Overexpression of neutrophil gelatinase-associated lipocalin and its receptor in colorectal carcinoma: Significant correlation with cell differentiation and tumour invasion

Abstract

Abstract. neutrophil gelatinase-associated lipocalin (ngAl), a member of the lipocalin family, is related to imflammation and tumour. Recently, a specific cell-surface receptor (24p3R/ NGALR) for lipocalin 24p3 was reported. However, the characteristics of ngAlr expression in colorectal carcinoma (crc) are not known. The objectives of this study were to investigate the expression of ngAl and ngAlr in crc specimens, and determine any relationship between the expression of these proteins and tumour progression. In the present study, crc specimens of 102 patients were obtained, and the expression of NGAL, NGALR, ferritin and Ki67 was analyzed in paraffin sections by immunohistochemistry. statistical analyses of the data collected were performed with SPSS software. We found that the cytoplasmic staining of ngAl, ngAlr and ferritin, as well as the nuclear staining of Ki67 were significantly upregulated in CRC tissues compared with normal colorectal tissues. Expression of NGAL was related to the deeper invasion of CRC (P=0.026), while NGALR was significantly associated with a deeper invasion (P=0.018) and a high degree of Tumor, Node and Metastasis stages (P=0.042) in CRC. The NGAL/NGALR co-expression was associated with poor cellular differentiation (P=0.004). Positive correlations between NGAL and NGALR (r=0.432, P<0.01), NGAL and ferritin (r=0.374, P<0.001), NGALR and Ki67 (r=0.228, P<0.05), NGAL/NGALR co-expression and ferritin (r=0.349, P<0.001), as well as NGAL/NGALR co-expression and Ki67 (r=0.205, P<0.05) were observed. However, the expression of NGAL or NGALR was not significantly associated with patient survival. These findings detected an elevated expression of NGAL and ngAlr resulting in poor cellular differentiation and a deeper invasion of CRC. Thus, NGALR may be a novel target for the treatment of crc.

The Diagnostic and Prognostic Significance of Serum Neutrophil Gelatinase-Associated Lipocalin Levels in Patients with Colorectal Cancer

“…Studies have been carried out to compare the NGAL expression levels in CRC with other tumor features such as cancer differentiation and localization of the tumor. As a result of these studies there were no significant correlations between NGAL expression level and tumor localization or cancer differentiation (25,39). Likewise, we did not find a correlation between serum NGAL levels and these features.…”

“…Nevertheless, there are inconsistent and even contradictory reports on the role of NGAL in the development and progression of cancer. Various studies were presented in the literature about genetic and immunohistochemical analyses on tissue samples to evaluate the diagnostic value of NGAL in CRC (19,21,25,(38)(39)(40). However, there is only one study available in current literature to evaluate the relationship between serum NGAL level and CRC.…”

Relation of Neutrophil Gelatinase-Associated Lipocalin Overexpression to the Resistance to Apoptosis of Tumor B Cells in Chronic Lymphocytic Leukemia

“…The present study is the first to have shown that the receptor for NGAL (SLC22A17; absent or weakly expressed in normal PBMCs) is strongly expressed by tumoral B cells from untreated CLL patients. Both NGAL and NGAL-R are upregulated in CLL, a situation similar to their expression pattern in various solid tumors where they are associated with clinical prognosis [56][57][58][59][60]. After treatment, total and surface NGAL-R levels fell to baseline levels in patients achieving clinical remission.…”

Neutrophil Gelatinase-Associated Lipocalin in Cancer

“…Lv et al investigated expression of NGAL using R&D Systems antibodies (Minneapolis, MN, USA) in specimens of 102 patients with colorectal cancer [44]. Expression of NGAL was significantly higher in colorectal cancer specimens compared with adjacent normal tissues (28.4% vs. 0%; p < 0.001).…”

“…Synopsis of available epidemiological studies linking neutrophil gelatinase-associated lipocalin (NGAL) with different forms of cancer Serum NGAL did not differ between cancer patients and controls ○ Urine NGAL 3.6-fold higher in cancer patients than in controls NGAL expression in 69% of cases ○ Higher NGAL expression in cancerous than in adjacent normal tissue ○ NGAL expression associated with depth of invasion, lymph node metastasis, venous involvement, and advanced stage Serum NGAL higher in high-risk patients, in those with >3 cancer nodules and with both lobes involvement Lv et al[44] Colorectal cancer Immunohistochemistry 102 -○ Higher NGAL expression in cancerous than in adjacent normal tissue ○ NGAL expression associated with cancer invasion…”