Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer

Abstract

BACKGROUND: Macrophage inhibitory cytokine-1(MIC-1) is a potential modulator of systemic inflammation and nutritional depletion, both of which are adverse prognostic factors in oesophago-gastric cancer (OGC). METHODS: Plasma MIC-1, systemic inflammation (defined as plasma C-reactive protein (CRP) of X10 mg l -1 or modified Glasgow prognostic score (mGPS) of X1), and nutritional status were assessed in newly diagnosed OGC patients (n ¼ 293). Healthy volunteers (n ¼ 35) served as controls. RESULTS: MIC-1 was elevated in patients (median ¼ 1371 pg ml -1 ; range 141 -39 053) when compared with controls (median ¼ 377 pg ml -1 ; range 141 -3786; Po0.001). Patients with gastric tumours (median ¼ 1592 pg ml -1 ; range 141 -12 643) showed higher MIC-1 concentrations than patients with junctional (median ¼ 1337 pg ml -1 ; range 383 -39 053) and oesophageal tumours (median ¼ 1180 pg ml -1 ; range 258 -31 184; P ¼ 0.015). Patients showed a median weight loss of 6.4% (range 0.0 -33.4%), and 42% of patients had an mGPS of X1 or plasma CRP of X10 mg l -1 (median ¼ 9 mg l -1 ; range 1 -200). MIC-1 correlated positively with disease stage (r 2 ¼ 0.217; Po0.001), age (r 2 ¼ 0.332; Po0.001), CRP (r 2 ¼ 0.314; Po0.001), and mGPS (r 2 ¼ 0.336; Po0.001), and negatively with Karnofsky Performance Score (r 2 ¼ À0.269; Po0.001). However, although MIC-1 correlated weakly with dietary intake (r 2 ¼ 0.157; P ¼ 0.031), it did not correlate with weight loss, BMI, or anthropometry. Patients with MIC-1 levels in the upper quartile showed reduced survival (median ¼ 204 days; 95% CI 157 -251) when compared with patients with MIC-1 levels in the lower three quartiles (median ¼ 316 days; 95% CI 259 -373; P ¼ 0.036), but MIC-1 was not an independent prognostic indicator. CONCLUSIONS: There is no independent link between plasma MIC-1 levels and depleted nutritional status or survival in OGC.

Weight Loss Correlates with Macrophage Inhibitory Cytokine-1 Expression and Might Influence Outcome in Patients with Advanced Esophageal Squamous Cell Carcinoma

“…In our study, elevated serum MIC-1 concentration was associated with shorter survival on univariate but not on multivariate analysis, which was consistent with the results of the study by Skipworth et al (Skipworth et al, 2010). Such difference may be explained by the different definitions of MIC-1 elevation.…”

“…Our study did demonstrate that MIC-1 concentration was closely related to weight loss before chemotherapy, which indicated that MIC-1 may cause weight loss by decreasing appetite in ESCC patients. Some studies had also indicated that serum MIC-1 was closely associated with energy intake and expenditure and systemic inflammation (Skipworth RJ et al, 2010;Tsai VW et al, 2013). Our study concerning those fields is ongoing.…”

GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways

“…The serum GDF15 concentration has been reported to be closely associated with the depth of invasion, lymph node metastasis, and overall survival of ESCC patients. 42,47 However, a detailed statistical analysis of the immunohistochemical expression of GDF15 in the ESCC tissues and the clinicopathological factors of the patients had not been described before the present study. We found that the immunoreactivity of GDF15 in the microenvironment of ESCCs was correlated with many clinicopathological factors: the depth of invasion, lymphatic vessel invasion, blood vessel invasion, lymph node metastasis, clinical stages, overall survival, and disease-free survival.…”

Circulating Levels of GDF15, MMP7 and miR-200c as a Poor Prognostic Signature in Gastric Cancer

“…Regarding GC, the overexpression and exposure to exogenous GDF15 has been involved in the activation of different proliferative and invasive signals in tumor cell lines [29,30], whereas the GDF15 expression in primary tumors was correlated with progressive pathological parameters [31]. Finally, GDF15 levels were detected significantly increased in serum and plasma from GC patients versus healthy controls [32,33]. Increased GDF15 plasma levels were associated with poor survival in a pool of esophageal and GC patients including different histological subtypes, although without achieving prognostic independence [33].…”