus of CRC cells. Although IFI16 was weakly expressed in normal mucosal epithelial cells, absent to strong expression was detectable in different patients with CRC. Typically, IFI16 was not co-localized with Ki-67 within CRC cells. The multiplex immunofluorescence data demonstrated that the proportion of IFI16^-/Ki-67⁺ cells from CRC tissues was 57.13%; however, that of IFI16⁺/Ki-67⁺ cells was 1.50%. The IFI16^-/Ki-67⁺ phenotype was significantly positively associated with the tumor-node-metastasis stage and was marginally significantly correlated with lymph node metastasis. p-ERK1/2 protein was primarily localized to the cytoplasm and cell membrane of CRC cells and sometimes to the nucleus. Although, IFI16 demonstrated a strong correlation with p-ERK1/2, IFI16 did not co-localize with p-ERK1/2 and the proportion of IFI16 and p-ERK1/2 double-negative CRC cells was 84.95%. IFI16 expression displayed no significant association with CD8⁺ TILs or PD-L1. However, a strong positive correlation between CD8⁺ TILs and PD-L1 was observed. High CD8⁺ TIL infiltration in CRC tissue was associated with lower lymph node metastasis and tumor-node-metastasis stage. In summary, the results of the present study provided a novel insight for the role of IFI16 in CRC occurrence via the regulation of cancer cell proliferation.

Keywords: CD8+ tumour-infiltrating lymphocyte; Ki-67; colorectal cancer; interferon-induced protein 16; phosphorylated-ERK1/2; programmed death-ligand 1.

Grants and funding

The present study was supported by the Health Bureau of Yunnan Province (grant nos. 2017NS226 and 2018NS0247); the Yunnan Digestive Endoscopy Clinical Medical Center Foundation for Health Commission of Yunnan Province (grant no. 2019LCZXKF-XH04); the Yunnan Blood Disease Clinical Medical Center Foundation for Health Commission of Yunnan Province (grant no. 2020LCZXKF-XY08); and in part by the Science and Technology Department of Yunnan Province (grant no. 2018DG010).