Significance of microRNAs in predictive oncology: experimental and clinical observations in colorectal cancer, breast cancer and glioblastoma

SLABÝ, Ondřej, Marek SVOBODA, Pavel FABIAN, Milana ŠACHLOVÁ, Pavel FADRUS, Leoš KŘEN, Kateřina SOBKOVÁ, Dalibor VALÍK, Jaroslav MICHÁLEK a Rostislav VYZULA. Significance of microRNAs in predictive oncology: experimental and clinical observations in colorectal cancer, breast cancer and glioblastoma. In Abstract Book of the The 5th Symposium & Workshop on Molecular Pathology and Histo(cyto)chemistry. 2009. vyd. Olomouc: The Czech Society of Pathologists CLS JEP, 2009, s. 22-22. ISBN 978-80-87327-07-4.

Základní údaje

• Originální název: Significance of microRNAs in predictive oncology: experimental and clinical observations in colorectal cancer, breast cancer and glioblastoma
• Název česky: Significance of microRNAs in predictive oncology: experimental and clinical observations in colorectal cancer, breast cancer and glioblastoma
• Autoři: SLABÝ, Ondřej, Marek SVOBODA, Pavel FABIAN, Milana ŠACHLOVÁ, Pavel FADRUS, Leoš KŘEN, Kateřina SOBKOVÁ, Dalibor VALÍK, Jaroslav MICHÁLEK a Rostislav VYZULA.
• Vydání: 2009. vyd. Olomouc, Abstract Book of the The 5th Symposium & Workshop on Molecular Pathology and Histo(cyto)chemistry, od s. 22-22, 1 s. 2009.
• Nakladatel: The Czech Society of Pathologists CLS JEP

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Stať ve sborníku
• Obor: 30200 3.2 Clinical medicine
• Stát vydavatele: Řecko
• Utajení: není předmětem státního či obchodního tajemství
• Organizační jednotka: Lékařská fakulta
• ISBN: 978-80-87327-07-4
• Klíčová slova anglicky: microRNA; colorectal cancer; breast cancer; glioblastoma
• Štítky: breast cancer, Colorectal cancer, Glioblastoma, microRNA
• Příznaky: Mezinárodní význam

Anotace

MicroRNAs (miRNAs) are short (18-25 nucleotides in length) noncoding RNA molecules that post-transcriptionally regulate gene expression. Bioinformatic tools predict that miRNAs are able to regulate approximately one-third of mammalian genes, including a significant number of oncogenes, tumor suppressor genes and genes associated with the invasion, dissemination and chemoresistance of tumors. In our colorectal cancer study, we examined by real-time PCR expression levels of miR-21, miR-31, miR-143, miR-145 and let-7a-1 in bioptic samples of 35 colorectal cancer (CRC) patients including 5 cases of IUCC Stage I, 13 of Stage II, 8 of Stage III, 9 of Stage IV. For 6 cases of CRC samples also adjacent non-tumor tissue was analyzed. The expression levels of all tested miRNAs significantly differ in tumor and normal mucosa, miR-21 (p=0,0001) and miR-31 (p=0,0006) were up-regulated and miR-143 (p=0,013) and miR-145 (p=0,018) were down-regulated in tumors. miR-21 was also correlated with CRC stage. High expression of miR-21 was associated with lymph node positivity (p = 0,025), development of distant metastases (p = 0,009) and also with a poor survival (long-rank p=0,043) in CRC patients. Tumors with down-regulated miR-143 and miR-145 were bigger and more frequent (not significantly) in proximal CRC. In the case of glioblastoma, we examined the expression levels of miR-21, miR-221, miR-222, miR-181a-c, miR-125b and miR-128a in 22 primary glioblastomas and six specimens of adult brain tissue by Real-Time PCR method. In addition, we examined the methylation status of MGMT (O6-methylguanine-DNA methyltransferase) promoter by methylation-specific RT-PCR, as this has previously been shown to be a predictive marker in glioblastomas. MGMT status and microRNA expression levels were tested for any association with the patients response to concomitant chemoradiotherapy with temozolomide (RT/TMZ). MGMT methylation status was not correlated with age, gender, performance status, expression level of any microRNA analyzed and, most importantly, with response to RT/TMZ. Patients who responded to RT/TMZ tended to have lower expression levels of microRNA-181 family members than those with progressive disease. MiR-181b and miR-181c were significantly down-regulated in patients with a response to treatment (p=0,016; p=0,047, respectively) in comparison to patients with progressive disease. The "basal-like" mammary carcinomas occur in 15% of breast cancer with higher frequency in patients with altered BRCA1. Typical invasive "basal-like" carcinoma is characterized by triple negative phenotype (ER, PR and HER2 negative) and higher frequency of mutations in tumor suppressor p53. It seems probable, that alterations in the apoptotic p53-signaling pathways are one of the causal events in the pathogenesis of this molecular subtype of breast cancer. In our study of the "basal-like" mammary carcinoma we focused on the significance of miR-34a-c family known to be under direct transcriptional control of p53. Results of this study will be part of our presentation. This work was supported by grant IGA MZ NS 9814-4/2008, NR/9076 - 4 of the Czech Ministry of Health and Project No. MZ0MOU2005 of the Czech Ministry of Health .

Anotace česky

MicroRNAs (miRNAs) are short (18-25 nucleotides in length) noncoding RNA molecules that post-transcriptionally regulate gene expression. Bioinformatic tools predict that miRNAs are able to regulate approximately one-third of mammalian genes, including a significant number of oncogenes, tumor suppressor genes and genes associated with the invasion, dissemination and chemoresistance of tumors. In our colorectal cancer study, we examined by real-time PCR expression levels of miR-21, miR-31, miR-143, miR-145 and let-7a-1 in bioptic samples of 35 colorectal cancer (CRC) patients including 5 cases of IUCC Stage I, 13 of Stage II, 8 of Stage III, 9 of Stage IV. For 6 cases of CRC samples also adjacent non-tumor tissue was analyzed. The expression levels of all tested miRNAs significantly differ in tumor and normal mucosa, miR-21 (p=0,0001) and miR-31 (p=0,0006) were up-regulated and miR-143 (p=0,013) and miR-145 (p=0,018) were down-regulated in tumors. miR-21 was also correlated with CRC stage. High expression of miR-21 was associated with lymph node positivity (p = 0,025), development of distant metastases (p = 0,009) and also with a poor survival (long-rank p=0,043) in CRC patients. Tumors with down-regulated miR-143 and miR-145 were bigger and more frequent (not significantly) in proximal CRC. In the case of glioblastoma, we examined the expression levels of miR-21, miR-221, miR-222, miR-181a-c, miR-125b and miR-128a in 22 primary glioblastomas and six specimens of adult brain tissue by Real-Time PCR method. In addition, we examined the methylation status of MGMT (O6-methylguanine-DNA methyltransferase) promoter by methylation-specific RT-PCR, as this has previously been shown to be a predictive marker in glioblastomas. MGMT status and microRNA expression levels were tested for any association with the patients response to concomitant chemoradiotherapy with temozolomide (RT/TMZ). MGMT methylation status was not correlated with age, gender, performance status, expression level of any microRNA analyzed and, most importantly, with response to RT/TMZ. Patients who responded to RT/TMZ tended to have lower expression levels of microRNA-181 family members than those with progressive disease. MiR-181b and miR-181c were significantly down-regulated in patients with a response to treatment (p=0,016; p=0,047, respectively) in comparison to patients with progressive disease. The "basal-like" mammary carcinomas occur in 15% of breast cancer with higher frequency in patients with altered BRCA1. Typical invasive "basal-like" carcinoma is characterized by triple negative phenotype (ER, PR and HER2 negative) and higher frequency of mutations in tumor suppressor p53. It seems probable, that alterations in the apoptotic p53-signaling pathways are one of the causal events in the pathogenesis of this molecular subtype of breast cancer. In our study of the "basal-like" mammary carcinoma we focused on the significance of miR-34a-c family known to be under direct transcriptional control of p53. Results of this study will be part of our presentation. This work was supported by grant IGA MZ NS 9814-4/2008, NR/9076 - 4 of the Czech Ministry of Health and Project No. MZ0MOU2005 of the Czech Ministry of Health .