Cancer Biomarkers

The macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the transforming growth factor-β (TGF-β) superfamily that can serve as a potential immune-therapeutic target and/or a prognostic biomarker for the treatment of some cancers. This article reviews the current published data on the molecular and clinical application of MIC-1 in cancer.

Literature review was conducted using Medline, PubMed, Embase and Cochrane databases.

MIC-1 is the only known secreted p53-regulated cytokine and therefore can serve as a biomarker for p53 activation both in vitro and in vivo. MIC-1 gene can be activated by cyclooxygenase inhibitors and has pro-apoptotic and anti-tumour activities. Although MIC-1 may induce anti-tumour role in the early stages of cancer, it can promote the invasiveness and metastatic behaviour in advanced stages. Greater concentration of MIC-1 was associated with the induction of cancer-related anorexia and weight loss in animals and humans. Of clinical interest, MIC-1 out-performs all available biomarkers including CA19-9 in the differentiation of patients with resectable pancreatic cancer from patients with benign pancreatic disease. MIC-1 gene was over-expressed in colorectal cancer (CRC), and a progressive rise of MIC-1 serum levels was noted in patients with adenomatous polyps and further in patients with CRC.

MIC-1 cytokine has the potential characteristics for a new diagnostic biomarker and a target for cancer treatment. Further research however is required to characterise MIC-1 receptors and to revalidate its diagnostic power in larger and better-standardised clinical studies.

This study was intended to determine the diagnostic significance of signal peptide-CUB-EGF domain-containing protein 1 (SCUBE 1) levels in gastric cancer.

This retrospective study was conducted with patients with gastric cancer. SCUBE 1 titers of plasma in patients with gastric cancer were determined using an enzyme-linked immunosorbent assay (ELISA).

SCUBE 1 titers of gastric cancer patients were significantly higher compared with the control group (P=0.0001). At a SCUBE 1 cut-off point of 43 ng/mL, sensitivity was 67%, specificity 91%, positive predictive values (PPV) 92% and negative predictive values(NPV) 63%. SCUBE 1 levels of patients with methastase were not different from patients without methastase (P> 0.05).

SCUBE 1 levels in patients with gastric cancer were found higher compared to healthy subjects.

As key molecules that drive progression and chemoresistance in gastrointestinal cancers, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (Her2) have become efficacious drug targets in this setting. But until now, although above studies suggested that EGFR and Her2 may serve as effective biomarkers for targeted therapy in cancer patients with primary tumor, the information on these biomarkers in colorectal cancer is still limited in metastases.

The purpose of this study is to evaluate the expression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (Her2) on the lymph node metastasis (LNM) of colorectal cancer (CRC), develop LNM-associated biomarkers for CRC.

Differences in EGFR and Her2 expression between primary CRC with LNM (LNM CRC) and without LNM (non-LNM CRC) were assessed in a total of 126 Chinese colorectal carcinoma samples using quantitative real-time PCR analysis and western blot. Confirmation assay with immunohistochemistry (IHC) study was applied in the same samples. The relationship to clinicopathological parameters and prognosis of candidate biomarkers was also examined in the same samples.

EGFR and Her2 were significantly upregulated in LNM CRC compared to non-LNM CRC, which was confirmed by real-time quantitative polymerase chain reaction, western blot. Similar results were confirmed in the immunohistochemistry (IHC) assay. Overexpression of EGFR and Her2 were significantly associated with LNM (P < 0.001), advanced TNM stage (P < 0.001), increased 5-year recurrence rate (P < 0.001) and decreased 5-year overall survival rate (P < 0.001). Univariate and multivariate analyses indicated that EGFR and Her2 expression were useful independent prognostic factor for recurrence and survival of CRC patients (P < 0.05).

EGFR and Her2 might serve as a potential biomarker for LNM and a prognostic factor in CRC. Over-expression of EGFR or Her2 is a potential predict factor to the poor outcome in clinical colorectal cancer.