Dataset Information

Elovl6 is a negative clinical predictor for liver cancer and knockdown of Elovl6 reduces murine liver cancer progression.

ABSTRACT: The elongation of long-chain fatty acids family member 6 (Elovl6) is a key enzyme in lipogenesis that catalyzes the elongation of saturated and monounsaturated fatty acids. Insulin resistance involves upregulation of Elovl6, which has been linked to obesity-related malignancies, including hepatocellular carcinoma (HCC). However, the role of Elovl6 in cancer progression remains unknown. In this study, we analyzed the expression of Elovl6 in 61 clinical HCC specimens. Patients with Elovl6 high-expressing tumors were associated with shorter disease-free survival and overall survival compared to those with Elovl6 low-expressing tumors. Knockdown of Elovl6 in HCC cells reduced cell proliferation and Akt activation, as well as sensitivity to fatty acids. Inhibition of Elovl6 reduced tumor growth and prolonged survival in mice bearing tumors. Taken together, our results indicate that Elovl6 enhances oncogenic activity in liver cancer and is associated with poor prognosis in patients with HCC. Elovl6 may be a therapeutic target for HCC; thus, further studies to confirm this strategy are warranted.

SUBMITTER: Su YC

PROVIDER: S-EPMC5920119 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Elovl6 is a negative clinical predictor for liver cancer and knockdown of Elovl6 reduces murine liver cancer progression.

Su Yu-Chu YC Feng Yin-Hsun YH Wu Hung-Tsung HT Huang Yao-Shen YS Tung Chao-Ling CL Wu Pensee P Chang Chih-Jen CJ Shiau Ai-Li AL Wu Chao-Liang CL

Scientific reports 20180426 1

The elongation of long-chain fatty acids family member 6 (Elovl6) is a key enzyme in lipogenesis that catalyzes the elongation of saturated and monounsaturated fatty acids. Insulin resistance involves upregulation of Elovl6, which has been linked to obesity-related malignancies, including hepatocellular carcinoma (HCC). However, the role of Elovl6 in cancer progression remains unknown. In this study, we analyzed the expression of Elovl6 in 61 clinical HCC specimens. Patients with Elovl6 high-exp ...[more]

PMID: 29700319

Similar Datasets

Project description:BACKGROUND:Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype with basal features, lacking the expression of receptors targeted successfully in other breast cancer subtypes. Treatment response to adjuvant and neoadjuvant chemotherapy is often short-lived and metastatic spread occurs at higher rates than other subtypes within the first five years after diagnosis. TNBCs exhibit stem cell features and are enriched for cancer stem cell (CSC) populations. E1A Binding Protein P300 (EP300) is a large protein with multiple cellular functions, including as an effector in stem cell biology. METHODS:We used a genetic knockdown (KD) model of EP300 in TNBC cell lines to investigate the effect on CSC phenotype, tumor growth and metastasis. Side population assay and tumorsphere suspension culture were used in vitro. Xenograft mouse models were used for in vivo studies. We performed in silico analysis of publicly available gene expression data sets to investigate CSC gene expression and molecular pathways as well as survival outcomes associated with EP300 expression in patients with TNBC and basal-like BC. RESULTS:EP300 KD abolished the CSC phenotype by reducing ABCG2 expression, side population cells and tumorsphere formation capacity in vitro as well as tumor formation in a xenograft mouse model in vivo. Metastatic capacity was markedly reduced in EP300 KD cells in vivo, with no detection of circulating tumor cells. TCGA data analysis demonstrated that genes positively correlated with EP300 expression in TNBC and basal-like BC were associated with CSC biology. Survival analysis demonstrated that EP300 expression predicts poor recurrence free survival in TNBC and basal BC. CONCLUSION:We report a novel oncogenic role for EP300 in driving CSC phenotype representing a potential target to address tumor initiation and metastatic spread in TNBC and basal-like BC. EP300 might serve as a prognostic marker and potential therapeutic target in TNBC.

Project description:BackgroundTriple-negative breast cancer is a subtype of breast cancer with aggressive tumor behavior and distinct disease etiology. Due to the lack of an effective targeted medicine, treatment options for triple-negative breast cancer are few and recurrence rates are high. Although various multi-gene prognostic markers have been proposed for the prediction of breast cancer outcome, most of them were proven clinically useful only for estrogen receptor-positive breast cancers. Reliable identification of triple-negative patients with a favorable prognosis is not yet possible.Methodology/principal findingsClinicopathological information and microarray data from 157 invasive breast carcinomas were collected at National Taiwan University Hospital from 1995 to 2008. Gene expression data of 51 triple-negative and 106 luminal breast cancers were generated by oligonucleotide microarrays. Hierarchical clustering analysis revealed that the majority (94%) of triple-negative breast cancers were tightly clustered together carrying strong basal-like characteristics. A 45-gene prognostic signature giving 98% predictive accuracy in distant recurrence of our triple-negative patients was determined using the receiver operating characteristic analysis and leave-one-out cross validation. External validation of the prognostic signature in an independent microarray dataset of 59 early-stage triple-negative patients also obtained statistical significance (hazard ratio 2.29, 95% confidence interval (CI) 1.04-5.06, Cox P=0.04), outperforming five other published breast cancer prognostic signatures. The 45-gene signature identified in this study revealed that TGF-? signaling of immune/inflammatory regulation may play an important role in distant metastatic invasion of triple-negative breast cancer.Conclusions/significanceGene expression data and recurrence information of triple-negative breast cancer were collected and analyzed in this study. A novel set of 45-gene signature was found to be statistically predictive in disease recurrence of triple-negative breast cancer. The 45-gene signature, if further validated, may be a clinically useful tool in risk assessment of distant recurrence for early-stage triple-negative patients.

Dataset Information

Elovl6 is a negative clinical predictor for liver cancer and knockdown of Elovl6 reduces murine liver cancer progression.

Publications

Elovl6 is a negative clinical predictor for liver cancer and knockdown of Elovl6 reduces murine liver cancer progression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets