Breast Cancer: Radiogenomic Biomarker Reveals Associations among Dynamic Contrast-enhanced MR Imaging, Long Noncoding RNA, and Metastasis.
OBJECTIVE
To perform a radiogenomic analysis of women with breast cancer to study the multiscale relationships among quantitative computer vision-extracted dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging phenotypes, early metastasis, and long noncoding RNA (lncRNA) expression determined by means of high-resolution next-generation RNA sequencing.


METHODS
In this institutional review board-approved study, an automated image analysis platform extracted 47 computational quantitative features from DCE MR imaging data in a training set (n = 19) to screen for MR imaging biomarkers indicative of poor metastasis-free survival (MFS). The lncRNA molecular landscape of the candidate feature was defined by using an RNA sequencing-specific negative binomial distribution differential expression analysis. Then, this radiogenomic biomarker was applied prospectively to a validation set (n = 42) to allow prediction of MFS and lncRNA expression by using quantitative polymerase chain reaction analysis.


RESULTS
The quantitative MR imaging feature, enhancing rim fraction score, was predictive of MFS in the training set (P = .007). RNA sequencing analysis yielded an average of 55.7 × 10(6) reads per sample and identified 14 880 lncRNAs from a background of 189 883 transcripts per sample. Radiogenomic analysis allowed identification of three previously uncharacterized and five named lncRNAs significantly associated with high enhancing rim fraction, including Homeobox transcript antisense intergenic RNA (HOTAIR) (P < .05), a known predictor of poor MFS in patients with breast cancer. Independent validation confirmed the association of the enhancing rim fraction phenotype with both MFS (P = .002) and expression of four of the top five differentially expressed lncRNAs (P < .05), including HOTAIR.


CONCLUSIONS
The enhancing rim fraction score, a quantitative DCE MR imaging lncRNA radiogenomic biomarker, is associated with early metastasis and expression of the known predictor of metastatic progression, HOTAIR.
From the Department of Radiological Sciences, UCLA School of Medicine, Box 951721, CHS 17-135, Los Angeles, CA 90095-1721 (S.Y., L.D., N.J., D.H., M.D.K.); and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea (W.H., Y.K., J.H.K.).
Shota
S
Yamamoto
Wonshik
W
Han
Youngwoo
Y
Kim
Liutao
L
Du
Neema
N
Jamshidi
Danshan
D
Huang
Jong Hyo
JH
Kim
Michael D
MD
Kuo
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D003287:Contrast Media; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000032:analysis / Q000096:biosynthesis; D012189:Retrospective Studies; D017423:Sequence Analysis, RNA
D014408:Biomarkers, Tumor; D003287:Contrast Media; D062085:RNA, Long Noncoding