Evaluating macrophage migration inhibitory factor 1 expression as a prognostic biomarker in colon cancer

Abstract

Objective: Several studies indicate that macrophage migration inhibitory factor 1 plays a role for tumor progression in colon cancer. We investigated whether determination of migration inhibitory factor 1 mRNA expression levels in lymph nodes of colon cancer patients could be used as a prognostic marker. Methods: Expression levels of migration inhibitory factor 1 and carcinoembryonic antigen mRNAs were assessed in primary tumors and regional lymph nodes of 123 colon cancer patients (stages I–IV), and in colon cancer- and immune cell lines using quantitative reverse transcriptase–polymerase chain reaction. Expression of migration inhibitory factor 1 protein was investigated by two-color immunohistochemistry and immunomorphometry. Results: Migration inhibitory factor 1 mRNA was expressed at 60 times higher levels in primary colon cancer tumors compared to normal colonic tissue (medians 8.2 and 0.2 mRNA copies/18S rRNA unit; p < .0001). A highly significant difference in mRNA expression levels was found between hematoxylin-eosin positive lymph nodes and hematoxylin-eosin negative lymph nodes (p < .0001). Migration inhibitory factor 1 and carcinoembryonic antigen proteins were simultaneously expressed in many colon cancer-tumor cells. Kaplan–Meier survival model and hazard ratio analysis, using a cutoff level at 2.19 mRNA copies/18S rRNA unit, revealed that patients with lymph nodes expressing high levels of migration inhibitory factor 1 mRNA had a 3.5-fold (p = .04) higher risk for recurrence, associated with a small, but significant, difference in mean survival time (7 months, p = .03) at 12 years of follow-up. Conclusion: Although migration inhibitory factor 1 mRNA expression levels were related to severity of disease and lymph node analysis revealed that colon cancer patients with high levels had a shorter survival time after surgery than those with low levels, the difference was small and probably not useful in clinical practice.

Prognostic Significance of GPR55 mRNA Expression in Colon Cancer

“…We found that low levels of GPR55 mRNA was associated with poor prognosis. The finding contrasts with the results for all other biomarker mRNAs that we have studied so far, i.e., CEA, CXL17, CXCL16, LGR5, LGR4, GPR35V2/3 and EpCAM [10,[12][13][14][15][16][17], for which high levels were associated with poor prognosis. Notably, this reverse correlation was only found in lymph nodes.…”

Clinical Significance of Stem Cell Biomarkers EpCAM, LGR5 and LGR4 mRNA Levels in Lymph Nodes of Colon Cancer Patients

“…Afterwards, the sections were incubated with FITC-conjugated BerEP4 (green) (mouse IgG1, clone BerEP4, F0860; Dako). Double-positive cells show a yellow-orange color, as previously described [ 33 ]. Mouse IgG, ready to use (Dako) and FITC-conjugated anti-mouse (F0313; Dako) were used as negative controls.…”

MIF-Dependent Control of Tumor Immunity

“…The extent of MIF expression is dependent on the tumor tissue type, stage, and grade among other factors (10). For example, intratumoral MIF is increased-versus normal tissue-three-and five-fold in endometrial carcinoma and non-small cell lung carcinoma (11,12), respectively, ten times in hepatocellular carcinoma (13) and sixty times in colorectal cancer (14). In hepatocellular carcinoma, a positive correlation was also identified between intratumoral MIF and plasma MIF, suggesting that high tumor-associated MIF expression may drive higher circulating levels of soluble MIF (13).…”