Study Of Correlation Between FAS And SREBP-1c Expression In CRC Tissue And Serum Samples With Clinical Staging

Objectives:malignant cells reprogram their metabolic status to meet the needs for the rapid growth,invasion and metastasis.And demodulation of lipid metabolism is a known hallmark in these cells.Fatty acid synthase(FAS)is a central enzyme in de novo fatty acid synthesis,which normal cells do not express in high levels,and almost undetectable in otherwise healthy person's serum.But as previous studies have shown,FAS expression elevated in numerous cancer cell types such as breast,prostate,pancreatic and colorectal cancers(CRC).Upregulation of FAS expression states increased tumor cell activity and enhanced tumor cell growth and metastasis.Sterol regulatory element binding protein-1(SREBP1)is a critical regulatory molecule in lipogenesis and fatty acid synthesis,which maintains levels of FAS expression in healthy cells.It has two subtypes SREBP-1a and SREBP-1c.SREBP-1c plays a central role in the action of controlling lipogenesis via regulating several lipogenic related gene expressions including FAS.Both FAS and SREBP-1c are highly expressed in cancer tissue and serum samples in comparison with non-cancer serum and tissues samples,and this closely relates to tumor development,invasion and metastasis.In the present study,we analyze the FAS and SREBP-1c mRNA,and protein expressions in CRC and adjacent normal tissue samples as well as will evaluate serum FAS and SREBP-1c expression in CRC patients and their health counterparts.And finally,in combination with the clinicopathological features,we will analyze their correlation with tumor stage.Methods:We obtained tissue samples(cancer samples n=90,tumor-adjacent normal tissue n=55)from primary CRC patients,who underwent surgical treatment at Northern Jiangsu Peopled Hospital between January 2013 and February 2016.All had complete post-operative pathology,complete clinical data and none of them had pre-operative chemo/radiotherapy.Gross samples were acquired within 30 minutes after tumor excision and kept in appropriate temperatures for later use.We shall apply quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting(WB)techniques to analyze the FAS and SREBP-lc mRNA and protein expressions in CRC and adjacent normal tissue samples.ELISA technique will also use to evaluate serum FAS and SREBP-1c expression in CRC patients and their healthy counterparts.And finally,in combination with the clinicopathological features,we will analyze their correlation with tumor stage.Results:the expression of FAS and SREBP-1c in CRC tissue were higher than that in normal tissues,FAS was directly related to the tumor stage,and as the stage increases FAS expression elevated simultaneously(r=0.4018,P<0.001),but in the case of SREBP-1c,in stage one,showed an slight elevation,and between stage two and threethere was no significantalterationin expression levels,but when cancer developed to stage4 SREBP-1cexpression showed uprising(r=0.3126,P<0.01).In Plasma samples,the two genes expression levels were higher in cancer patients when compared to the healthy ones(FAS:16.0±0.89/10.9±0.68,SREBP-1c:51.21±2.61/44.2±2.82,P<0.01).Elevations in the two genes were not related to gender,age and tumor size.Conclusion:FAS and SREBP-1c were highly expressed in both colorectal cancer tissue and serum samples,and their expression was positively correlated with the clinical stage,except that in stage 2 and 3 SREBP-1c expression level was not reveal much difference,which suggests that the over-expression of these genes indicate high invasiveness and poor prognosis of the disease.Up-regulationof FAS and SREBP-1c expressions have impact onevaluating the biological behavior and prognosis of CRC.