IDDF2019-ABS-0314 RNA-sequencing identify C1/C2 molecular classification and a novel lncRNA of duodenum adenocarcinoma

Background Duodenum adenocarcinoma is one of the most common small intestinal malignancies, accounting for approximately 50% of small intestinal malignancies. Molecular classification and lncRNA expression profile of duodenum adenocarcinoma were unknown. Methods RNA-seqeuncing of 11 pairs of duodenal adenocarcinoma tissues and adjacent normal tissues was carried out. Biological information analysis and RT-PCR were further carried out. We performed signal pathways enrichment and cluster analysis. We established C1/C2 molecular classification, explored its prognostic value. LncRNA expression profile of duodenum adenocarcinoma was also explored. Function and the RNA-binding protein of the lncRNA were confirmed. Results Cancer hallmark signal pathways enrichment found that the MYC, mTORC1, Notch and G2M signal pathways were significantly enriched. KEGG signal pathways enrichment showed that ribosomal production, IL-17 and P53 signal pathways were significantly enriched. Cluster analysis showed that patients can be divided into two molecular subtypes, C1 and C2 subtypes. In C1 patients, base repair signal pathway was significantly enriched, while in C2 patients, PI3K-AKT, RAS and Hippo signal pathway were significantly enriched. Gastric cancer and colorectal cancer patients could also be automatically divided into C1 and C2 subtypes. C1 and C2 molecular subtypes have prognostic value in predicting the overall survival of 11 duodenum adenocarcinoma patients, gastric cancer and colorectal cancer patients in TCGA database, the prognosis of C2 subtype patients was worse. Tumor mutation burden (TMB) of C2 subtype was significantly lower than that of C1 subtype, Cancer Associated Fibroblast(CAF) cells of C2 subtype were significantly increased, and Myeloid-derived suppressor cells(MDSC) were significantly decreased. Analysis of the expression profile of lncRNAs showed that linc01559 increased most significantly in cancer tissues. We conducted siRNA interference on linc01559 in WDC-1 and Hutu-80 cells. Cell proliferation, invasion and migration were significantly decreased. Apoptosis rate was significantly increased, suggesting that linc01559 can promote proliferation and metastasis of duodenum adenocarcinoma. RNA pulldown and RIP confirmed that the RNA-binding protein of linc01559 is GRSF1(figures 1,2,3, and 4). Conclusions C1 and C2 molecular subtypes were prognostic of overall survival of duodenum adenocarcinoma. Linc01559 is a novel and important lncRNA that can promote the proliferation and metastasis of duodenum adenocarcinoma.