A Noninvasive Prediction Nomogram for Lymph Node Metastasis of Hepatocellular Carcinoma Based on Serum Long Noncoding RNAs.

BACKGROUND AND OBJECTIVES: Lymph node metastasis (LNM) is common in hepatocellular carcinoma (HCC). In order to intervene HCC LNM in advance, we developed a prediction nomogram based on serum long noncoding RNA (lncRNA). METHODS: Serum samples from 242 HCC patients were gathered and randomly enrolled into the training and validation cohorts. LncRNAs screened out from microarray were quantified with qRT-PCR. Univariate and multivariate analyses were applied for screening independent risk factors. A prediction nomogram was ultimately developed for HCC LNM. The nomogram was estimated by discrimination and calibration tests in the validation cohort. The effects of the candidate lncRNA on the malignant phenotypes of HCC cells were further explored by wound healing assay and colony formation assay. RESULTS: ENST00000418803, lnc-ZNF35-4:1, lnc-EPS15L1-2:1, BCLC stage, and vascular invasion were selected as components of the nomogram according to the adjusted multivariate analysis. The nomogram effectively predicted the HCC LNM risk among the cohorts with suitable calibration fittings and displayed high discrimination with C-index of 0.89 and 0.85. Moreover, the abnormally high expression of lnc-EPS15L1-2:1 in HCC cell lines showed significant carcinogenic effects. CONCLUSIONS: The noninvasive nomogram may provide more diagnostic basis for treatments of HCC. The biomarkers identified can bring new clues to basic researches.

IL-33/ST2 pathway contributes to metastasis of human colorectal cancer.

Interleukin-33 (IL-33) was recently implicated in cancer pathogenesis. However, the possible effect of IL-33 on tumor progression of colorectal cancer (CRC), which is one of the most commonly diagnosed and lethal cancers worldwide, was still unclear. Here we evaluated the potential role of IL-33/ST2 pathway in metastasis of human CRC. We found an elevated expression of IL-33 and ST2 in tumor tissues of CRC patients. Higher expressions of IL-33 and ST2 were observed in poor-differentiated human CRC cells. Of note, IL-33 stimulation promoted the invasion of human CRC cells in a dose dependent manner. Enhanced IL-33/ST2 signaling promoted CRC metastasis, while attenuated IL-33/ST2 signaling decreased CRC metastasis. In consistent, enforced IL-33 expression in human CRC cells enhanced their growth, metastasis and reduced the survival time in nude mice, while decreased IL-33 expression in human CRC cells inhibited their growth, metastasis and prolonged the survival time in nude mice. Finally, we observed an increased expression of IL-6, CXCR4, MMP2 and MMP9 in response to IL-33/ST2 signaling in human CRC cells, which were crucial for the enhanced metastasis by IL-33 stimulation. Collectively, our findings demonstrated that IL-33/ST2 pathway could contribute to the metastasis of human CRC, which could enlarge the understanding of CRC pathogenesis and provide clues for developing new CRC therapeutics.