A novel stop codon mutation in STK11 gene is associated with Peutz-Jeghers Syndrome and elevated cancer risk: a case study.

Based on the analysis of patients with Peutz-Jeghers syndrome (PJS), Serine threonine kinase11 (STK11) is known as a tumor suppressor gene, which is involved in cell polarization, regulation of apoptosis, and DNA damage response. In this case report study, we examined STK11 gene sequencing in a 42-year-old woman with mucocuta neous pigmentation and positive family history. Endoscopy and colonoscopy showed >1000 polyps throughout the stomach/colon (PJ-type hamartomas). The larger polyp in the stomach was resected and the small bowel imaging detected multiple jejunum/ileum small polyps. The data released from the sequencing results revealed five alterations in exons 1 to 5. The major mutation in stop codon was reported as converted to the amino acid tryptophan (TRP) to tyrosine (TER). The TGG codon was converted to TAG by mutation. Finally, another novel mutation in STK11 stop codon as a 'de novo' variant was seen. It is predicted that stop codon mutations make the affected person susceptible to developing colorectal cancer.

Integrated bioinformatics and wet-lab analysis revealed cell adhesion prominent genes CDC42, TAGLN and GSN as prognostic biomarkers in colonic-polyp lesions.

Colorectal cancers are derived from intestinal polyps. Normally, alterations in cell adhesion genes expression cause deviation from the normal cell cycle, leading to cancer development, progression, and invasion. The present study aimed to investigate the elusive expression pattern of CDC42, TAGLN, and GSN genes in patients with high and low-risk polyp samples, and also colorectal cancer patients and their adjacent normal tissues. In upcoming study, 40 biopsy samples from Taleghani Hospital (Tehran, Iran) were collected, consisting of 20 colon polyps and 20 paired adjacent normal tissues. The expression of the nominated genes CDC42, TAGLN, and GSN was analyzed using quantitative polymerase chain reaction (Q-PCR) and relative quantification was determined using the 2-ΔΔCt method. ROC curve analysis was performed to compare high-risk and low-risk polyps for the investigated genes. The expression of adhesion molecule genes was also evaluated using TCGA data and the correlation between adhesion molecule gene expression and immunophenotype was analyzed. The role of mi-RNAs and lncRNAs in overexpression of adhesion molecule genes was studied. Lastly, GO and KEGG were performed to identify pathways related to adhesion molecule genes expression in healthy, normal adjacent, and COAD tissues. The results showed that the expression patterns of these genes were significantly elevated in high-risk adenomas compared to low-risk polyps and normal tissues and were associated with various clinicopathological characteristics. The estimated AUC for CDC42, TAGLN, and GSN were 0.87, 0.77, and 0.80, respectively. The study also analyzed COAD cancer patient data and found that the selected gene expression in cancer patients was significantly reduced compared to high-risk polyps and healthy tissues. Survival analysis showed that while the expression level of the GSN gene had no significant relationship with survival rate, the expression of CDC42 and TAGLN genes did have a meaningful relationship, but with opposite effects, suggesting the potential use of these genes as diagnostic or prognostic markers for colorectal cancer. The present study's findings suggest that the expression pattern of CDC42, TAGLN, and GSN genes was significantly increased during the transformation of normal tissue to polyp lesions, indicating their potential as prognostic biomarkers for colorectal polyp development. Further results provide valuable insights into the potential use of these genes as diagnostic or prognostic markers for colorectal cancer. However, further studies are necessary to validate these findings in larger cohorts and to explore the underlying mechanisms of these genes in the development and progression of colorectal cancer.

Non-coding RNAs in Precursor Lesions of Colorectal Cancer: Their Role in Cancer Initiation and Formation.

Colorectal cancer (CRC) is one of the world's most common types of malignancy. The proliferation of precancerous lesions causes this type of cancer. Two distinct pathways for CRC carcinogenesis have been identified: the conventional adenoma-carcinoma pathway and the serrated neoplasia pathway. Recently, evidence has demonstrated the regulatory roles of noncoding RNAs (ncRNAs) in the initiation and progression of precancerous lesions, especially in the adenoma-carcinoma pathway and serrated neoplasia pathway. By expanding the science of molecular genetics and bioinformatics, several studies have identified dysregulated ncRNAs that function as oncogenes or tumor suppressors in cancer initiation and formation by diverse mechanisms via intracellular signaling pathways known to act on tumor cells. However, many of their roles are still unclear. This review summarizes the functions and mechanisms of ncRNAs (such as long non-coding RNAs, microRNAs, long intergenic non-coding RNAs, small interfering RNAs, and circRNAs) in the initiation and formation of precancerous lesions.

Paracrine signals of mesenchymal stem cells induce epithelial to mesenchymal transition in gastric cancer cells.

AIM: Given the high similarity of phenotypical and secretory properties of mesenchymal stem cells and fibroblasts, this study investigated the possibility of inducing EMT process by mesenchymal stem cells. BACKGROUND: Annually, more than 13% of deaths worldwide occur due to cancer. One of the main reasons for the high mortality rate is due to the metastasis of cancer stem cells. Induction of metastasis occurs during the EMT process, which can also be stimulated by fibroblast cells. METHODS: Mesenchymal stem cells (MSCs) were isolated and sub-cultured until passage 3 or 4. AGS cells were co-cultured with MSCs for 4 days. As the positive control group, AGS cells were treated with TGF-ß (10ng/ml) for 48h. Finally, the mRNA expression level of Vimentin, ß-catenin, Snail, and E-cadherin as the EMT pattern, were evaluated by RT-PCR technique. RESULTS: Our findings indicated that AGS cells' crosstalk with MSCs significantly upregulated fibroblast markers including Vimentin and Snail expression. However, no significant changes were identified for ß-catenin gene expression. Additionally, AGS treatment with MSCs resulted in diminished E-cadherin in the targeted cells. CONCLUSION: Based on the results, the AGS cells crosstalk with MSCs activates induction of epithelial mesenchymal transition, which is confirmed through the elevation of Vimentin and Snail expression and reduction of E-cadherin expression as a specific epithelial marker. However, it seems that MSc was not effective on Wnt/ ß-catenin signal gastric cancer cell line.

Prevalence of binary-toxin genes (cdtA and cdtB) among clinical strains of Clostridium difficile isolated from diarrheal patients in Iran.

AIM: In this study we investigated the prevalence of binary toxin genes, cdtA and cdtB, in clinical isolates of C. difficile from hospitalized patients with diarrhea. BACKGROUND: C. difficile binary toxin (CDT) is an action-specific ADP-ribosyltransferase that is produced by some strains of C. difficile. Co-expression of this toxin with tcdA and tcdB can lead to more severe disease in CDI patients. METHODS: Totally, 930 patients suspected of having CDI was included in this study. All samples were treated with methanol and cultured on selective C. difficile agar plates. The C. difficile isolates were further identified by PCR. Presence of tcdA, tcdB, cdtA, and cdtB genes among the strains were examined by PCR. RESULTS: Analysis of the PCR results showed a prevalence of 85.2% (144/169) for toxigenic C. diffidile. Toxin genotyping of the strains for tcdA and tcdB genes revealed the toxin profiles of A+B+, A+B-, A-B+ accounting for 86.1% (124/144), 7.6% (11/144), 6.2% (9/144) among the strains, respectively. Totally, 12.4% (21/169) of the C. difficile strains were binary toxin-positive. cdtA-B+, cdtA+ B + and cdtA+B- were detected in 43% (9/21), 38% (8/21) and 19% (4/21) of the strains, respectively. Interestingly, 12% (3/25) of nontoxigenic C. difficile strains (tcdA-B-) had either cdtA+ B + or cdtA-B+ profiles. CONCLUSION: This is the first report for the prevalence of binary toxin genes in C. difficile strains isolated from Iran. Further studies are required to investigate the exact role of binary toxins in the pathogenesis of C. difficile particularly in patients with chronic diarrhea among Iranian populations.