Abstract
BackgroundPancreatic cancer is the fourth leading cause of cancer deaths in the United States both in females and in males, and is projected to become the second deadliest cancer by 2030. The overall 5-year survival rate remains at around 10%. Cancer metabolism and specifically lipid metabolism plays an important role in pancreatic cancer progression and metastasis. Lipid droplets can not only store and transfer lipids, but also act as molecular messengers, and signaling factors. As lipid droplets are implicated in reprogramming tumor cell metabolism and in invasion and migration of pancreatic cancer cells, we aimed to identify lipid droplet-associated genes as prognostic markers in pancreatic cancer.MethodsWe performed a literature search on review articles related to lipid droplet-associated proteins. To select relevant lipid droplet-associated factors, bioinformatics analysis on the GEPIA platform (data are publicly available) was carried out for selected genes to identify differential expression in pancreatic cancer versus healthy pancreatic tissues. Differentially expressed genes were further analyzed regarding overall survival of pancreatic cancer patients.Results65 factors were identified as lipid droplet-associated factors. Bioinformatics analysis of 179 pancreatic cancer samples and 171 normal pancreatic tissue samples on the GEPIA platform identified 39 deferentially expressed genes in pancreatic cancer with 36 up-regulated genes (ACSL3, ACSL4, AGPAT2, BSCL2, CAV1, CAV2, CAVIN1, CES1, CIDEC, DGAT1, DGAT2, FAF2, G0S2, HILPDA, HSD17B11, ICE2, LDAH, LIPE, LPCAT1, LPCAT2, LPIN1, MGLL, NAPA, NCEH1, PCYT1A, PLIN2, PLIN3, RAB5A, RAB7A, RAB8A, RAB18, SNAP23, SQLE, VAPA, VCP, VMP1) and 3 down-regulated genes (FITM1, PLIN4, PLIN5). Among 39 differentially expressed factors, seven up-regulated genes (CAV2, CIDEC, HILPDA, HSD17B11, NCEH1, RAB5A, and SQLE) and two down-regulation genes (BSCL2 and FITM1) were significantly associated with overall survival of pancreatic cancer patients. Multivariate Cox regression analysis identified CAV2 as the only independent prognostic factor.ConclusionsThrough bioinformatics analysis, we identified nine prognostic relevant differentially expressed genes highlighting the role of lipid droplet-associated factors in pancreatic cancer.
Highlights
Pancreatic cancer is the fourth leading cause of cancer deaths in the United States both in females and in males, and is projected to become the second deadliest cancer by 2030
The selecting criteria included factors directly implicated as Lipid droplet (LD) factors, and factors localized on contact sites of LD with other organelles such as endoplasmic reticulum and mitochondria
The results revealed that up-regulation of seven genes (CAV2, CIDEC, HILP DA, HSD17B11, Neutral cholesterol ester hydrolase 1 (NCEH1), RAB5A, and Squalene epoxidase (SQLE)) and downregulation of FITM1 were significantly associated with a decrease in overall survival (OS)
Summary
Pancreatic cancer is the fourth leading cause of cancer deaths in the United States both in females and in males, and is projected to become the second deadliest cancer by 2030. As lipid droplets are implicated in reprogramming tumor cell metabolism and in invasion and migration of pancreatic cancer cells, we aimed to identify lipid droplet-associated genes as prognostic markers in pancreatic cancer. Aberrant lipid synthesis and reprogrammed lipid metabolism are both associated with the development and progression of pancreatic cancer [5]. This can be because lipids such as phospholipid bilayers are fundamental structural components enabling cellular proliferation [5]. Oncogenic KRAS, which is the most important driver for pancreatic cancer development, controls the storage and utilization of LD supporting reprogramming of tumor cell metabolism, invasion and migration [9]. Since LDassociated proteins play an important role in dynamics of LD, we hypothesized that LD-associated factors may be associated with the outcome of pancreatic cancer patients
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