Cancer Biomarkers

The prevalence of EGFR, KRAS, BRAF and PIK3CA somatic mutations in 861 randomly selected Chinese patients with non-small cell lung cancer (NSCLC) was assayed by the SurPlex®-xTAG70plex platform and analyzed. The results showed that the occurrence rates were 41.0, 8.0, 0.7 and 3.7%, respectively. The mutation rates significantly correlated with gender, histology and smoking history. The EGFR exon 19, 20 and 21 mutations were higher in females compared to males (p< 0.001, exon 19 and 21; p=0.018, exon 20), higher in adenocarcinomas compared to other forms of lung cancers (p< 0.001, exon 19 and 21; p=0.035, exon 20), and higher in non-smokers compared to smokers (p< 0.001, exon 19 and 21; p=0.029, exon 20). Conversely, the KRAS mutations were higher in males compared to females (p=0.004), higher in adenocarcinomas compared to other forms of lung cancers (p< 0.001), and higher in smokers compared to non-smokers (p< 0.001). The PIK3CA mutation rate was lower in adenocarcinomas compared to other forms of lung cancers (p=0.003).

The detection of circulating tumor cells (CTCs) has received great attention. MicroRNA-21 (miR-21) plays crucial roles in carcinogenesis and is considered as one of the most studied oncomiRNAs. We determined if miR-21 could be used a marker for the detection of CTCs in gastric cancer patients. Peripheral blood samples were collected from 53 preoperative patients with gastric cancer and 20 healthy volunteers. Real-time reverse transcription-polymerase chain reaction was used to detect the level of miR-21. Receiver operator characteristic curves (ROC) were constructed. Patients with gastric cancer display a significantly higher level of miR-21 in peripheral blood than those from controls. The miR-21 level was associated with the tumor node metastasis (TNM) stage, tumor size and tissue categories. The area under ROC curve was up to 0.853 ± 0.086. This study highlights the potential of the detection of miR-21 in peripheral blood as a novel tool for monitoring CTCs in gastric cancer patients.

Synchronous or metachronous brain metastases (BMs) occur in about 33% of patients affected by non-small-cell lung cancer (NSCLC). To date, no reliable biological marker is able to identify patients who will develop BMs. In the present study, using a quantitative double-labeling immunofluorescence analysis, we evaluated the expression of chemokine CXCL12 and its receptor, CXCR4, in primary NSCLC histological specimens of patients with and without BMs. The immunoreactivity of CXCL12 and CXCR4 was significantly higher in NSCLC samples of patients with BMs. We performed Receiver Operating Characteristics (ROC) analysis in order to define optimal cut-off values for CXCL12 and CXCR4 immunoreactivity that could discriminate between NSCLC patients without and with BMs. ROC curves showed a good diagnostic accuracy and adequate predictive power for both CXCL12 and CXCR4. These findings suggest a possible role for the CXCL12/CXCR4 axis in the metastatic evolution of NSCLC, and its potential use as prognostic markers and drug targets.

Prostate cancer (Pca) is the most common form of cancer affecting men, despite recent advances in PCa treatments, one third of patients diagnosed each year succumb to this disease. The inflammatory response has been implicated in prostate cancer progression. The pro-inflammatory transcription factor, NFκB/p65 has been implicated in PCa progression. Few studies have examined the involvement of NFκB and inflammatory signalling in PCa.

Immunohistochemistry was employed to investigate the expression of NFκB/p65, C-reactive protein and Ki67 in 61 clinical samples.

Tumours expressing high levels of p65 (p=0.004), CRP (p=0.011) and Ki67 (p=0.0003) had a shorter disease specific survival. Upon combining p65 and CRP status it was observed that those tumours with low expression of both proteins had a median survival of 11 years compared to 3.9 years for those with tumours with high expression of both (p=0.005). CRP expression was significantly higher in the 21 patients who died of their disease and on multivariate analysis CRP expression retained independent significance (p=0.005).

This study suggests CRP and NFκB may function collectively to drive prostate cancer progression in a subset of patients. Tumoral CRP is a significant independent predictor of cancer specific survival. The relationship between tumour CRP and signalling pathways warrants further investigation in a larger cohort.

In the present study, the human orthologue of the secreted Xenopus laevis anterior gradient 2 (AGR2) protein was evaluated as a potential serum biomarker of lung adenocarcinoma. AGR2 protein levels were preoperatively measured in the serum of 111 primary lung adenocarcinoma patients and in 46 non-cancer controls with subsequent calculation of sensitivity and specificity in comparison with serum CEA levels. Correlations with clinicopathological variables were also assessed and survival analyses were performed according to the Kaplan-Meier method and differences determined with the log-rank test. The mean serum AGR2 level of lung adenocarcinoma patients in each stage, even Stage I, was significantly higher than in non-cancer controls (P < 0.001 for all stages, Mann-Whitney U test). The sensitivity was 65.8% (52.9% for stage IA), even higher than that of CEA, which was 45.0% (29.4% for stage IA), and the specificity was 87.0% according to the ROC curve (AUC=0.858). Positive serum AGR2 expression was significantly associated with the incidence of recurrence after surgery (P=0.025) and with a poor prognosis (P=0.037 for overall survival and P=0.004 for disease-free survival). Preoperative serum AGR2 might become a clinically useful biomarker for early detection, prediction of recurrence and prognosis with lung adenocarcinomas.