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Elevated expression of protein-L-isoaspartate O-methyltransferase-1 (PCMT1) in cervical cancer - PubMed

Elevated expression of protein-L-isoaspartate O-methyltransferase-1 (PCMT1) in cervical cancer

Liyun Shan et al. Transl Cancer Res. 2022 Aug.

Abstract

Background: Protein-L-isoaspartate O-methyltransferase-1 (PCMT1) is a protein carboxyl methyltransferase enzyme, which has been found to play roles in cancers. However, no clinical information about the correlation between cervical cancer and PCMT1 expression has been reported.

Methods: We used immunohistochemistry (IHC) to characterize the protein level of PCMT1 in human cervical intraepithelial neoplasia and cervical cancer specimens. The mRNA expression profile of PCMT1 in cervical cancer was also analyzed by using Gene Expression Omnibus (GEO) databases. The prognostic value of PCMT1 in patients with cervical cancer was evaluated by using the Kaplan-Meier plotter. Gene set enrichment analysis (GSEA) was conducted by using The Cancer Genome Atlas (TCGA) cervical cancer dataset.

Results: The protein level of PCMT1 was increased in cervical high-grade squamous intraepithelial lesion (HSIL) (7.40±0.42) and cervical cancer tissues (10.70±0.54), compared to normal cervix (5.00±0.86) and low-grade squamous intraepithelial lesion (LSIL) (6.22±0.57) (P<0.05). the immunoreactivity score (IRS) of PCMT1 was also higher in cervical cancer tissues than in paired adjacent non-cancerous cervical tissues (9.03±0.52 vs. 6.32±0.46) (P<0.05). High expression of PCMT1 was associated with decreased overall survival (OS) of patients with cervical cancer (P=0.0022). GSEA demonstrated that cervical cancer patients with high expression of PCMT1 were enriched in the various cancer-related signaling pathways.

Conclusions: These results suggest that PCMT1 might be a diagnostic and prognostic biomarker for cervical cancer, and further validation studies should be performed.

Keywords: Protein-L-isoaspartate O-methyltransferase-1 (PCMT1); cervical cancer; gene set enrichment analysis (GSEA); immunohistochemistry (IHC); survival.

2022 Translational Cancer Research. All rights reserved.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-21-2700/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1

The expression of PCMT1 in cervical tissues. (A) Representative pictures of normal cervix, LSIL, HSIL and cervical cancer tissues stained with PCMT1 by IHC analysis. Scale bar =500 µm (upper) and 50 µm (lower). (B) IRS of PCMT1 in different pathological types of cervical tissues. Error bar ± SD; *P<0.05; ns, no statistically significant. LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; SCC, squamous cell carcinoma; IRS, immunoreactivity score; PCMT1, protein-L-isoaspartate O-methyltransferase-1; IHC, immunohistochemistry.

Figure 2
Figure 2

The expression of PCMT1 in cervical cancer and adjacent non-cancerous tissues. (A) Representative pictures of cervical cancer and paired adjacent non-cancerous tissues stained with PCMT1 by IHC analysis. Scale bar =500 µm (upper) and 50 µm (lower). (B) IRS of PCMT1 in cervical cancer and paired adjacent non-cancerous tissues. Error bar ± SD; *P<0.05. (C) The mRNA expression of PCMT1 between 35 cervical cancer tissues and 5 non-cervical cancer tissues (GSE7410). *P<0.05. (D) The mRNA expression of PCMT1 between 20 cervical cancer tissues and 8 normal cervical epithelium tissues (GSE6791). *P<0.05. ANT, adjacent non-cancerous tissues; IRS, immunoreactivity score; PCMT1, protein-L-isoaspartate O-methyltransferase-1; CC, cervical cancer; IHC, immunohistochemistry.

Figure 3
Figure 3

The expression of PCMT1 predicted worse survival of cervical cancer patients. (A) Kaplan-Meier OS curves in PCMT1 high and low expression cervical cancer patients from the Kaplan-Meier plotter (

https://kmplot.com/analysis/

). (B) Kaplan-Meier RFS curves in PCMT1 high and low expression cervical cancer patients from the Kaplan-Meier plotter. OS, overall survival; PCMT1, protein-L-isoaspartate O-methyltransferase-1; HR, hazard ratio; RFS, relapse-free survival.

Figure 4
Figure 4

The relationship between PCMT1 and oncogenic pathways in cervical cancer. (A) GSEA showed the correlation between PCMT1 expression and HALLMARK gene sets in cervical cancer based on TCGA data. (B) GSEA showed the correlation between PCMT1 expression and KEGG pathway gene sets in cervical cancer based on TCGA data. FDR, false discovery rate; PCMT1, protein-L-isoaspartate O-methyltransferase-1; GSEA, gene set enrichment analysis; TCGA, The Cancer Genome Atlas; KEGG, Kyoto Encyclopedia of Genes and Genomes.

Figure 5
Figure 5

The relationship between PCMT1 and carcinogenic signaling related genes in cervical cancer. (A) GEPIA2 (

http://gepia2.cancer-pku.cn/#index

) showed the correlation between the expression of PCMT1 and Myc target genes (TCP1, HDAC1, PWP1, CDC20 and PTGES3) in cervical cancer. (B) GEPIA2 showed the correlation between the expression of PCMT1 and PI3K/Akt/mTOR signaling (CDK4, PDK1, ATF1, EIF4E and UBE2N) in cervical cancer. (C) GEPIA2 showed the correlation between the expression of PCMT1 and EMT signaling (TGF-β1, MMP14, LGALS1, VEGFA and AREG) in cervical cancer. PCMT1, protein-L-isoaspartate O-methyltransferase-1; TPM, transcripts per million; EMT, epithelial mesenchymal transition; GEPIA2, Gene Expression Profiling Interactive Analysis 2.

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