Relative expression of several lncRNAs deregulated in LIHC in cell lines and liver tumors. A. Expression in cancer cells and fibroblasts. RNA was isolated from the indicated cells and the expression of the indicated lncRNAs was quantified by qRT-PCR. As a reference, the average expression of each lncRNA in all the liver cells evaluated is indicated as "average". The levels of RPLP0 mRNA were also evaluated and used as a reference to calculate the relative expression. The values indicate the average of 3 different experiments. Error bars denote standard deviations. A relative expression of 0.01 marks the lower detection limit. B. Expression in LIHC. The relative expression of each lncRNA was evaluated in paired peritumoral (PT) and tumor (T) samples from the TCGA RNA-Seq data. The result of the statistical analysis with paired t-tests is indicated in each graph. C. Analysis of RP11-242J7.1 expression in patients with different prognosis. Relative expression of RP11-242J7.1 in tumor and peritumoral samples of patients from the BCL-CUN cohort with best prognosis (Best; left) and worse prognosis (Worse, right). The result of the statistical analysis with Wilcoxon matched pairs signed rank tests is indicated in each graph. D. Analysis of lncRNAs associated with tumor differentiation (well versus poorly differentiated), tumor size (small versus large tumors) and with the number of tumor nodules (one versus multiple nodules) using data from the BCL-CUN cohort. The result of the statistical analysis (two-tailed unpaired t-test in B and U-Mann Whitney in C) is indicated in each graph.
ARTICLE ABSTRACT
The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets allow unprecedented gene expression analyses. Here, using these datasets, we performed pan-cancer and pan-tissue identification of coding and long noncoding RNA (lncRNA) transcripts differentially expressed in tumors and preferentially expressed in healthy tissues and/or tumors. Pan-cancer comparison of mRNAs and lncRNAs showed that lncRNAs were deregulated in a more tumor-specific manner. Given that lncRNAs are more tissue-specific than mRNAs, we identified healthy tissues that preferentially express lncRNAs upregulated in tumors and found that testis, brain, the digestive tract, and blood/spleen were the most prevalent. In addition, specific tumors also upregulate lncRNAs preferentially expressed in other tissues, generating a unique signature for each tumor type. Most tumors studied downregulated lncRNAs preferentially expressed in their tissue of origin, probably as a result of dedifferentiation. However, the same lncRNAs could be upregulated in other tumors, resulting in "bimorphic" transcripts. In hepatocellular carcinoma (HCC), the upregulated genes identified were expressed at higher levels in patients with worse prognosis. Some lncRNAs upregulated in HCC and preferentially expressed in healthy testis or brain were predicted to function as oncogenes and were significantly associated with higher tumor burden, and poor prognosis, suggesting their relevance in hepatocarcinogenesis and/or tumor evolution. Taken together, therapies targeting oncogenic lncRNAs should take into consideration the healthy tissue, where the lncRNAs are preferentially expressed, to predict and decrease unwanted secondary effects and increase potency.
Comprehensive analysis of coding and noncoding genes expressed in different tumors and normal tissues, which should be taken into account to predict side effects from potential coding and noncoding gene-targeting therapies.
