Macrophage Inhibitory Cytokine-1 as Biomarker of Pancreatic Cancer

Several studies have demonstrated that the macrophage inhibitory cytokine-1 (MIC-1) may be a powerful diagnostic biomarker in patients with pancreatic cancer, but some studies are inconclusive. A metaanalysis pooled data from selected studies to yield sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), and receiver operating characteristic (SROC) curve (Chen et al. 2014). The results revealed that serum MIC-1 levels in pancreatic patients were higher than those of healthy subjects. The area under the SROC curve was 0.92; the pooled sensitivity was 0.79; and the pooled specificity was 0.86. The pooled positive LR was 6.20; and the pooled DOR was 35.73. Thus serum MIC-1 may be a useful diagnostic biomarker with high sensitivity and specificity for identifying pancreatic cancer.

Proteomic Biomarkers of Pancreatic Cancer

Expression Difference Mapping experiments with serum samples from patients with pancreatic adenocarcinoma compared to those with non-malignant pancreatic diseases and healthy controls have shown that the discriminative power of the resulting biomarker panels was superior to the established CA19-9 marker and the best results were achieved by using combined panels of SELDI markers together with CA19-9.

In conventional practice, the use of CA 19-9 levels and imaging techniques is not optimal for detecting small pancreatic lesions. New experimental approaches, such as quantitative proteomics, have shown great potential for the study of cancer and have opened new opportunities to investigate crucial events underlying pancreatic tumorigenesis and to exploit this knowledge for early detection and better intervention. Isotope-coded affinity tag technology for proteomic analysis of human cancer tissue has been used to identify differentially expressed proteins in pancreatic cancer.

A specific cell receptor, the RON receptor tyrosine kinase, is a member of the MET proto-oncogene family and is important for cell proliferation, differentiation, and cancer development. RON receptor is overexpressed in pancreatic cancer cells suggesting that the receptor may also contribute to the disease’s development (Thomas et al. 2007). RON receptor was active in 93% of pancreatic intraepithelial neoplasia, an early form of pancreatic duct cancer. In addition, the receptor was present in 79% of primary pancreatic cancers and 83% of metastatic cancers. RON receptor’s signaling pathways could be a key factor contributing to pancreatic cancer progression. If the receptor could be blocked, it would provide a new target for RON-directed therapies that are more effective in treating this cancer.

One study has searched for pancreatic cancer biomarkers by use of high- resolution MS and acrylamide isotopic labeling in the plasma proteome of mice genetically engineered to develop cancers that closely resemble human pancreatic tumors (Faca et al. 2008). Finally, using blood samples collected during a clinical trial, the Carotene and Retinol Efficacy Trial (a cancer-prevention study), the researchers showed that the measurement of five of the proteins present in increased amounts at an early stage of tumor development in the mouse model discriminated between people with pancreatic cancer and matched controls up to 13 months before cancer diagnosis. Such proteins could be used in screening blood tests for early and more accurate detection of cancer.

Concluding Remarks on Biomarkers of Pancreatic Cancer

There are several diagnostic methods available to pancreas including CT scan, gadolinium-enhanced MRI, magnetic resonance cholangiopancreatography and endoscopic ultrasound. However, the most promising method is endoscopic ultrasound-guided fine-needle aspiration as this technique enables analysis of cyst fluid using biomarkers (Moris et al. 2017). Previously two biomarkers were available in clinical practice: carcinoembryonic antigen and carbohydrate antigen 19-9. Now DNA analysis of pancreatic cystic fluid and genomic analysis may provide new tools for the diagnosis. Novel genomic and serum biomarkers could play an important future role to identify those individuals who will benefit from an early operation and those who will benefit from watchful waiting approach.

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