Abstract
Expression of HOX transcript antisense intergenic RNA (HOTAIR), a large intergenic noncoding RNA (lincRNA), has been described as a metastases-associated lincRNA in various cancers including breast, liver and colon cancer cancers. We sought to determine if expression of HOTAIR could be used as a surrogate for assessing nodal metastases and evaluated RNA in situ hybridization (RNA-ISH) assay in a tissue microarray constructed from 133 breast cancer patients. The prognostic value of HOTAIR was further validated in large cohorts using The Cancer Genome Atlas (TCGA) breast cancer subjects. RNA-ISH analysis was successful in 94 cases (17% cases scored 0, 32.9% scored 1, 30.8% scored 2, and 19.1% scored 3). The expression of HOTAIR did not correlate with nodal metastasis regardless of the scoring intensity or with other study parameters (age, tumor size and grade, expression status). Further analysis of TCGA dataset showed that HOTAIR expression was lower in ductal carcinomas but higher in ER-negative tumors. Overexpression of HOTAIR was not associated with nodal metastases or prognosis in ER-positive patients. Its function as a poor prognostic indicator in ER-negative patients was restricted to node-positive patients. HOTAIR appears to be a marker for lymphatic metastases rather than hematogenous metastases in ER-negative patients.
Highlights
Expression of HOX transcript antisense intergenic RNA (HOTAIR), a large intergenic noncoding RNA, has been described as a metastases-associated lincRNA in various cancers including breast, liver and colon cancer cancers
We sought to determine if expression of HOTAIR could be used as a surrogate for assessing nodal metastases and evaluated RNA in situ hybridization (RNA-ISH) assay in a tissue microarray constructed from 133 breast cancer patients
The expression of HOTAIR did not correlate with nodal metastasis regardless of the scoring intensity used as a cutoff point (Table 1)
Summary
Expression of HOX transcript antisense intergenic RNA (HOTAIR), a large intergenic noncoding RNA (lincRNA), has been described as a metastases-associated lincRNA in various cancers including breast, liver and colon cancer cancers. Gupta et al hybridized RNA from normal breast epithelia, primary tumors, and distant metastases to ultrahigh density HOX tiling array[17]. They found 170 ncRNAs and 63 HOX exons that were differentially expressed. HOTAIR (HOX antisense intergenic RNA) was one of the metastases associated lincRNAs. Rinn et al and Woo and Kingston et al had previously identified its role in regulating HOX genes[18,19]. The expression was a significant predictor of metastases and death in a series of 132 breast cancer patients with extensive followup
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