Our ‘Dataset of the Week’ series features publicly available omics datasets of scientific value, intending to promote data sharing and reuse.

This week, we feature a microarray dataset generated on an Affymetrix whole transcript array from the publication titled ‘NAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis’1.

Primary cancer of the liver or hepatocellular carcinoma (HCC) is the world’s second leading cause of cancer-related deaths in humans2. HCC is commonly considered an inflammation-related cancer but recent epidemiological studies have indicated that obesity-related nonalcoholic fatty liver disease (NAFLD) has a significant impact on the promotion and risk factors of HCC3,4. The mechanism of NAFLD’s contribution in the formation of carcinogenic hepatocytes was explored in this publication. Researchers used a microarray-based approach to examine the effects of excess production of intrahepatic lipids and the resulting immune responses in the microenvironment of hepatocytes.

Key Findings of the Publication:

1. Dysregulation of lipid metabolism in NAFLD was observed to disrupt the liver immune surveillance mechanism, which accelerated the process of hepatocarcinogenesis.
2. Global transcriptomic array profiling and pathway analysis revealed that accumulation of linoleic acid disrupted mitochondrial function and caused apoptosis and significant loss of intrahepatic CD4+ T lymphocytes.
3. Validation with quantitative real-time PCR confirmed the gene changes reported in microarray profiling and linoleic acid’s role in the disruption of the oxidative phosphorylation mechanism in T lymphocytes.

Significance of the Dataset:

This dataset contains microarray data from murine liver tissues exposed to intrahepatic lipids, replicating liver conditions of nonalcoholic fatty liver disease (NAFLD). Exploring this transcriptome could shed more light on novel metabolic factors affecting tissue health in liver cells.

Experimental Design:

Splenocytes were isolated from transgenic mice that were fed either normal chow or a fatty acid-rich diet (n=5 control, n=6 experimental group). CD4+ and CD8+ T lymphocytes were sorted from these splenocytes. Total RNA was extracted from these samples and microarray analysis was carried out using the Affymetrix platform.

Useful links:

1. The dataset (GSE67918)
2. The publication

References:

1. Ma, Chi et al. “NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis.” Nature vol. 531,7593, 253-7 (2016).
2.  Park JW, Chen M, Colombo M, et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int vol. 35, 2155-66 (2015).
3. Blonski W, Kotlyar DS, Forde KA. Non-viral causes of hepatocellular carcinoma. World J Gastroenterol vol. 16, 3603-15 (2010).
4. Bianchini F, Kaaks R, Vainio H. Overweight, obesity, and cancer risk. Lancet Oncol vol. 3, 565-74 (2002).