Galectin-3 and cyclin D1 expression in non-small cell lung cancer

Abstract

IntroductionLung cancer is a major cause of mortality and morbidity worldwide. Galectin-3 is multifunctional protein, which is involved in regulation of cell growth, cell adhesion, cell proliferation, angiogenesis and apoptosis. Cyclin D1 together with other cyclin plays an important role in cell cycle control. Cyclin D1 regulates the G1-to-S phase transition. The aim of this study was the evaluation of correlations between clinicopathological findings and cyclin D1 and galectin-3 expression in non-small cell lung cancer (NSCLC). We wanted also to analyze the prognostic value of cyclin D1 and galectin-3 expression. Moreover we tried to evaluate the correlations between galectin-3 and cyclin D1 expression in tumor tissue.Materials and methodsWe used the immunochemistry method to investigate the expression of galectin-3 and cyclin D1 in the paraffin-embedded tumor tissue of 47 patients (32 men and 15 women; mean age 59.34 ± 8.90). years. We used monoclonal antibodies to cyclin D1 (NCL-L-cyclin D1-GM clone P2D11F11 NOVO CASTRA) and to galectin-3 (mouse monoclonal antibody NCL-GAL3 NOVO CASTRA).ResultsGalectin-3 expression was positive in 18 cases (38.29%) and cyclin D1 in 39 (82.97%). We showed only weak trend, that galectin-3 expression was lower in patients without lymph node involvement (p = 0.07) and cyclin D1 expression was higher in this group (p = 0.080). We didn't reveal differences in cyclin D1 and galectin-3 expression in SCC and adenocarcinoma patients. We didn't demonstrated also differences in galectin-3 and cyclin D1 expression depending on disease stage. Moreover we analyzed the prognostic value of cyclin D1 expression and galectin-3 in all examinated patients and separately in SCC and in adenocarcinoma and in all stages, but we didn't find any statistical differences. We demonstrated that in galectin-3 positive tumors cyclin D1 expression was higher (96.55% vs 61.11%, Chi2 Yatesa 7.53, p = 0.0061) and we revealed negative correlation between cyclin D1 and galectin-3 expression (R Spearman -0.458, p = 0.0011). In squamous cell lung cancer we didn't observed correlations between these both examinated markers (R = -0.158, p = 0.460), and in adenocarcinoma the negative correlation was very strong (R = -0.829 p = 0.000132).ConclusionsWe didn't reveal any important correlations between clinicopathological findings and galectin-3 and cyclin D1 expression and in non small cell lung cancer. We didn't observed also prognostic value of cyclin D1 or galectin-3 expression. But we showed higher cyclin D1 expression in galectin-3 negative tumor tissues. We revealed also differences in correlations between galectin-3 and cyclin D1 expression in two main histopathological types of NSCLC.

Role of cell cycle regulators in lung carcinogenesis

“…Elevated levels of cyclin A are observed in primary NSCLC, in lymph node metastasis and in some bronchial precursor lesions as compared to normal bronchial epithelium. [82][83][84][85] Several studies have reported that overexpression of cyclin A is consistently associated with an unfavourable outcome in patients with NSCLC. [83][84][85] Moreover, elevated levels of the licensing factors hCdt1 and hCdc6 that are key elements for DNA replication, are observed in NSCLC and correlate to increased tumor growth and aneuploidy in p53-defective tumors.…”

Prognostic Value of Expression of Cyclin E in Gastrointestinal Cancer

“…Overexpression of cyclins and CDKs and loss of expression of CKIs (CDK inhibitors) are frequently reported in human neoplasia. The overexpression of cyclin E is common in various types of cancer, including breast cancer, 3,4 nonsmall cell lung cancer (NSCLC), 5,6 colon cancer, 7 bladder cancer, 8 and ovarian cancer. 9 Cancers of the digestive system are common worldwide, while the pattern and incidence vary widely between different parts of the world.…”

Mitomycin C and doxorubicin elicit conflicting signals by causing accumulation of cyclin E prior to p21WAF1/CIP1 elevation in human hepatocellular carcinoma cells

“…Cyclins, and the catalytic partners thereof, the cyclin-dependent kinases (CDKs), feature strongly in such work. Aberrant expression of such proteins, particularly cyclin D 1 and cyclin E, that control the G 1 phase of the cell cycle, is found in a variety of human cancers (1,2). Overexpression of cyclin D1 and cyclin E accelerates the G 1 -S-phase transition (3), causes chromosomal instability (4), and alters the sensitivity of cells to anticancer agents (5).…”