HOTAIR long non-coding RNA is a negative prognostic factor not only in primary tumors, but also in the blood of colorectal cancer patients

Abstract

Colorectal cancer (CRC) is one of the main causes of death of neoplasia. Demand for predictive and prognostic markers to reverse this trend is increasing. Long non-coding RNA HOTAIR (Homeobox Transcript Antisense Intergenic RNA) overexpression in tumors was previously associated with poor prognosis and higher mortality in different carcinomas. We analyzed HOTAIR expression levels in tumor and blood of incident sporadic CRC patients in relation to their overall survival with the aim to evaluate surrogate prognostic marker for CRC. Tissue donor group consisted of 73 CRC patients sampled for tumor and normal tissue. Blood donor group was represented by 84 CRC patients compared with 40 healthy controls. Patients were characterized for tumor-node-metastasis stage, tumor grade, microsatellite instability and tumor penetration by stromal cells. HOTAIR levels were assessed by real-time quantitative PCR. CRC patients had higher HOTAIR expression in blood than healthy controls (P = 0.0001), whereas there was no difference in HOTAIR levels between tumor and adjacent mucosa of CRC patients. HOTAIR levels positively correlated between blood and tumor (R = 0.43, P = 0.03). High HOTAIR levels in tumors were associated with higher mortality of patients [Cox's proportional hazard, hazard ratio = 4.4, 95% confidence interval: 1.0-19.2, P = 0.046]. The hazard ratio was even higher when blood HOTAIR levels were taken into account (hazard ratio = 5.9, 95% confidence interval: 1.3-26.1, P = 0.019). Upregulated HOTAIR relative expression in primary tumors and in blood of CRC patients is associated with unfavorable prognosis. Our data suggest that HOTAIR blood levels may serve as potential surrogate prognostic marker in sporadic CRC.

Dysregulation of long non-coding RNA profiles in human colorectal cancer and its association with overall survival

“…In the present study, HOTTIP was detected to exhibit dysregulation in CRC cancer tissues (E-GEOD-31737). Additionally, the variance transcripts of HOTAIR, including HOTAIRM1, were determined to exhibit differential levels in CRC cancer tissues (E-GEOD-31737 and E-MATB-829) (8). However, variances associated with measurement error were not comparable across different studies (26).…”

“…For instance, colorectal cancer associated transcript 2 was identified by Ling et al as a lncRNA mapping to 8q24 that promoted metastatic progression in CRC (7). Another lncRNA, homeobox transcript antisense intergenic RNA (HOTAIR) has been determined to exhibit higher levels in the plasma of CRC patients than in healthy controls, and its overexpression predicted unfavorable prognosis (8). The association between prognosis of CRC patients and expression of prostate cancer associated transcript 1 and metastasis associated lung adenocarcinoma transcript 1 has also been explored (9,10).…”

Overexpression of long non‑coding RNA colon cancer‑associated transcript 2 is associated with advanced tumor progression and poor prognosis in patients with colorectal cancer

“…Upregulated lncRNA HOTAIR relative expression in primary tumors and in the blood of patients with CRC is associated with unfavorable prognosis (13). lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been shown to be upregulated in clinical CRC tissue samples (14).…”

Expression and clinicopathological significance of the lncRNA HOXA11-AS in colorectal cancer

“…Previous studies have indicated that the abnormal expression of certain well-defined lncRNAs, including HOX transcript antisense RNA, maternally expressed 3 and metastasis associated lung adenocarcinoma transcript 1, are strongly correlated with CRC development and progression (23)(24)(25). Therefore, the role of lncRNAs in the development and progression of CRC is gaining increasing attention (26).…”