Prognostic value of factors associated with hypoxia and lipid metabolism in patients with colorectal cancer

Abstract

Background: Colorectal cancer (CRC) is a neoplasia with high incidence and mortality rates. It had been suggested that the inflammatory response is an important CRC prognostic factor. The disordered and accelerated proliferation of neoplastic cells decreases the oxygen and nutrient supply, generating a microenvironment characterized by hypoxia, necrosis and inflammation. This study aimed to evaluate the impact of factors associated with hypoxia, such as HIF1A (hypoxia-inducible factor 1-alpha) and VEGF (vascular endothelial growth factor), and with lipid metabolism, including PPARG (peroxisome proliferator-activated receptor-gamma), LXRA (liver X receptor-alpha) and LXRB (liver X receptor-beta), on the overall survival (OS) of CRC patients. Methods: This was a cohort study of 101 patients with high-risk stage II-III (TNM) CRC located above the peritoneal reflection. They were treated between 1990 and 2004 at the AC Camargo Cancer Center. Immunohistochemical analyses of HIF1A, VEGF, PPARG, LXRA and LXRB protein expression were performed using tissue microarrays (TMAs). Results: There was an association between the presence of vascular invasion and the lack of VEGF expression (p = 0. 028) as well as with positive HIF1A expression and lymphatic invasion (p = 0.045). The 5-year and 10-year OS rates were 76.6% and 60.2%, respectively. Patients with PPARG-positive tumors had a higher OS (p = 0.018). There were no correlations between the positive expression of VEGF, HIF1A, LXRA or LXRB and OS. The Cox regression model demonstrated that the risk of death was 2.72-fold higher in patients with PPARG-negative tumors (95% CI = 1.08-6.85). Conclusion: The PPARG expression was an independent prognostic factor for CRC tumors and might be used for risk stratification to stage II and stage III CRC patients.

Upregulation of SLC2A3 gene and prognosis in colorectal carcinoma: analysis of TCGA data

“…Likewise, in the recent study conducted by authors’ group, the mutational status of BRAF or KRAS was not associated the prognosis of CRC [27]. For HIF , TP53 and TYMS , there are studies which reported the expression of the genes are not related to the prognosis of OS of CRC [28–30]. In this study, we also found that HIF , TP53 and TYMS were not associated with OS or DFS (Additional file 1: Table S4).…”

Colorectal Cancer and Metabolism

“…In addition to increased palmitate synthesis, CRC exhibits enhanced FA elongation [48]. Upregulation of other lipid metabolism genes, including PPARG and ACSL1, are correlated with poor prognosis in CRC [49, 50]. Silencing genes encoding sterol regulatory element-binding proteins (SREBPs) 1 and 2, which are transcription factors critical for lipogenesis, inhibited CRC growth in vitro and in xenograft models [51].…”

Integrative bioinformatics analysis of ACS enzymes as candidate prognostic and diagnostic biomarkers in colon adenocarcinoma

“…Recent studies have largely noticed the significant role of fatty acids (FAs) in the progression and development of different forms of cancers ( 8 9 10 11 ). The expression levels of different enzymes involved in the metabolism of FAs, such as FA synthase and acyl-CoA synthetase long-chain-FA-CoA ligase 1 (ACSL1), have been suggested to influence the survival, invasion, and metastasis of CRC cells and play a significant role in carcinogenesis of colorectal cancer ( 12 13 14 15 ). CRC patients with higher tumor stages have shown higher serum levels of FA synthase enzyme ( 12 ).…”