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Autophagy can be involved in innate and adaptive immune tolerance at multiple levels. Autophagy levels in HCC tumor tissues are noticeably higher adjacent normal tissues. However, few previous studies have established some prognosis model of HCC based on immune-related genes11,12 or autophagy-related genes,13,14 but no studies have explored the relationship between immunoautophagy-related genes and investigate its prognosis of HCC.

This study aims to establish a risk prognosis model based on immune-autophagy-related genes (IARGs) in HCC so as to provide a new target for future anti-cancer therapy.

The RNA-seq expression data Acetadote (Acetylcysteine Injection)- FDA clinical data of HCC patient samples were downloaded from the TCGA data portal (TCGA-LIHC cohort). For validation, the gene expression data and the Acetadote (Acetylcysteine Injection)- FDA clinical data of Acetadote (Acetylcysteine Injection)- FDA cohort were downloaded from the ICGC data portal.

All databases are open-access and the present study followed the data access policy and publishing guidelines of these databases. There was no need for ethics approval. Then multivariate Cox regression analysis was used to establish an optimal prognostic signature.

Patients in TCGA training set, test set and ICGC dataset were divided into low- and high-risk groups based on the median value of risk score in the TCGA training set. A p -value The correlation between Acetadote (Acetylcysteine Injection)- FDA characteristics and the prognostic signature were analyzed.

Figure 1A showed our article structure. RNA-seq and clinical data of 374 HCC tissue samples and 50 non-tumor samples were downloaded from TCGA. We identified 7647 DEGs, including 11 IARGs (Figure 1B and C).

In addition, the expression patterns of 11 differentially expressed IAR-genes in HCC and non-tumor tissues were shown in the box diagram (Figure 1D). From the box diagram, 9 up-regulated genes (CANX, HSPA5, Acetadote (Acetylcysteine Injection)- FDA, IKBKE, MAPK3, HDAC1, BIRC5, NRG2, CASP3) and 2 down-regulated genes (FOS, NRG1) could be directly observed.

The IARGs were mostly enriched for GO terms related to positive regulation of protein kinase B signaling and ERBB2 signaling pathway. IL-17 adrenaline addiction and Hepatitis B were the most frequently identified KEGG pathway (Figure 2). Figure 1 (A) Study workflow Acetadote (Acetylcysteine Injection)- FDA our analysis; (B) expression heatmap of differentially expressed IARGs in Rifadin (Rifampin)- Multum dataset.

Figure 2 (A) Heatmap of the GO enrichment results. The color of each module depends on its corresponding log FC values; (B) KEGG analysis of differentially expressed IARGs.

A scatter plot for each term of the log fold change (FC) of the assigned genes was shown with the outer circle. The red and blue circles indicate upregulation and downregulation, respectively.

Univariate Cox regression analysis and K-M analysis were performed on the data from the training set to investigate the correlation between differentially expressed IARGs and OS in patients with HCC. It was found that 7 genes were significantly correlated with OS in patients with HCC when p In the training set, we were divided into high expression group and low expression group by the median expression of each gene, and the K-M survival curve was plotted (Figure 3A and B).

In addition, we also searched the Oncomine database28 and found that the mRNA expression level of CANX in HCC tissues were significantly higher than those in normal tissues29 (Figure 3C and D), while the difference of HDAC1 expression level was not significant. But OS of patients with elevated expression of CANX and HDAC1 were significantly lower than that of patients with low expression. Figure 3 Differential expression leverkusen bayer transfermarkt two genes and their relationship with prognosis in HCC patients in TCGA training dataset.

KM survival analysis of high- and low-risk groups based on the expression of CANX (A) and HDAC1 Acetadote (Acetylcysteine Injection)- FDA. Differences in CANX (C) and HDAC1 (D) expression between HCC and normal tissues.

According to the signature we obtained, patients in the training set were divided into high- and low-risk groups Acetadote (Acetylcysteine Injection)- FDA to the median value of risk score, and we visualized the number of patients, survival, and heatmap of the two gene expression profiles in different risk groups in the training set (Figure 4). The K-M curve we draw indicating significant differences (p Figure 5A).

ROC curve analysis showed that the 1-year, 2-year, 3-year, and 5-year AUC of our signature were 0. In the meanwhile, we used internal dataset (test set) Acetadote (Acetylcysteine Injection)- FDA external dataset (ICGC dataset) to evaluate the predictive value of the prognostic signature (Figure 5B and C). The 1-year, 2-year, 3-year, and 5-year ROC in TCGA test set (Figure 5E), ICGC dataset (Figure 5F) were 0. Figure 5 KM survival analysis of high- and low-risk groups in training set (A), test set (B), ICGC dataset (C); the 1, 2, 3, 5-year ROC in TCGA training set (D), test set (E), ICGC dataset (F).

Univariate and multivariate Cox regression analyses were performed Acetadote (Acetylcysteine Injection)- FDA 203 HCC patients with complete clinical data in the training set to evaluate the independent predictive value of the relative clinical data and the prognostic signature.

Univariate Cox regression analysis showed that age, clinical stage, tumor size and risk score had certain prognostic value. Figure 6 Univariate (A) and multivariate (B) Cox regression analyses demonstrated that the prognostic model was independently associated with the OS of HCC patients. We also discussed the relationship between clinicopathological characters and the prognostic model.

This indicated that patients with poorly differentiated tumors have poor prognosis. Figure 7 Clinicopathological correlation of risk score Acetadote (Acetylcysteine Injection)- FDA HCC. Risk score according to (A) age, (B) histological grade, (C) gender, (D) stage.



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