The prognostic value of TPM1-4 in hepatocellular carcinoma

Abstract

Background: Despite advances in multiple disciplinary diagnoses and treatments, the prognosis of hepatocellular carcinoma (HCC) remains poor. Some evidence has identified that the aberrant expression of tropomyosins (TPMs) is involved with some cancers development. However, prognostic values of TPMs in HCC have not been thoroughly investigated.

Methods: Original TPM1-4 mRNA expression of TCGA HCC data and GTEx was downloaded from UCSC XENA. Oncomine database and GSE46408 were used for verification. Clinical stages and survival analysis of TPM1-4 in HCC were performed by GEPIA2. cBioPortal was utilized to assess TPM1-4 gene alteration in HCC. TIMER2.0 was used for investigating the relevance of TPM1-4 to tumor-infiltrating immune cells in HCC. Additionally, we constructed a TPM1-4 prognostic model to explore the value of TPM1-4 for prognostic evaluation in HCC. LinkedOmics was applied to elucidate TPM3 co-expression networks in HCC.

Results: This present study showed that TPM1-4 was upregulated in all HCC tissues, and TPM3 overexpression was correlated with poor survival outcomes in patients with HCC. Besides, TPM3 amplification was the main altered type in TPM1-4 genetic alteration, which affected the prognosis of HCC patients. The risk model revealed that TPM1, TPM2, and TPM3 were applied to risk assessment of HCC prognosis, among which TPM3 expression was significantly higher in the high-risk group than that in the low-risk group. Univariate and multivariate cox regression analyses indicated that TPM3 may be an independent prognostic factor of HCC prognosis. In addition, TPM3 co-expression genes mainly participated in the cell cycle by maintaining microtubule cytoskeleton in HCC progression. TPM1-4 was associated with some tumor-infiltrating immune cells in HCC.

Conclusion: Our study detected that the expression level of TPM1-4 was all remarkably elevated in HCC, suggesting that TPM1-4 may serve an important role in HCC development. High TPM3 expression was found to be correlated with poor overall survival, and TPM3 may be an independent prognostic factor for HCC.

Keywords: bioinformatics analysis; hepatocellular carcinoma; prognosis; risk model; tropomyosins.

FIGURE 1

Flowchart of the study procedures

FIGURE 2

TPM1‐4 expression in HCC. (A) TPM1–4 expression in HCC tissues and normal tissues from TCGA and GTEx data (***p < 0.001). (B) The correlation between TPM1–4 and clinical stage in HCC patients (GEPIA2). HCC, hepatocellular carcinoma; TPM, tropomyosin

FIGURE 3

The correlation between TPM1–4 and OS in HCC (GEPIA2). HCC, hepatocellular carcinoma; OS, overall survival; TPM, tropomyosin

FIGURE 4

Genetic alteration of TPM1–4 in HCC. (A) Frequency of gene alterations in TPM1–4 in HCC. (B) Genetic alterations in TPM1–4 were related to shorter PFS (p < 0.05) and OS (p < 0.01) of HCC patients, no significant differences in DFS. DFS, disease‐free survival; HCC, hepatocellular carcinoma; OS, overall survival; PFS, progression‐free survival; TPM, tropomyosin

FIGURE 5

The prognostic values of the risk model in HCC. (A) The risk score of HCC patients in high‐ and low‐risk groups, the related genes expression was shown in heat maps. (B) Kaplan–Meier survival curve demonstrated that patients with high‐risk scores were correlated with worse overall survival. (C) The ROC curve of related genes with the AUC in HCC (0.753, 1‐year OS; 0.652, 3‐year OS; and 0.614, 5‐year OS). AUC, area under the curve; HCC, hepatocellular carcinoma; OS, overall survival; ROC, receiver operating characteristic

FIGURE 6

Univariate and multivariate Cox regression analyses of TPM1–4 and other clinicopathologic factors in HCC. (A) Correlation of TPM1–4 with each other in HCC (Spearman's correlation values, cBioPortal). (B) The forest plot for TPM1–4 and other clinicopathologic factors in HCC. HCC, hepatocellular carcinoma; TPM, tropomyosin

FIGURE 7

TPM3 co‐expression genes in HCC (LinkedOmics). (A) The Pearson test was used to identify genes differentially expressed in correlation with TPM3 in HCC. (B, C) Heat map demonstrated 50 significant genes positively and negatively correlated with TPM3 in HCC. HCC, hepatocellular carcinoma; TPM, tropomyosin

FIGURE 8

GO (biologic process) terms and KEGG pathway related to TPM3 in HCC (LinkedOmics). (A) The significantly enriched GO annotations (biologic process) of TPM3 in HCC. (B) The KEGG pathways of TPM3 in HCC. GO, Gene Ontology; HCC, hepatocellular carcinoma; KEGG, Kyoto Encyclopedia of Genes and Genomes; TPM, tropomyosin

FIGURE 9

The score distribution of tumor‐infiltrating immune cells in HCC. Twenty‐two kinds of tumor‐infiltrating immune cells CIBERSORT score distribution in HCC tissues and normal tissues (*p < 0.05, ***p < 0.001)

FIGURE 10

Association between TPM1–4 and tumor‐infiltrating immune cells in HCC (TIMER2.0). Tumor purity was shown on the left panel. The correlation between TPM1–4 and tumor‐infiltrating immune cells (B cell, CD4+ T cell, CD8+ T cell, Tregs, macrophage, neutrophil, dendritic cell, and cancer‐associated fibroblast) were shown in HCC. HCC, hepatocellular carcinoma; TPM, tropomyosin