MiR-486-5p Downregulation Marks an Early Event in Colorectal Carcinogenesis

Katherine A. Kelley, Nicole Wieghard, Yuki Chin, Amiee Potter, Motomi (Tomi) Mori, Melissa Wong, Kwang-Yung Chin, Vassiliki Tsikitis

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

OBJECTIVE: The purpose of this study was to identify a microRNA signature associated with the primary tumor and metastatic site in stage IV disease and to examine whether the signature is evident in earlier stages.

DESIGN: A microRNA profile was generated and then explored in normal colon tissue (n = 5), early stage (stage I and II; n = 10), and late-stage (stage III and IV; n = 14) colorectal primary tumors via polymerase chain reaction to delineate molecular events that may promote colorectal carcinogenesis.

SETTING: Genome-wide microRNA expression profiling was performed.

PATIENTS: A total of 14 patient-matched stage IV primary colorectal cancer tumors and corresponding liver metastases were included.

MAIN OUTCOME MEASURES: MicroRNA array technology was used to identify microRNA expression-predictive metastatic potential in the primary tumor.

RESULTS: A distinct 9-member signature group of microRNAs was concurrent in stage IV primary colorectal cancer and their corresponding liver metastases, when compared with surrounding unaffected colon and liver tissue (microRNA-18b, microRNA-93, microRNA-182, microRNA-183, microRNA21, microRNA-486-5p, microRNA-500a, microRNA-552, and microRNA-941). Of the microRNA panel, only microRNA486-5p was differentially expressed in early stage colorectal cancer samples compared with normal tissue (p = 0.001) and additionally differentially expressed between late-stage colorectal cancer samples and normal tissue (p < 0.01).

LIMITATIONS: Our microRNA profile was generated in a small subset of patients and will require validation in more samples.

CONCLUSIONS: We identified a distinct microRNA signature in primary colon and matched metastatic disease. On additional investigation, 1 microRNA was differentially expressed in both early and late-stage cancer patient samples, and it may herald an early event in colorectal carcinogenesis. This study warrants additional investigation with a larger patient cohort to better understand the effect of microRNAs in carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A723.

BACKGROUND: MicroRNAs are dysregulated in colorectal cancer and subsets correlated with advanced tumor stage and metastasis. Data are lacking on microRNA dysregulation from early to late-stage disease.

Original languageEnglish (US)
Pages (from-to)1290-1296
Number of pages7
JournalDiseases of the Colon and Rectum
Volume61
Issue number11
DOIs
StatePublished - Nov 1 2018

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MicroRNAs
Carcinogenesis
Down-Regulation
Colorectal Neoplasms
Colon
Neoplasm Metastasis
Liver
Neoplasms

ASJC Scopus subject areas

  • Gastroenterology

Cite this

MiR-486-5p Downregulation Marks an Early Event in Colorectal Carcinogenesis. / Kelley, Katherine A.; Wieghard, Nicole; Chin, Yuki; Potter, Amiee; Mori, Motomi (Tomi); Wong, Melissa; Chin, Kwang-Yung; Tsikitis, Vassiliki.

In: Diseases of the Colon and Rectum, Vol. 61, No. 11, 01.11.2018, p. 1290-1296.

Research output: Contribution to journalArticle

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abstract = "OBJECTIVE: The purpose of this study was to identify a microRNA signature associated with the primary tumor and metastatic site in stage IV disease and to examine whether the signature is evident in earlier stages.DESIGN: A microRNA profile was generated and then explored in normal colon tissue (n = 5), early stage (stage I and II; n = 10), and late-stage (stage III and IV; n = 14) colorectal primary tumors via polymerase chain reaction to delineate molecular events that may promote colorectal carcinogenesis.SETTING: Genome-wide microRNA expression profiling was performed.PATIENTS: A total of 14 patient-matched stage IV primary colorectal cancer tumors and corresponding liver metastases were included.MAIN OUTCOME MEASURES: MicroRNA array technology was used to identify microRNA expression-predictive metastatic potential in the primary tumor.RESULTS: A distinct 9-member signature group of microRNAs was concurrent in stage IV primary colorectal cancer and their corresponding liver metastases, when compared with surrounding unaffected colon and liver tissue (microRNA-18b, microRNA-93, microRNA-182, microRNA-183, microRNA21, microRNA-486-5p, microRNA-500a, microRNA-552, and microRNA-941). Of the microRNA panel, only microRNA486-5p was differentially expressed in early stage colorectal cancer samples compared with normal tissue (p = 0.001) and additionally differentially expressed between late-stage colorectal cancer samples and normal tissue (p < 0.01).LIMITATIONS: Our microRNA profile was generated in a small subset of patients and will require validation in more samples.CONCLUSIONS: We identified a distinct microRNA signature in primary colon and matched metastatic disease. On additional investigation, 1 microRNA was differentially expressed in both early and late-stage cancer patient samples, and it may herald an early event in colorectal carcinogenesis. This study warrants additional investigation with a larger patient cohort to better understand the effect of microRNAs in carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A723.BACKGROUND: MicroRNAs are dysregulated in colorectal cancer and subsets correlated with advanced tumor stage and metastasis. Data are lacking on microRNA dysregulation from early to late-stage disease.",
author = "Kelley, {Katherine A.} and Nicole Wieghard and Yuki Chin and Amiee Potter and Mori, {Motomi (Tomi)} and Melissa Wong and Kwang-Yung Chin and Vassiliki Tsikitis",
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AU - Kelley, Katherine A.

AU - Wieghard, Nicole

AU - Chin, Yuki

AU - Potter, Amiee

AU - Mori, Motomi (Tomi)

AU - Wong, Melissa

AU - Chin, Kwang-Yung

AU - Tsikitis, Vassiliki

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N2 - OBJECTIVE: The purpose of this study was to identify a microRNA signature associated with the primary tumor and metastatic site in stage IV disease and to examine whether the signature is evident in earlier stages.DESIGN: A microRNA profile was generated and then explored in normal colon tissue (n = 5), early stage (stage I and II; n = 10), and late-stage (stage III and IV; n = 14) colorectal primary tumors via polymerase chain reaction to delineate molecular events that may promote colorectal carcinogenesis.SETTING: Genome-wide microRNA expression profiling was performed.PATIENTS: A total of 14 patient-matched stage IV primary colorectal cancer tumors and corresponding liver metastases were included.MAIN OUTCOME MEASURES: MicroRNA array technology was used to identify microRNA expression-predictive metastatic potential in the primary tumor.RESULTS: A distinct 9-member signature group of microRNAs was concurrent in stage IV primary colorectal cancer and their corresponding liver metastases, when compared with surrounding unaffected colon and liver tissue (microRNA-18b, microRNA-93, microRNA-182, microRNA-183, microRNA21, microRNA-486-5p, microRNA-500a, microRNA-552, and microRNA-941). Of the microRNA panel, only microRNA486-5p was differentially expressed in early stage colorectal cancer samples compared with normal tissue (p = 0.001) and additionally differentially expressed between late-stage colorectal cancer samples and normal tissue (p < 0.01).LIMITATIONS: Our microRNA profile was generated in a small subset of patients and will require validation in more samples.CONCLUSIONS: We identified a distinct microRNA signature in primary colon and matched metastatic disease. On additional investigation, 1 microRNA was differentially expressed in both early and late-stage cancer patient samples, and it may herald an early event in colorectal carcinogenesis. This study warrants additional investigation with a larger patient cohort to better understand the effect of microRNAs in carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A723.BACKGROUND: MicroRNAs are dysregulated in colorectal cancer and subsets correlated with advanced tumor stage and metastasis. Data are lacking on microRNA dysregulation from early to late-stage disease.

AB - OBJECTIVE: The purpose of this study was to identify a microRNA signature associated with the primary tumor and metastatic site in stage IV disease and to examine whether the signature is evident in earlier stages.DESIGN: A microRNA profile was generated and then explored in normal colon tissue (n = 5), early stage (stage I and II; n = 10), and late-stage (stage III and IV; n = 14) colorectal primary tumors via polymerase chain reaction to delineate molecular events that may promote colorectal carcinogenesis.SETTING: Genome-wide microRNA expression profiling was performed.PATIENTS: A total of 14 patient-matched stage IV primary colorectal cancer tumors and corresponding liver metastases were included.MAIN OUTCOME MEASURES: MicroRNA array technology was used to identify microRNA expression-predictive metastatic potential in the primary tumor.RESULTS: A distinct 9-member signature group of microRNAs was concurrent in stage IV primary colorectal cancer and their corresponding liver metastases, when compared with surrounding unaffected colon and liver tissue (microRNA-18b, microRNA-93, microRNA-182, microRNA-183, microRNA21, microRNA-486-5p, microRNA-500a, microRNA-552, and microRNA-941). Of the microRNA panel, only microRNA486-5p was differentially expressed in early stage colorectal cancer samples compared with normal tissue (p = 0.001) and additionally differentially expressed between late-stage colorectal cancer samples and normal tissue (p < 0.01).LIMITATIONS: Our microRNA profile was generated in a small subset of patients and will require validation in more samples.CONCLUSIONS: We identified a distinct microRNA signature in primary colon and matched metastatic disease. On additional investigation, 1 microRNA was differentially expressed in both early and late-stage cancer patient samples, and it may herald an early event in colorectal carcinogenesis. This study warrants additional investigation with a larger patient cohort to better understand the effect of microRNAs in carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A723.BACKGROUND: MicroRNAs are dysregulated in colorectal cancer and subsets correlated with advanced tumor stage and metastasis. Data are lacking on microRNA dysregulation from early to late-stage disease.

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