Nuclear Localization of Chitinase 3-like 1 Is a Novel Biomarker for Detecting the Early Stage of Inflammation-associated Dysplasia in the Oral Cavity

Although the oral cavity is a site that can be seen directly, early detection of oral cancer remains challenging, with a cumulative 5-year survival rate of approximately 55% across all stages of the cancer, leading to poor treatment outcomes. Chitinase 3-like 1 (CHI3L1/YKL-40), is a chitinase-like protein that binds to chitin (a polymer of N-acetylglucosamine) despite lacking enzymatic activity. CHI3L1 is strongly expressed in colonic epithelial cells (CECs) under inflammatory conditions. Although CHI3L1 has been implicated in the carcinogenic transformation of CECs, the precise underlying mechanisms remain unclear. CHI3L1 expression in oral epithelial cells was evaluated by immunofluorescence staining and quantitative-PCR. Immunostaining for CHI3L1 was conducted on paraffin-embedded tissue specimens, including oral squamous cell carcinoma (n=4) and carcinoma in situ (CIS; n=6) as malignant cases, and oral leukoplakia (n=29) as a precancerous condition. The nuclear-to-cytoplasmic ratio of the immunofluorescence signal was analyzed in each group. CHI3L1 was found to be strongly expressed in the nucleus among patients with oral leukoplakia developing dysplasia (85.7%) or CIS (100%), whereas CHI3L1 exhibited weak and diffuse cytoplasmic expression in advanced cancer patients. These results suggest that CHI3L1 may temporarily translocate into the nucleus under chronic inflammatory conditions, leading to a transition to a precancerous stage. Nuclear translocation of CHI3L1 from cytoplasm seems to be a reliable biomarker for detecting the precancerous stage of oral epithelium under chronic inflammatory conditions.