Genes associated with bowel metastases in ovarian cancer
GYNECOLOGIC ONCOLOGY
Authors: Mariani, Andrea; Wang, Chen; Oberg, Ann L.; Riska, Shaun M.; Torres, Michelle; Kumka, Joseph; Multinu, Francesco; Sagar, Gunisha; Roy, Debarshi; Jung, Deok-Beom; Zhang, Qing; Grassi, Tommaso; Visscher, Daniel W.; Patel, Vatsal P.; Jin, Ling; Staub, Julie K.; Cliby, William A.; Weroha, Saravut J.; Kalli, Kimberly R.; Hartmann, Lynn C.; Kaufmann, Scott H.; Goode, Ellen L.; Shridhar, Viji
Abstract
Objective. This study is designed to identify genes and pathways that could promote metastasis to the bowel in high-grade serous ovarian cancer (OC) and evaluate their associations with clinical outcomes. Methods. We performed RNA sequencing of OC primary tumors (PTs) and their corresponding bowel metastases (n = 21 discovery set; n = 18 replication set). Differentially expressed genes (DEGs) were those expressed at least 2-fold higher in bowel metastases (BMets) than PTs in at least 30% of patients (P < .05) with no increased expression in paired benign bowel tissue and were validated with quantitative reverse transcription PCR. Using an independent OC cohort (n = 333), associations between DEGs in PTs and surgical and clinical outcomes were performed. Immunohistochemistry and mouse xenograft studies were performed to confirm the role of LRRC15 in promoting metastasis. Results. Among 27 DEGs in the discovery set, 21 were confirmed in the replication set: SFRP2, Col11A1, LRRC15, ADAM12, ADAMTS12, MFAP5, LUM, PLPP4, FAP, POSTN, GRP, MMP11, MMP13, C1QTNF3, EPYC, DIO2, KCNA1, NETO1, NTM, MYH13, and PVALB. Higher expression of more than half of the genes in the PT was associated with an increased requirement for bowel resection at primary surgery and an inability to achieve complete cytoreduction. Increased expression of LRRC15 in BMets was confirmed by immunohistochemistry and knockdown of LRRC15 significantly inhibited tumor progression in mice. Conclusions. We identified 21 genes that are overexpressed in bowel metastases among patients with OC. Our findings will help select potential molecular targets for the prevention and treatment of malignant bowel obstruction in OC. Published by Elsevier Inc.
Transcriptome Analysis of Adipose Tissue Indicates That the cAMP Signaling Pathway Affects the Feed Efficiency of Pigs
GENES
Authors: Xu, Yueyuan; Qi, Xiaolong; Hu, Mingyang; Lin, Ruiyi; Hou, Ye; Wang, Zhangxu; Zhou, Huanhuan; Zhao, Yunxia; Luan, Yu; Zhao, Shuhong; Li, Xinyun
Abstract
Feed efficiency (FE) is one of the main factors that determine the production costs in the pig industry. In this study, RNA Sequencing (RNA-seq) was applied to identify genes and long intergenic non-coding RNAs (lincRNAs) that are differentially expressed (DE) in the adipose tissues of Yorkshire pigs with extremely high and low FE. In total, 147 annotated genes and 18 lincRNAs were identified as DE between high-and low-FE pigs. Seventeen DE lincRNAs were significantly correlated with 112 DE annotated genes at the transcriptional level. Gene ontology (GO) analysis revealed that DE genes were significantly associated with cyclic adenosine monophosphate (cAMP) metabolic process and Ca2+ binding. cAMP, a second messenger has an important role in lipolysis, and its expression is influenced by Ca2+ levels. In high-FE pigs, nine DE genes with Ca2+ binding function, were down-regulated, whereas S100G, which encodes calbindin D9K that serve as a Ca2+ bumper, was up-regulated. Furthermore, ATP2B2, ATP1A4, and VIPR2, which participate in the cAMP signaling pathway, were down-regulated in the upstream of lipolysis pathways. In high-FE pigs, the key genes involved in the lipid biosynthetic process (ELOVL7 and B4GALT6), fatty acid oxidation (ABCD2 and NR4A3), and lipid homeostasis (C1QTNF3 and ABCB4) were down-regulated. These results suggested that cAMP was involved in the regulation on FE of pigs by affecting lipid metabolism in adipose tissues.