S. J. O’Brien1, C. Fiechter1, M. Paas1, A. Rochet1, S. Galandiuk1 1University Of Louisville,Price Institute Of Surgical Research, The Hiram C. Polk Jr. M.D. Department Of Surgery,Louisville, KY, USA
Introduction:
Colorectal adenocarcinoma is the fourth leading cause of cancer-related death in the United States. Non-coding RNAs have recently been identified as critical mediators of tumor biology. Long non-coding RNAs (lncRNAs) are diverse in their mechanisms but are known mediators of tumor progression; H19 is a well characterized lncRNA involved in the regulation of P53 and in cancer progression. The aim of this study was to identify the association of tumor H19 expression with recurrence-free and overall survival in a colon cancer data set.
Methods:
The clinical dataset from The Cancer Genome Atlas colon adenocarcinoma data set was downloaded using FirebrowseR. The normalized expression of H19 from the associated RNA-seq data set was downloaded using cBioportal. Univariable and multivariable cox proportional regression analysis were used to identify an association between H19 expression in cancer tissue at the time of resection and recurrence-free, and overall survival.
Results:
Four hundred and eighteen patients were included in this study. Median age was 69 years (IQR 58-75) Two hundred and nineteen patients (52%) were men. Most tumors were located in the sigmoid colon (135/418- 32%). Two hundred and thirty-nine patients (57%) had stage 1 or 2 cancers. Lymphatic invasion was present in 36% patients (152/418). The median expression of H19 in the data set defined high or low expression groups. The only difference between groups was that high H19 expression was associated with stage 3 and 4 disease (p=0.048). There was no difference in the overall survival between the low and high H19 groups (Log Rank=0.481). High H19 expression was associated with reduced recurrence-free survival (Log-Rank=0.007) (Figure 1). On univariable regression analysis, high H19 expression, stage 3 or 4 disease, and lymphatic invasion were associated with disease recurrence (Hazard ratio=1.861, 95%CI:1.181-2.932, p=0.007, HR=2.498, 95%CI: 1.622-3.847, P<0.001, and HR= 1.928, 95%CI: 1.233-3.014, p=0.004 respectively). On multivariable regression analysis, only high H19 expression (HR=1.686, 95%CI: 1.046-2.720, p=0.032) and stage 3 or 4 disease (HR=2.888, 95%CI: 1.317-3.976, P=0.003) remained statistically significant predictors of disease recurrence.
Conclusion:
H19 was associated with advanced stage of tumor disease and is a significant predictor of recurrent cancer on multivariable analysis. The results of this study are in keeping with in vitro studies in that H19 has a number of oncogenic mechanisms of action, including increased proliferation and mediation of epithelial-mesenchymal transition. As it is a critical molecule in cell regulation, it may have both prognostic and therapeutic uses in the future.
