## 4 Results and Discussion
### Signal Profiles and P-Values of Extracted Key Genes
COLIA1 can suppress the clonogenicity of HCC cells and help in the early survival of the HCC and play a great role in the target therapy of HCC [42]. The univariate methods, Pearson correlation, cosine coefficient, and Euclidean distance, have also yielded a similar list of key genes. KLF2 is the most significant key gene that has been detected using these methods. Its signal profile was as a downregulated gene in the infected tissues. The protein expression of KLF2 was enlarged in HCC cells [43] ASNS, TXNIP, and PCK2 have been detected downregulated also, with significant p values, according to Figure 5. The PCK2 gene has been reported as a downregulated gene in primary HCC and a forced expression of PCK2 was suppressed the HCC tumorigenesis in an experiment on mice [44]. OARD1, SPRY1, and ZNF691 are downregulated detected genes. The role of OARD1 has been investigated in [45]. SPRY1 is related to the Sprouty Protien and has been investigated in [46]. They revealed that its expression is overexpressed in HCC. The role of ZNF691 gene in the HCC tumorigenesis has not been investigated yet. CYP1A1, from cytochrome P450 family 1, has been detected as downregulated in the first period of post-infection. A study on the contribution of CYP1A1 in the risky outcomes of an HCV-infected patient was done in [47]. They investigated the impact of polymorphisms of the CYP family of genes on the progression of liver diseases. Their study showed that Polymorphic modifications of CYP family genes could result in the development of liver infection and occurrence of HCC risk. MAFF and CCDC86 were insignificant according to their P values, shown in Figure 5. MAFF has been detected in the first and second periods of post-infection. MAFF regulates a diversity of goal genes, including genes responsible for platelet production and genes responsible for antioxidant/xenobiotic enzyme. MAFF has been conveyed in the regulation of the oxytocin gene. However, the involvement of MAFF within the regulation of genes and proteins significant for HCV and HCC has not been inspected to date [48]. CCDC86 has a contribution in the formation of HCV [49]. By using the Euclidean distance gene selection method, a lower number of significant genes were retrieved, according to P values, as shown in Figure 6. CYP1A1, MAFF, and PCK2 genes have been retrieved. CTH, BCAT1, EREG, PHLDA1, and AGR2 have been retrieved as downregulated genes with significant P values. CTH has been differentially expressed in normal and tumor HCC tissues [50]. BCAT1 has a highly significant expression in HCC samples compared to normal samples, as stated in [51], EREG has contributed in the hepatocarcinogenesis, as testified in [52], PHLDA1 has been detected as a novel biomarker of HCC, as it expressed differentially in the experiment done in [53], and AGR2 has high expression values in metastatic hepatocellular carcinoma samples, as found in [54]. Other retrieved genes, including SLC19A1, CCDC127, and MAFF, were unexpressed differentially according to their P values. Using PCA, several HCC biomarkers (EEF1A1, ATP6, and FTL) have been detected in the four periods of post-infection with C virus, as shown in Table 4. EEF1A1 is a well-known HCC biomarker and is considered one of the top 20 genes related to human hepatocarcinoma cell lines. EEF1A1 has been reported as a novel prognosis biomarkers for liver cancer using a multivariate analysis done in [55]. In our experiment, EEF1A1 was retrieved as a down-regulated gene with a significant p value, as illustrated by Figure 7. However, ATP6, and FTL were unexpressed, with p values > 0.005. RPS2 was downregulated with a significant p value. RPS2 was founded in [56] as a significant key gene for HCC. ACTB gene has been detected as upregulated with a significant p values. ACTB was expressed differentially in the study done in [57]. Although the other retrieved genes were related to liver diseases (HCV, and HCC) in the biological literature [58; 59; 60], including COX1, COX2, KRT18, PPIA, UBC, and MTND4, they were unexpressed in this study.