MicroRNA Profiles Distinguish Renal Cell Carcinomas
MicroRNA Profiles Distinguish Renal Cell Carcinomas
October 20, 2008 (Baltimore, Maryland) — The results of a new study analyzing the specific expression profiles of micro (mi)RNA in different categories of renal cancer indicate that the expression profiles are unique and different from one another.
The next goal is to use these results to look at potential therapeutic targets. "Once we are able to understand the expression profiles better for specific tumors — not just renal cancers, but all cancers — and identify how they actually affect gene regulation, that can help direct therapies," lead author Gary Tozbikian, MD, a second-year resident in the department of pathology at the University of Pennsylvania, in Philadelphia, said in an interview with Medscape Pathology.
"MiRNAs are unique molecules," said Dr. Tozbikian. "They are very short segments of RNA that do not actually encode for anything, but play a profound role in regulating gene expression, and they get perturbed in cancer."
"It is known that these miRNA molecules act as master switches, controlling gene expression, determining how tissues will behave," added Dr. Tozbikian. It is thought that by studying these molecules, scientists can understand more about tumor biology and find clues to outcomes for cancer patients.
"This is the first study of its kind," noted Dr. Tozbikian. The study focused specifically on renal cell carcinoma (RCC). However, a number of studies that have looked at these types of data in other cancers, including colon, breast, and lung, have found unique expression profiles for those tumors. "Some of those studies have even shown that the expression profiles have prognostic information, indicating, for example, that if certain miRNAs are upregulated, patients' outcomes are worse or they do not respond to chemotherapy," explained Dr. Tozbikian
The researchers have identified the unique miRNA profiles of chromophobe (CHRCC), papillary (PRCC), and clear cell carcinoma (CCRCC). They studied 25 cases of CHRCC, PRCC, and CCRCC. RNA was extracted from tumor and normal kidney-tissue samples that were formalin-fixed and paraffin-embedded.
The RNA was hybridized to a "very comprehensive 754 miRNA probes and wells microarray," noted Joel Shilling, MD, medical director of Quest Diagnostics, in Portland, Oregon, who commented on the study results in an interview with Medscape Pathology. "This is cutting-edge," added Dr. Shilling, who was not involved in the study.
Dr. Tozbikian and colleagues calculated a 1-way analysis of variance across all 3 groups. Only miRNAs with a change 3-fold or more with respect to normal kidney tissue were considered for the analysis, explained Dr. Tozbikian in his poster presentation. CCRCC was compared with PRCC, and CCRCC was compared with CHRCC, and the miRNAs were prioritized by degree of change and P value.
The study results showed that 7 miRNAs were upregulated more than 3-fold in CCRCC, whereas 20 were downregulated. In PRCC, 9 miRNAs were upregulated and 2 were downregulated. In CHRCC, 20 miRNAs were upregulated, with more than a 10-fold expression, and 3 were downregulated. A total of 9 miRNAs were differentially expressed between CHRCC and PRCC. The investigators confirmed the results by reverse-transcriptase polymerase chain reaction, using 6 probes for miRNA.
"We were successful in showing that a distinct subset of miRNAs is differentially expressed between the 3 categories of RCC tumors studied," concluded Dr. Tozbikian, adding that the data provide a strong rationale for further cohort studies "to evaluate the diagnostic utility of miRNAs in the classification of renal cell carcinoma."
"We face this problem in routine interpretation of biopsies, and here is a parameter that we can measure that would help the pathologist confirm the diagnosis," noted Dr. Shilling: "It will be a while until these results, if confirmed, willactually be in the pathology laboratory, but many of these novel microarrays are now coming down to the community hospital and pathology branch laboratory setting."
The study did not receive commercial support. Dr. Tozbikian and Dr. Shilling have disclosed no relevant financial relationships.
American Society for Clinical Pathology (ASCP) 2008 Annual Meeting: Poster 40. Presented October 17, 2008.
October 20, 2008 (Baltimore, Maryland) — The results of a new study analyzing the specific expression profiles of micro (mi)RNA in different categories of renal cancer indicate that the expression profiles are unique and different from one another.
The next goal is to use these results to look at potential therapeutic targets. "Once we are able to understand the expression profiles better for specific tumors — not just renal cancers, but all cancers — and identify how they actually affect gene regulation, that can help direct therapies," lead author Gary Tozbikian, MD, a second-year resident in the department of pathology at the University of Pennsylvania, in Philadelphia, said in an interview with Medscape Pathology.
"MiRNAs are unique molecules," said Dr. Tozbikian. "They are very short segments of RNA that do not actually encode for anything, but play a profound role in regulating gene expression, and they get perturbed in cancer."
"It is known that these miRNA molecules act as master switches, controlling gene expression, determining how tissues will behave," added Dr. Tozbikian. It is thought that by studying these molecules, scientists can understand more about tumor biology and find clues to outcomes for cancer patients.
"This is the first study of its kind," noted Dr. Tozbikian. The study focused specifically on renal cell carcinoma (RCC). However, a number of studies that have looked at these types of data in other cancers, including colon, breast, and lung, have found unique expression profiles for those tumors. "Some of those studies have even shown that the expression profiles have prognostic information, indicating, for example, that if certain miRNAs are upregulated, patients' outcomes are worse or they do not respond to chemotherapy," explained Dr. Tozbikian
The researchers have identified the unique miRNA profiles of chromophobe (CHRCC), papillary (PRCC), and clear cell carcinoma (CCRCC). They studied 25 cases of CHRCC, PRCC, and CCRCC. RNA was extracted from tumor and normal kidney-tissue samples that were formalin-fixed and paraffin-embedded.
The RNA was hybridized to a "very comprehensive 754 miRNA probes and wells microarray," noted Joel Shilling, MD, medical director of Quest Diagnostics, in Portland, Oregon, who commented on the study results in an interview with Medscape Pathology. "This is cutting-edge," added Dr. Shilling, who was not involved in the study.
Dr. Tozbikian and colleagues calculated a 1-way analysis of variance across all 3 groups. Only miRNAs with a change 3-fold or more with respect to normal kidney tissue were considered for the analysis, explained Dr. Tozbikian in his poster presentation. CCRCC was compared with PRCC, and CCRCC was compared with CHRCC, and the miRNAs were prioritized by degree of change and P value.
The study results showed that 7 miRNAs were upregulated more than 3-fold in CCRCC, whereas 20 were downregulated. In PRCC, 9 miRNAs were upregulated and 2 were downregulated. In CHRCC, 20 miRNAs were upregulated, with more than a 10-fold expression, and 3 were downregulated. A total of 9 miRNAs were differentially expressed between CHRCC and PRCC. The investigators confirmed the results by reverse-transcriptase polymerase chain reaction, using 6 probes for miRNA.
"We were successful in showing that a distinct subset of miRNAs is differentially expressed between the 3 categories of RCC tumors studied," concluded Dr. Tozbikian, adding that the data provide a strong rationale for further cohort studies "to evaluate the diagnostic utility of miRNAs in the classification of renal cell carcinoma."
"We face this problem in routine interpretation of biopsies, and here is a parameter that we can measure that would help the pathologist confirm the diagnosis," noted Dr. Shilling: "It will be a while until these results, if confirmed, willactually be in the pathology laboratory, but many of these novel microarrays are now coming down to the community hospital and pathology branch laboratory setting."
The study did not receive commercial support. Dr. Tozbikian and Dr. Shilling have disclosed no relevant financial relationships.
American Society for Clinical Pathology (ASCP) 2008 Annual Meeting: Poster 40. Presented October 17, 2008.
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