A case–control study of pre-operative levels of serum neutrophil gelatinase-associated lipocalin and other potential inflammatory markers in colorectal cancer

Abstract

BackgroundChronic inflammation is a key feature of colorectal cancer (CRC), meaning that inflammatory biomarkers may be useful for its diagnosis. In particular, high neutrophil gelatinase-associated lipocalin (NGAL) expression has been reported in CRC. Thus, we investigated whether serum NGAL and NGAL/MMP-9 could be potential biomarkers for the early detection of CRC. Concurrently, we studied other inflammatory biomarkers such as soluble tumor necrosis factor receptor 1 and 2 (sTNFR-1, sTNFR-2), and C reactive protein (CRP).MethodsThe AGARIC multicenter case–control study was performed in eastern France and included patients admitted for elective surgery either for a priori non-metastatic incident CRC (n = 224) or for benign causes (n = 252). Pre-operative serum levels of NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were measured.ResultsMedian values of serum NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were significantly higher in CRC patients than in controls. Receiver Operating Characteristic analysis provided relatively poor values of area under the curve, ranging from 0.65 to 0.58. Except for NGAL/MMP-9, all biological parameters were strongly correlated in CRC cases and, less strongly in controls. Multivariate odds ratio (OR) of CRC comparing the extreme tertiles of serum NGAL was 2.76 (95% confidence interval (CI): 1.59-4.78; p < 0.001),. Lower but significant multivariate associations were observed for sTNFR-1, and sTNFR-2: OR = 2.44 (95% CI : 1.34-4.45, p = 0.015) and 1.93 (95% : CI 1.12-3.31), respectively. No independent association was found between case–control status and NGAL/MMP-9. Among CRC cases, maximal tumor size was an independent determinant of serum NGAL (p = 0.028) but this association was reduced after adjustment for CRP (p = 0.11).ConclusionDespite a significant increase in serum NGAL and other inflammatory markers among CRC patients, our findings suggest that they may not be suitable biomarkers for the diagnosis and especially early detection of CRC.

Concomitant elevations of MMP‐9, NGAL, proMMP‐9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease

“…However, these relationships would need to be confirmed in a more extensive study of a larger cohort of healthy non‐smokers and smokers. In healthy adults, serum NGAL is correlated with age , but serum MMP‐9 may not be . In the present study, age‐corrected serum levels of MMP‐9 and proMMP‐9/NGAL were correlated with smoking status in patients with COPD but not in healthy smokers.…”

“…However, these relationships would need to be confirmed in a more extensive study of a larger cohort of healthy non-smokers and smokers. In healthy adults, serum NGAL is correlated with age [58,59], but serum MMP-9 may not be [60][61][62].…”

Circulating inflammatory markers and colorectal cancer risk: A prospective case‐cohort study in Japan

“…A case-control study reported higher levels of serum sTNFR2 in CRC cases than patients with benign disorders. 34 Prospective studies have had mixed results, with one study reporting a positive association with high levels and protection by aspirin/NSAID use that was restricted to individuals with high levels, 35 while two other studies were null. 36,37 BMI is a recognized risk factor for CRC.…”

Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy

“…Many transcription factors, including the estrogen and androgen receptors, regulate NGAL expression by both positive and negative mechanisms [67][68][69][70][71][72][73][74][75][76][77]. 11 NGAL is an important molecule in many different types of cancer including: breast [9,10,77], colorectal (CRC) [78,79], endometrial [80], esophageal [7,81], gastric cancer [6], liver [82][83][84], lung [85][86][87] ovarian [88], pancreatic [89,90], prostate [76,91], renal [8,92] and thyroid cancer [68]. In general, elevated NGAL expression has been associated with advanced cancer and poor prognosis.…”