Obstet Gynecol Sci.  2022 Jan;65(1):52-63. 10.5468/ogs.21237.

Signature of arylacetamide deacetylase expression is associated with prognosis and immune infiltration in ovarian cancer

• Feng J
• He H

• KMID: 2524685
• DOI: http://doi.org/10.5468/ogs.21237

Abstract

Objective
The role of the protein-coding gene arylacetamide deacetylase (AADAC) in the prognostication of ovarian cancer remains uncertain. We aimed to identify and validate its prognostic value using integrated bioinformatics analyses.
Methods
Gene expression profiles of RNA-sequencing and microarray data were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus. Univariate and multivariate Cox regression models were used to evaluate the prognostic value of gene expression. The predictive accuracy of the gene signature model was evaluated using a time-dependent receiver operating characteristic (ROC) curve. In addition, the correlation between immune infiltration and AADAC was identified. A nomogram of the gene signature with clinical parameters was constructed to estimate the clinical application of the signature for survival prediction in patients with ovarian cancer.
Results
Univariate and multivariate Cox regression analyses in the training and validation cohorts indicated that a high AADAC expression signature was significantly and independently correlated with better survival outcomes in ovarian cancer. AADAC upregulation positively correlated with the infiltration of CD4+ memory T cells. Immunological signature gene sets were significantly enriched in CD4+ T cell regulation pathways. The area under the curve of the time-dependent ROC for overall survival indicated that the constructed nomogram had a moderate predictive ability for prognostic prediction in ovarian cancer.
Conclusion
AADAC expression signature significantly and independently correlated with the survival outcome and CD4+ memory T cell infiltration in ovarian cancer, indicating its potential applicability in the prediction of prognosis and immunotherapy efficacy.

Keyword

Arylacetamide deacetylase; Ovarian neoplasms; Computational biology; Tumor microenvironment; Nomogram

Figure

• 

  Fig. 1 Differentially expressed protein-coding genes in ovarian cancer. (A) Volcano plots of the differentially expressed genes. (B, C) Intersection of the upregulated and downregulated protein-coding genes in the GSE18520 and GSE26712 datasets. (D, E) Principal component analysis plots for performing the batch effect control. (F–H) LASSO-penalised Cox regression analyses for differentially expressed and survival-related protein-coding genes. DEG, differentially expressed gene; LASSO, least absolute shrinkage and selection operator; TCGA-OV, The Cancer Genome Atlas-ovarian cancer.

• 

  Fig. 2 Univariate and multivariate Cox regression analyses in (A) the training and (B) validation cohorts. CI, confidence interval; IDH2, isocitrate dehydrogenase ; FANCI, FA complementation group I; CXCR4, C-X-C motif chemokine receptor 4; PRAME, PRAME nuclear receptor transcriptional regulator; PJA2, praja ring finger ubiquitin ligase 2; ECI2, enoyl-CoA delta isomerase 2; AADAC, arylacetamide deacetylase. *P <0.05, **P <0.01.

• 

  Fig. 3 Kaplan-Meier plot and evaluation of the arylacetamide deacetylase (AADAC ) signature score in ovarian cancer. (A, D) Kaplan-Meier plot of the AADAC signature score in the training and validation cohorts. (B, E) Time-dependent ROC curve of the AADAC signature score. (C, F) Multivariate Cox regression analysis of the AADAC signature score. ROC, receiver operating characteristic; CI, confidence interval; FIGO, The International Federation of Gynecology and Obstetrics. *P <0.05, **P <0.01, ***P <0.001.

• 

  Fig. 4 Correlation of the arylacetamide deacetylase (AADAC ) expression with immune infiltration and immunological signature in ovarian cancer. (A, B) An increased extent of CD4+ memory T cell infiltration was significantly correlated with the upregulation of AADAC. (C) Kaplan-Meier plot illustrating CD4+ memory T cell infiltration. (D) CD4+ T cell enrichment analysis in the immunological signature. CI, confidence interval; NES, normalized enrichment score.

• 

  Fig. 5 Nomogram model and evaluation of the arylacetamide deacetylase (AADAC ) expression signature with clinicopathologic parameters in ovarian cancer. (A) Nomogram model of the AADAC expression signature with clinicopathologic parameters. (B–D) Calibration curves of the nomogram model for 1-, 3-, and 5-year survival. (E) Time-dependent ROC curves of the nomogram model for 1-, 3-, and 5-year survival. OS, overall survival; ROC, receiver operating characteristic.

Reference

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