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Tumor Discovery                                                       DRGs in HCC prognosis and immunity



            tissues, which is crucial for elucidating tumorigenesis,   NCKAP1,  CD2AP,  ACTB, and  ACTN4) exhibited
            progression, and therapeutic outcomes. To investigate the   significant prognostic value (threshold of p<0.01, HR > 1)
            relationship between DRG expression and immune cell   (Figure  2A). LASSO regression analysis was utilized to
            infiltration, we submitted differentially expressed DRGs   select  the  optimal  parameter  (Lambda)  for  the  model.
            to the database (https://cistrome.shinyapps.io/timer/) to   Cross-validation was performed by selecting one standard
            acquire information regarding the association between   error of the Lambda value, resulting in the most optimal
            genes and immune cells. A higher correlation coefficient
            (Cor) indicates a stronger relationship between genes and   A
            immune cell infiltration.
            2.9. Drug sensitivity analysis
            Six  DRGs  were  submitted  to  the  Genomics  of  Drug
            Sensitivity in Cancer (GDSC) and the Cancer Therapeutics
            Response Portal (CTRP) through the Gene Set Cancer
            Analysis (GSCA) website (http://bioinfo.life.hust.edu.
            cn/GSCA/#/), which facilitated a more in-depth analysis
            of the relationship between DRG expression and drug
            sensitivity in HCC.

            3. Results
            3.1. Construction and validation of a prognostic
            model based on DRGs                                 B
            3.1.1. Heatmap of gene expression levels between
            normal and tumor tissue

            Based on |logFC| >0.5 and a FDR threshold of <0.05, 23
            known genes were initially screened. Subsequently, the
            “limma” package in the R software was utilized to identify
            genes with differential expression. Through this analysis,
            18 DRGs, including  SLC7A11,  PDLIM1,  GYS1,  ACTN4,
            NDUFA11,  NCKAP1,  FLNB,  MYH9,  MYL6,  LRPPRC,
            SLC3A2,  FLNA,  CD2AP,  RPN1,  ACTB,  CAPZB,  DSTN,
            and TLN1, were identified. A heatmap was generated using
            clinical information from HCC patients to display the
            expression levels of the 18 genes in both normal and tumor
            tissues. Analysis of the left dendrogram of the heatmap   C
            revealed that  SLC7A11,  CD2AP,  GYS1, and  NCKAP1
            exhibited high similarity and were minimally expressed in
            normal tissues. In addition, the relative expression levels of
            ACTB were higher in both normal and tumor tissues. The
            expression levels of MYL6 and RPN1 were upregulated in
            most tumor tissues. In contrast, FLNA, ACTN4, CAPZB,
            and  DSTN were downregulated in some tumor tissues
            (Figure 1). The heatmap visually represents specific gene
            expression (the left dendrogram indicates gene clustering,
            and  the  color  blocks  reflect  relative  gene  expression),
            facilitating further analysis.

            3.1.2. Univariate Cox regression and LASSO regression
            Univariate Cox regression analysis was employed to   Figure 2. Correlation graphs of univariate Cox regression and LASSO
                                                               regression. (A)  Forest  map.  (B) LASSO  coefficient  path  diagram.
            assess the prognostic significance of HCC. It was found   (C) Cross-validation used in the LASSO regression.
            that only eight genes (CAPZB,  RPN1,  SLC7A11,  FLNA,   Abbreviation: LASSO: Least absolute shrinkage and selection operator.


            Volume 4 Issue 2 (2025)                         70                                doi: 10.36922/td.8214
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