Prognostic Impact of YKL-40 Immunohistochemical Expression in Patients with Colorectal Cancer

Abstract

This study aims to examine the clinicopathological and prognostic significance of the YKL-40 immunohistochemical expression of tumor and immune cells through human colorectal cancer (CRC) tissue. We performed immunohistochemistry for YKL-40 and investigated the clinicopathological and prognostic impact of the YKL-40 expression of tumor (T-YKL-40) and immune cells (I-YKL-40) in CRC. We also evaluated the correlation between YKL-40 and PD-L1 expression and the immunoscore. YKL-40 was expressed in 22.6% and 64.2% of T-YKL-40 and I-YKL-40, respectively, out of the 265 CRC tissues. The I-YKL-40 expression significantly correlated with well and moderately differentiated tumors. The PD-L1 expression in immune cells significantly correlated with the I-YKL-40 expression, but not T-YKL-40 expression (p = 0.020 and p = 0.846, respectively). The I-YKL-40 expression significantly correlated with a worse overall survival rate but not recurrence-free survival (p = 0.047 and p = 0.080, respectively). However, there was no significant correlation between the T-YKL-40 expression and survival. In CRCs with a high immunoscore, patients with I-YKL-40 expression demonstrated worse overall and recurrence-free survival than those without I-YKL-40 expression. Our results demonstrated that I-YKL-40 expression significantly correlated with tumor differentiation and PD-L1 expression in immune cells. I-YKL-40 expression can be useful for the prognostic stratification of CRC patients.

Do Elevated YKL-40 Levels Drive the Immunosuppressive Tumor Microenvironment in Colorectal Cancer? Assessment of the Association of the Expression of YKL-40, MMP-8, IL17A, and PD-L1 with Coexisting Type 2 Diabetes, Obesity, and Active Smoking

“…These findings seem to confirm crosstalk between PD-L1 and IL-17 pathways and support the literature data. In CRC, the expression of YKL-40 was reported to be significantly correlated with that of PD-L1 in immune cells; in tumor cells, the expression of YKL-40 did not correlate with the expression of PD-L1 [ 1 ]. In melanoma, YKL-40 was demonstrated to upregulate PD-L1 expression indirectly and directly by increasing the production of PD-L1 in monocytes stimulated by IFN-gamma.…”

“…According to literature data, both high tumor expression and elevated serum levels of YKL-40 are associated with poor outcomes in CRC patients, i.e., shorter overall survival and progression-free survival [ 65 ], which were not analyzed in our research. On the contrary, the association between YKL-40 expression and clinicopathological features such as tumor size, lymph node involvement, and histological grading has not yet been confirmed [ 1 ].…”

“…One of the most important factors determining prognosis in colorectal cancer (CRC) is the presence of metastases. Since metastatic CRC exhibits a poor prognosis, even with complete resection of the primary tumor, identification of new effective therapeutic targets to disrupt pathways involved in different stages of CRC metastasis is urgently needed [ 1 ]. Intercellular interactions in an abnormal tumor environment consisting of cancer and non-cancer cells, blood vessels, stroma, and the extracellular matrix might contribute to the high heterogeneity of CRC.…”

“…High levels of this glycoprotein have also been found in several tumors, such as colon, ovary, prostate, breast, lung, and kidney cancers, as well as melanoma. YKL-40 is closely related to chronic inflammation, cancer, and increased tissue remodeling [ 1 , 2 ]. Increased expression of YKL-40 was observed a the group of patients with obesity and type 2 diabetes, probably due to the involvement of YKL-40 in inflammatory processes [ 3 , 4 ].…”

“…It has been proven that YKL-40 promotes tumor progression, mainly through the regulation of extracellular matrix remodeling and inflammation. Many studies indicate that its serum level is associated with adverse clinical outcomes of patients with CRC and other solid tumors and might serve as a marker of poor prognosis [ 1 , 5 ].…”