De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer

Xiwei Wu, George Somlo, Yang Yu, Melanie R. Palomares, Arthur X. Li, Weiying Zhou, Amy Chow, Yun Yen, John J. Rossi, Harry Gao, Jinhui Wang, Yate Ching Yuan, Paul Frankel, Sierra Li, Kimlin T. Ashing-Giwa, Guihua Sun, Yafan Wang, Robin Smith, Kim Robinson, Xiubao Ren & 1 others Shizhen E. Wang

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Background: MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome.Methods: The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers.Results: More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients.Conclusions: Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.

Original languageEnglish
Article number42
JournalJournal of Translational Medicine
Volume10
Issue number1
DOIs
Publication statusPublished - Mar 8 2012
Externally publishedYes

Fingerprint

MicroRNAs
Biomarkers
Breast Neoplasms
Chemotherapy
Inflammatory Breast Neoplasms
Drug Therapy
High-Throughput Nucleotide Sequencing
RNA
Blood
Neoplasm Metastasis
Recurrence
Tumors
Neoplasms
Association reactions
Polymerase Chain Reaction
Therapeutics
Serum

Keywords

  • Biomarker
  • Breast cancer
  • Metastasis
  • Mirna
  • Neoadjuvant chemotherapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer. / Wu, Xiwei; Somlo, George; Yu, Yang; Palomares, Melanie R.; Li, Arthur X.; Zhou, Weiying; Chow, Amy; Yen, Yun; Rossi, John J.; Gao, Harry; Wang, Jinhui; Yuan, Yate Ching; Frankel, Paul; Li, Sierra; Ashing-Giwa, Kimlin T.; Sun, Guihua; Wang, Yafan; Smith, Robin; Robinson, Kim; Ren, Xiubao; Wang, Shizhen E.

In: Journal of Translational Medicine, Vol. 10, No. 1, 42, 08.03.2012.

Research output: Contribution to journalArticle

Wu, X, Somlo, G, Yu, Y, Palomares, MR, Li, AX, Zhou, W, Chow, A, Yen, Y, Rossi, JJ, Gao, H, Wang, J, Yuan, YC, Frankel, P, Li, S, Ashing-Giwa, KT, Sun, G, Wang, Y, Smith, R, Robinson, K, Ren, X & Wang, SE 2012, 'De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer', Journal of Translational Medicine, vol. 10, no. 1, 42. https://doi.org/10.1186/1479-5876-10-42
Wu, Xiwei ; Somlo, George ; Yu, Yang ; Palomares, Melanie R. ; Li, Arthur X. ; Zhou, Weiying ; Chow, Amy ; Yen, Yun ; Rossi, John J. ; Gao, Harry ; Wang, Jinhui ; Yuan, Yate Ching ; Frankel, Paul ; Li, Sierra ; Ashing-Giwa, Kimlin T. ; Sun, Guihua ; Wang, Yafan ; Smith, Robin ; Robinson, Kim ; Ren, Xiubao ; Wang, Shizhen E. / De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer. In: Journal of Translational Medicine. 2012 ; Vol. 10, No. 1.
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abstract = "Background: MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome.Methods: The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers.Results: More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients.Conclusions: Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.",
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AU - Somlo, George

AU - Yu, Yang

AU - Palomares, Melanie R.

AU - Li, Arthur X.

AU - Zhou, Weiying

AU - Chow, Amy

AU - Yen, Yun

AU - Rossi, John J.

AU - Gao, Harry

AU - Wang, Jinhui

AU - Yuan, Yate Ching

AU - Frankel, Paul

AU - Li, Sierra

AU - Ashing-Giwa, Kimlin T.

AU - Sun, Guihua

AU - Wang, Yafan

AU - Smith, Robin

AU - Robinson, Kim

AU - Ren, Xiubao

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N2 - Background: MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome.Methods: The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers.Results: More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients.Conclusions: Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.

AB - Background: MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome.Methods: The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers.Results: More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients.Conclusions: Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.

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KW - Neoadjuvant chemotherapy

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