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. 2022 Jul 9:2022:8789515.
doi: 10.1155/2022/8789515. eCollection 2022.

High Expression of TACC3 Is Associated with the Poor Prognosis and Immune Infiltration in Lung Adenocarcinoma Patients

Yan Chen  1 , Min Zhou  1 , Xuyu Gu  1 , Longfei Wang  2 , Cailian Wang  1
Affiliations

High Expression of TACC3 Is Associated with the Poor Prognosis and Immune Infiltration in Lung Adenocarcinoma Patients

Yan Chen et al. Dis Markers. .

Abstract

Background: Lung adenocarcinoma (LUAD) has been recognized as one of the commonest aggressive malignant tumors occurring in humans. The transforming acidic coiled-coil-containing protein 3 (TACC3) seems to be a probable prognostic marker and treatment target for non-small-cell lung cancer (NSCLC). Nevertheless, there exist no reports on the association between TACC3 and immunotherapy or other therapeutic interventions in LUAD.

Methods: Premised on the data accessed from The Cancer Genome Atlas- (TCGA-) LUAD, we carried out bioinformatics analysis. The TACC3 expression in LUAD was analyzed utilizing the GEPIA. A survival module was constructed to evaluate the effect of TACC3 on the survival of patients with LUAD. Logistic regression was undertaken to examine the relationship between TACC3 expression and clinical factors. Protein-protein interaction analysis was performed in the GeneMANIA database, and enrichment analysis and identification of predicted signaling pathways were performed using Gene Ontology and Kyoto Encyclopedia of Genes. Additionally, the Cox regression was used to assess the clinicopathologic features linked to the overall survival in TCGA patients. Lastly, we investigated the link between TACC3 and tumor-infiltrating immune cells (TIICs) through CIBERSORT and the "Correlation" module of GEPIA. The association between TACC3 gene expression and drug response was analyzed using the CellMiner database to predict drug sensitivity.

Results: The outcomes illustrated that TACC3 was upregulated and considerably correlated with dismal prognosis in LUAD patients. Moreover, the multivariate Cox regression analysis depicted TACC3 as an independent prognostic marker in LUAD patients. It was also revealed that the expression of TACC3 was related to clinical stage (P = 0.014), age (P = 0.002), and T classification (P ≤ 0.018). Moreover, we discovered that the expression of TACC3 was considerably linked to a wide range of TIICs, especially the T cells and NK cells. Single-cell results found that TACC3 was mainly expressed in the immune cells (especially tprolif cells) and malignant cells. TACC3 gene expression was positively correlated with TMB and MSI, and TACC3 may provide a prediction of the efficacy of immunotherapy. Moreover, the correlation analysis between TACC3 gene expression and immune checkpoint gene expression revealed that TACC3 may coordinate the activities of these ICP genes in different signal transduction pathways. TACC3 is related to biological progress (BP), cellular component (CC), and molecular function (MF). The pathways involved in the interaction network involving TACC3 include nonhomologous end-joining, RNA transport, pantothenate and CoA biosynthesis, homologous recombination, and nucleotide excision repair. Furthermore, we investigated the association between the expression of TACC3 and the use of antitumor drugs, and TACC3 was positively correlated with response to most drugs.

Conclusion: The findings from this research offer robust proof that the expression of TACC3 could be a prognostic marker correlated with TIICs in LUAD. TACC3 can also provide new ideas for immunotherapy as a potential therapeutic target.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1
Figure 1
Study workflow.
Figure 2
Figure 2
Association of TACC3 expression with clinical variables. (a) Age. (b) Gender. (c) Stage. (d) Tumor stage. (e) Lymph node metastasis. (f) Distant metastases between TACC3 expression and overall survival in LUAD patients in TCGA cohort.
Figure 3
Figure 3
Associations between TACC3 expression and clinical parameters. (a) Different expressions of TACC3 in LUAD tissue and normal tissue. (b) Different expressions of TACC3 from GEPIA analysis for verification. (c) Significant differences in TACC3 expression in different pathological stages.
Figure 4
Figure 4
Validation of protein expression of TACC3 protein in lung adenocarcinoma and adjacent tissues using immunohistochemical staining and correlation between TACC3 and the prognosis. (a) Immunohistochemical staining results of TACC3 in LUAD. (b) Expression of TACC3 protein in lung adenocarcinoma and adjacent tissues. (c) Multivariate Cox analysis of TACC3 expression and other clinicopathological features.
Figure 5
Figure 5
ROC curve for TACC3 expression in LUAD tissue and normal tissue.
Figure 6
Figure 6
Analysis of survival outcomes. (a) TACC3 expression and OS in LUAD patients in the TCGA cohort. The reduction of TACC3 expression is linked to a good prognosis. (b) Survival analysis outcomes from the GEPIA database for validation.
Figure 7
Figure 7
The outcomes of the relative proportions of TIIC that were extracted utilizing the CIBERSORT algorithm. (a) The ratio of 22 immune cells in LUAD tissues in the TACC3 low and high expression cohorts. (b) The scatterplots illustrating the purity-corrected Spearman's rho value and P value of the correlation between TACC3 and TIIC levels.
Figure 8
Figure 8
(a) A PPI network for TACC3. (b) The biological processes (BP) enrichment analysis. (c) The cellular component (CC) enrichment analysis. (d) The molecular function (MF) enrichment analysis. (e) The KEGG enrichment analysis.
Figure 9
Figure 9
Summary of PDIA3 expression of 33 cell types in 79 single cell datasets.
Figure 10
Figure 10
GSEA with KEGG pathway and GO term. (a) GO term analysis illustrated the most 5 positively linked pathways and 5 negatively linked pathways. (b) KEGG pathways illustrated the most 5 positively linked pathways and 5 negatively linked pathways.
Figure 11
Figure 11
Correlation TACC3 with TMB and MSI. (a) Correlations between TACC3 expression and tumor mutation burden in pancancer. (b) Correlations between TACC3 expression and microsatellite instability in LUAD.
Figure 12
Figure 12
The relationship between TACC3 expression and pancancer immune checkpoint genes.
Figure 13
Figure 13
An illustration of the relationship between TACC3 expression and expected medication response.
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