Downregulated expression of plakophilin-2 gene in patients with colon adenocarcinoma predicts an unfavorable prognosis and immune infiltrate

J Gene Med. 2024 Jan;26(1):e3592. doi: 10.1002/jgm.3592. Epub 2023 Sep 19.

Abstract

Background: Plakophilin 2 gene (PKP2) has been revealed to be differentially expressed in various cancer types and is correlated with prognosis. However, the role of PKP2 in colon adenocarcinoma remains indistinct.

Methods: Differences in transcriptional expression of PKP2 between colon adenocarcinoma tissues and normal adjacent tissues were acquired from the publicly available dataset-the Cancer Genome Atlas. A receiver operating curve (ROC) was constructed to differentiate colon adenocarcinoma tissues from adjacent normal tissues. The Kaplan-Meier plot method was performed to evaluate the effect of PKP2 on survival. The correlation between mRNA expression of PKP2 and immune infiltrating was determined by the Tumor Immune Estimation Resource and Tumor-Immune System Interaction databases.

Results: The expression of PKP2 in colon adenocarcinoma tissues was significantly downregulated compared with corresponding adjacent normal tissues. Decreased PKP2 mRNA expression was associated with lymph node metastases and advanced pathological stage. The ROC curve analysis indicated that with a cutoff value of 6.034, the sensitivity and specificity for PKP2 differentiating the colon adenocarcinoma tissues from the adjacent normal tissues were 90.2 and 66.5% respectively. Kaplan-Meier plot survival analysis revealed that colon adenocarcinoma patients with low-PKP2 had a worse prognosis than those with high-PKP2 (68.2 vs. 101.4 months, p = 0.028). Correlation analysis showed that mRNA expression of PKP2 was correlative with immune infiltrates.

Conclusions: Downregulated PKP2 is significantly correlated with unfavorable immune infiltrating and survival in colon adenocarcinoma. This research indicates that PKP2 can be selected as a novel biomarker of potential immunotherapy targets and unfavorable prognosis in colon adenocarcinoma.

Keywords: PKP2; biomarker; colon adenocarcinoma; immune infiltrates; prognosis.

MeSH terms

  • Adenocarcinoma* / genetics
  • Colonic Neoplasms* / diagnosis
  • Colonic Neoplasms* / genetics
  • Humans
  • Immunotherapy
  • Plakophilins / genetics
  • RNA, Messenger / genetics

Substances

  • Plakophilins
  • RNA, Messenger
  • PKP2 protein, human