The methylation of arginine has been implicated in many cellular processes, such as regulation of transcription, mRNA splicing, RNA metabolism and transport. The enzymes responsible for this modification are the protein arginine methyltransferases. The most abundant methyltransferase in human cells is protein arginine methyltransferase 1. Methylation processes appear to interfere in the emergence of several diseases, including cancer. During our study, we examined the expression pattern of protein arginine methyltransferase 1 gene in colon cancer patients. The emerging results showed that the expression of one of the gene variants is associated with statistical significant probability to clinical and histological parameters, such as nodal status and stage. This is a first attempt to acquire an insight on the possible relation of the expression pattern of protein arginine methyltransferase 1 and colon cancer progression.

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Several members of the human tissue kallikrein-related peptidase (KLK) family are emerging cancer biomarkers. The aim of this study was to analyse the expression of a panel of KLKs in colorectal cancer and to find out if the multiparametric combination of them can increase the accuracy of prediction of patients survival beyond the traditional clinical information. Nine KLKs (KLK5-8, KLK10, KLK11, KLK13-15) were measured using ELISA assays in cytosolic extracts of 122 colon cancer tissues and their nearby normal mucosa, obtained during surgery. The mean levels of almost all KLKs in tumour tissues were significantly different from their counterparts of normal tissue (Po0.0001). KLK 5, 6, 7, 13, 14 were significantly associated with overall survival in univariate analysis, but after adjusting for age, TNM and differentiation stage, only KLK5 (HR: 1.24 (95% CI: 1.05 -1.47)), KLK7 (HR: 1.57 (95% CI: 1.04 -2.37)) and KLK14 (HR: 1.43 (95% CI: 1.05 -1.94)) remained significant. Addition of a panel of selected KLK markers to clinical parameters gave an increment in AUC of 0.86 beyond the clinical factors at year 1, showing that it can increase the accuracy of prediction of overall survival beyond the traditional clinical information, particularly the short-term (1 year) survival after surgery.

Apoptosis is an active process regulated by a variety of genes. Recently, the molecular cloning, physical mapping and expression analysis of a novel gene of the Bcl-2 family, BCL2L12, was reported. Expression analysis of the BCL2L12 gene in breast cancer confirmed an association of BCL2L12 with favorable prognosis of patients. In the present study, the expression of the BCL2L12 gene was analyzed in colon cancer by RT-PCR. Two transcripts, BCL2L12 and BCL2L12-A, were overexpressed in the cancer tissues as compared to their paired normal mucosa. An association was found between BCL2L12-A transcript expression and nodal status, as well as Dukes' stage. The BCL2L12-A transcript appears to be of importance for colon cancer since its expression is associated with disease progression.

Currently available colon cancer (CC) markers lack sensitivity and specificity. Kallikrein-related peptidases (KLKs) present a new class of biomarkers under investigation for diverse diseases, including cancer. KLKs are co-expressed in various tissues participating in proteolytic cascades. KLK7 in human tumours facilitates metastasis by degrading components of the extracellular matrix. KLK14 promotes tumourigenesis by activating proteinase-activated receptors. In the present study we examined the concomitant expression of KLK7 and KLK14 in245 colonic tissue specimens from 175 patients; 70 were pairs of cancerous-normal tissues, 31 were cancerous tissues and 74 were colonic adenomas. We used quantitative real-time PCR and proved that both genes are up-regulated in CC at the mRNA level. Receiver-operating characteristic (ROC) analysis of our results showed that both genes have discriminatory value between CC and adenoma tissues, with KLK14 obtaining greater distinguishing power (area under the curve [AUC]=0.708 for KLK14; AUC=0.669 for KLK7). Current work showed that the two genes are fairly co-expressed in all three types of colon tissues examined (normal rs=0.667, p<0.001, adenomas rs=0.373, p=0.001, carcinomas rs=0.478, p<0.001). KLK14 is associated with shorter disease-free survival (DFS) and overall survival (OS) of patients (p=0.003, p=0.016 respectively), whereas KLK7only with shorter DFS (p=0.004). KLK7 and KLK14 gene expression can be regarded as markers of poor prognosis for CC patients with discriminating power between CC and adenoma patients.