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Long non-coding RNAs have been proposed as biomarkers for the detection, prevention and screening of various malignancies. In this study, two lncRNAs (ANRIL and BANCR) were assessed for biomarker application in the early detection of colorectal cancer (CRC) through stool specimen testing, as a non-invasive and cost-effective methodology. A total of 40 stool samples were collected from patients referred to the hospital with colorectal cancer or adenomatous polyps as pre-cancerous lesions; patients were diagnosed using colonoscopy and pathology reports were available. Twenty control samples were also obtained from healthy subjects for comparison. RNA extraction and cDNA synthesis were followed by real-time PCR to evaluate lncRNA expression. The up-regulation of ANRIL in 20% of samples taken from polyp patients, combined with up-regulation in 65% of patients with CRC, confirmed the potential usefulness of ANRIL as a prognostic biomarker (AUC 0.95; P0.0001). BANCR relative expression analysis illustrated significant up-regulation in polyp (P0.04) and tumoural participants (P0.03) compared with normal control individuals. The expression patterns of ANRIL and BANCR in polyp cases were significantly correlated according to correlation analysis (r = 0.45, P0.045). ANRIL expression patterns in stool specimens of polyp and tumour cases supported the use of ANRIL as a prognostic biomarker for screening patients in the early stages of CRC. Up-regulation of BANCR in pre-cancerous lesions as well as down-regulation of ANRIL may also be a specific marker pair for easy, convenient and fast CRC prognosis.

Background Long non-coding RNAs (LncRNAs) are known to have regulatory consequences for aberrant gene expression in cancers. The aim of this study was to evaluate the expression levels of long non-encoding RNAs, BACE1 (β-secretase1) and LINC-PINT (Long Intergenic Non-Protein Coding RNA, P53 Induced Transcript), in colorectal cancer (CRC) with clinicopathological parameters. Methods and results Bioinformatics analysis defining effectual signalling pathways Wnt. A total of 130 tissue samples (50 fresh CRC tissues with parallel adjacent normal tissues (ADJ) accompanied with 30 normal healthy control tissue samples) were collected from the Iranian population. mRNA expression analysis was performed via Real Time Q-PCR. Statistical analysis for comparing CRC expression levels with ADJ and normal healthy tissues were carried out using Kruskal–Wallis tests. The Receiver Operating Characteristic (ROC) curve was plotted for each LNC, separately. We discovered that PINT and BACE1 expression levels were decreased and increased respectively in CRC tumour samples compared with ADJ normal and healthy tissues. Clinicopathological parameter assessment revealed a significant relationship between PINT expression, tumour location, staging and distant metastasis (p Conclusion We investigated two LNCRNAs (PINT and BACE1) as potential CRC prognostic biomarkers, which are imperative for early and effective medical intervention in CRC. Expression levels of PINT and BACE1 in CRC tissue samples may serve to identify metastasis earlier, increasing patient survival rates and expediating clinical treatment options.

Clinicopathological features of high-frequency microsatellite instability (MSI-H) colorectal cancers (CRCs) are different from low-frequency MSI (MSI-L) and microsatellite stable (MSS) CRCs. The clinical features of MSI-L cases are unknown, and although the tumors usually show instability for dinucleotide markers, evaluation based on dinucleotides alone could lead to the misclassification of MSI-L or MSS as MSI-H. In this research, we investigated the usefulness of hypoxia-inducible factor-1α (HIF-1α) expression to discriminate MSI-L from MSS and MSI-H in human CRC. Tumor tissue from 94 CRC patients was used to determine the expression level of HIF-1α mRNA and HIF-1α protein using quantitative real-time PCR and immunohistochemistry analyses, respectively. The results indicated that HIF-1α mRNA and HIF-1α protein levels were upregulated in CRC patients compared with controls (P < 0.0001). Average HIF-1α expression in tissues with advanced stages and grades was also higher than that in earlier stages and grades. Expression of HIF-1α mRNA varied between CRC patients with different types of microsatellite instability (MSS, MSI-L and MSI-H). Taken together, our findings provide preliminary evidence that HIF-1α expression level in CRC tumors correlates with different MSI categories. HIF-1α expression may therefore represent a novel marker to separate the MSI-L group from the MSS and MSI-H groups.

Different molecular signaling pathways have been involved in the incidence and progression of CRC. We aimed to examine the correlation between eight candidate genes, including TFGβ, SMAD2, SMAD4, RhoA, EGFR, MAP2K1, MTA1, and LEF1 in the progression of colorectal cancer (CRC) and their association with clinicopathological variables and CRC patients prognosis. Immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) analysis 2

GJB2 mutation analysis is used routinely as a first step in genetic testing for autosomal recessive non-syndromic sensorineural hearing loss. Although most GJB2 mutations can be detected by sequencing of the exon 2 of this gene, a prevalent splice mutation, c.-23+1G>A (IVS1+1G>A), is not usually included in the analyzed region. In this study, we have developed an ARMS-PCR strategy for detection of this mutation among Iranian deaf individuals. A total of 418 Iranian individuals with hearing loss consistent with autosomal recessive non-syndromic sensorineural hearing loss based on audiological test result, medical history, physical examination and pedigree of the family, were included in this study. c.35delG and c.-23+1G>A mutations were detected by using ARMS-PCR. Direct sequencing of the exon 2 of the GJB2 gene was performed for mutation analysis of the coding region of this gene. Among 418 investigated cases, a total of 81 patients (~19.4 %) with biallelic pathogenic mutations in the GJB2 gene and 13 cases with only one pathogenic mutant allele were identified. The total allele frequencies of the two most frequent mutations, c.35delG and c.-23+1G>A, among mutated alleles were found to be around 59 and 15.7 %, respectively. High frequency of the c.35delG and c.-23+1G>A mutations among Iranian deaf individuals shows the importance of developing rapid and cost-effective methods for primary mutation screening methods before performing direct sequencing.