Comethylation of p16 and MGMT genes in colorectal carcinoma:Correlation with clinicopathological features and prognostic value

AIM: To investigate the significance of p16 and O6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT methylation status was examined on 47 tumor samples, and K-ras mutational status was examined on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS-PCR) method was used. RESULTS: p16 and MGMT promoter methylation was found in 51% (24/47) and 43% (20/47) of CRCs, respectively, and the K-ras mutation was found in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease within a two-year period of observation. Only 27% of patients with simultaneous p 16 and MGMT methylation showed the detectible occurrence of metastasis and/or death, compared to 67% of patients without double methylation or with no methylation (3/11 vs 22/33, P < 0.05, χ2-test). In addition, p16 and MGMT comethylation showed a trend toward an association with longer survival in patients with CRCs (35.5 ± 6.0 mo vs 23.1 ± 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a two-year period was observed in 66% of patients carrying the K-ras mutation, compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P < 0.001, χ2-test). The presence of the K-ras mutation significantly correlated to shortened overall survival (20.0 ± 1.9 mo vs 37.0 ± 1.8 mo, P < 0.001, Log-rank test). The comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease even when K-ras mutations were included in the analysis as an independent variable. CONCLUSION: Our data suggest that comethylation of promoters of p 16 and MGMT genes could have a prognostic value in patients with CRC. Specifically, concurrent methylation of both genes correlates with better prognosis.

circRNAs in drug resistance of breast cancer

Breast cancer(BC)is the most common heterogeneous disease in women and one of the leading causes of cancer-related death.Surgery,chemotherapy,radiotherapy,hormone,and targeted therapy are the gold standards for BC treatment.One of the significant challenges during the treatment of BC represents resistance to chemotherapeutics,resistance that severely limits the use and effectiveness of the drugs used for BC treatment.Therefore,it is essential to develop new strategies to improve therapeutic efficacy.Circular RNAs(circRNAs)are a large group of non-coding RNAs that covalently form closed circular loops by joining their 5′,and 3′;ends.Accumulating evidence suggests that circRNAs have a vital role in cancer development,progression,and BC resistance to chemotherapy.The purpose of this review is to discuss the biological properties of circRNAs,and how circRNAs induce resistance to conventional therapeutic anti-cancer drugs used in BC treatment,by emphasizing and summarizing the potential roles of circRNAs in mechanisms of drug resistance,such as drug efflux,apoptosis dysfunction,autophagy,and DNA damage repair.CircRNAs are associated with drug resistance via ATP-binding cassette(ABC)efflux transporters,while some others by inhibition of cell apoptosis,thus leading to resistance to tamoxifen in BC cells.In contrast,others are involved in the promotion of BC cells chemoresistance by doxorubicininduced autophagy.CircRNAs may have clinical significance in regulating or overcoming BC drug resistance and may give directions towards a novel approach to personalized BC treatment.CircRNAs may significantly contribute to the identification of new therapeutic targets for the prevention of BC chemoresistance.