Irisin Association with Ki-67, MCM3 and MT-I/II in Squamous Cell Carcinomas of the Larynx

Abstract

Background: Current studies indicate irisin role in carcinogenesis. The aim of the study was to investigate the expression of irisin in LSCCs and to determine its association with clinicopathological factors, as well as recognized markers of proliferation, i.e., Ki-67 and MCM3,5,7 and MT-I/II proteins. Material and methods: The research material consisted of 140 cases of LSCCs, 57 cases of laryngeal papillomas (BLs) and 14 controls (benign hypertrophic changes). Tissue microarrays were used to perform IHC. Western blot and immunofluorescence were performed in laryngeal cancer cell lines and normal keratinocytes. Results: Irisin expression levels were significantly increased in LSCC compared to BLs (p < 0.0001) and controls (p = 0.001). We noted a positive moderate and weak correlation between irisin and Ki-67, MCM3 and MT-I/II. We observed an elevated level of irisin expression with increasing tumor size (T1–2 vs. T3–4; p = 0.0348). The levels of irisin were higher in N0 than in N1 and N2–3 (p = 0.0031 and p = 0.0457, respectively). Our in vitro study revealed a higher level of irisin in Larynx Epidermoid Carcinoma 2 (HEp-2) cells compared to the control Normal Human Keratinocyte (HaCat) cell line. Conclusions: Increased irisin expression levels in LSCC and its correlation with clinicopathological and proliferation factors may indicate the potential role of irisin as a biomarker in the diagnostic process of LSCC.

Expression of Irisin/FNDC5 in Breast Cancer

“…This may indicate an inhibitory role of irisin in the EMT process of BC cells. Studies by Nowinska et al [ 20 ], Pinkowska et al [ 19 ], and Zhang et al [ 27 ] support our hypothesis. Further studies are warranted to elucidate the mechanism of how irisin affects EMT inhibition and metastasis formation.…”

“…In our previous study [ 20 ], we observed a decrease in irisin levels in non-small cell lung carcinoma (NSCLC) cells from patients with lymph node metastases (N1) compared to those without metastases. We also reported a similar observation in laryngeal squamous cell carcinoma (LSCC) [ 19 ].…”

“…Panagiotou et al [ 26 ] examined serum irisin levels in patients with benign and malignant breast cancer lesions and also observed a weak positive correlation with Ki-67 antigen expression. Pinkowska et al [ 19 ] found a moderate positive correlation of irisin with Ki-67 expression in LSCC. Irisin in LSCC was also correlated with other proliferation markers, i.e., minichromosome maintenance protein 3 (MCM3) and metallothioneins I/II (MT-I/II) [ 19 ].…”

“…Pinkowska et al [ 19 ] found a moderate positive correlation of irisin with Ki-67 expression in LSCC. Irisin in LSCC was also correlated with other proliferation markers, i.e., minichromosome maintenance protein 3 (MCM3) and metallothioneins I/II (MT-I/II) [ 19 ]. However, Wozniak et al [ 36 ] reported a weak correlation between irisin and Ki-67, MCM3 protein, and urine diphosphate-galactose ceramide galactosyltransferase (UGT8) in colorectal cancer (CRC).…”

“…Further studies have shown that increased irisin levels are found in malignant lesions, such as lung cancer, gastrointestinal cancer, ovarian cancer, clear cell renal cell carcinoma, laryngeal cancer, and osteosarcoma [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. In our previous paper, we observed an association of FNDC5/irisin expression with the histological malignancy grade, tumor size, and lymph node metastases in non-small cell lung carcinoma (NSCLC) [ 20 ].…”