Study On Telomerase And Its Related Factors In Colorectal

CHAPTERI PROGNOSTIC ROLE OF TELOMERASE ACTIVITY IN COLORECTAL ADENOCARCINOMA:A META-ANALYSISObjective:To investigate the relationship between telomerase activity and the clinical outcome of colorectal cancer.Methods:The published studies were searched in PubMed、EMBASE、 web of science、google scholar、CNKI、Wangfang databases from year 1989 to 2014 by meeting specified search criteria. Then the quality of the included trials was assessed and meta-analysis was performed by Revman 5.0 software. We used the odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association between telomerase activity and metastasis of colorectal cancer(CRC).Results:A meta-analysis of 17 studies (1015 patients) was performed to evaluate the association between telomerase activity and metastasis-related parameters in CRC patients.Our analysis results indicated that high telomerase activity expression tended to be associated with the presence of the depth of invasion (435 patients) (OR=2.40,95% CI=1.44-4.02, P=0.0008), lymph node metastasis (689 patients) (OR=3.28,95% CI=2.0-4.90, P<0.00001), distant metastasis (388 patients) (OR=2.09,95% CI=1.11-3.92, P=0.02) and TNM stage (995 patients) (OR=2.54,95% CI=1.82-3.55, P<0.00001). However, high TA expression was not associated with the presence of tumor size (530 patients) (OR=1.06,95%CI=0.71-1.57, P=0.78), histologic differentiation (671 patients) (OR=1.10,95%CI=0.55-2.20, P=0.79) and tumor site (631 patients) (OR=1.27,95%CI=0.85-1.91, P=0.24).Conclusion:telomerase overexpression not only plays a key role in primary initiation, but also promotes invasion and metastatic progression of CRC, These findings raise the possibility of using TA to screen for the prognosis of CRC.CHAPTER Ⅱ CLINIC AL AND PROGNOSTIC SIGNIFICANCE OF HTERT EXPRESSION IN PATIENTS WITH COLORECTAL CANCERObjective:To investigate the expression profile of human telomerase reverse transcriptase (hTERT) in colorectalcancer (CRC) and to assess its clinical significance.Methods:Quantitative real-time PCR was used to detect expression of hTERT mRNA both in colorectal cancer tissue and in corresponding normal distal mucosa. Expression data were correlated with Clinical pathological parameters, and we also performed survival analysis to evaluate the prognostic role of hTERT in CRC.Results:The hTERT mRNA was expressed in both tumor and CRC tissue, but it was expressed at significantly higher levels in cancer tissue (P= 0.011). Upregulation of hTERT was significantly associated with lymph node involvement (P=0.011) and TNM stage (P=0.006). Kaplan-Meier survival analysis of low vs. high expressers of hTERT revealed much lower survival among high expressers (P=0.014).Conclusions:The results of the current study suggest that hTERT may play an important role in onset of CRC, so the protein may have potential as a prognostic biomarker or even as a therapeutic target.CHAPTER Ⅲ CLINICAL AND PROGNOSTIC SIGNIFICANCE OF HTERT-TARGETING MIRNAS IN COLORECTAL CANCERObjective:To analyze the expression of tumor suppressor microRNAs (miRNAs) that potentially inhibit hTERT expression and to assess its clinical significance.Methods:In our research, the 8 miRNAs candidates (miR-29c-3p, miR-124-3p, miR-133a-3p, miR-133b, miR-138-5p, miR-150-5p, miR-378a-3p, miR-422a, respectively) with the potential to interact with hTERT were used from the result of our preliminary work. The expression of the 8 miRNAs candidates were verified by quantitative real-time polymerase chain reaction both in colorectal cancer tissues and in corresponding normal tissues. Expression data were correlated with Clinical pathological parameters. A survival analysis was used to assess the prognostic role of hTERT-targeting miRNAs in CRC.Results:The results of qRT-PCR revealed that the 7 miRNAs (miR-124-3p, miR-133a-3p, miR-133b, miR-138-5p, miR-150-5p, miR-378a-3p, miR-422a, all of P<0.000) expression level in colorectal cancer tissues were statistically significant down-regulated when compared with corresponding normal tissues. However, there was no significant difference in the levels of miR-29c-3p. Finally, low expression of miR-138-5p and miR-378a-3p was significantly associated with distant metastasis (P<0.000, P=0.008, respectively), while the low expression of miR-422a was significantly associated with lymph node involvement (P=0.008). Kaplan-Meier survival curves demonstrated high-expression group vs. low-expression group of miR-422a showed a statistical differences in CRC patients (P=0.024), which implys that down-regulated of miR-422a is associated with a poorer prognosis.Conclusion:The 7 hTERT-targeting miRNAs (miR-124-3p, miR-133a-3p, miR-133b, miR-138-5p, miR-150-5p, miR-378a-3p, miR-422a) were expressed at significantly lower levels in CRC. Our results also suggest a potential application of miR-422a in prognosis prediction and CRC treatment.CHAPTER IV THE ROLE OF MICRORNAS IN COLORECTAL CANCERMicroRNAs (miRNAs) are a class of newly discovered eukaryotes, highly conserved, a length of about (18-24) nt endogenous non-coding single-stranded RNA. They regulate various cellular processes such as proliferation, differentiation and apoptosis through suppressing their target genes. In recent years, studies have demonstrated that the altered expression pattern of mirnas is implicated in many forms of cancer as oncogenes and tumor suppressors, playing an important role in cancer occurrence, development and progression, especially in colorectal cancer (CRC). The relationship between aberrant expressions of miRNAs and CRC has become one of the current research focus. Here, this paper summarizes the potential role of miRNAs as biomarkers for diagnosis, prognosis and treatment of CRC.