Insufficient ablation promotes the metastasis of residual non-small cell lung cancer (NSCLC) cells via upregulating carboxypeptidase A4

Abstract

Background Thermal ablation is a potentially curative therapy for early-stage non-small cell lung cancer (NSCLC). Early recurrence after thermal ablation necessitates our attention. Methods The invasion and migration abilities of NSCLC after sublethal heat stimulus were observed in vitro and in vivo. Sublethal thermal stimulus molecular changes were identified by RNA sequencing. A xenograft model of NSCLC with insufficient ablation was established to explore the epithelial-to-mesenchymal transition (EMT) and metastasis-related phenotypes alteration of residual tumors. Results In vitro, the invasion and migration abilities of NSCLC cells were enhanced 72 h after 44 °C and 46 °C thermal stimulus. Epithelial–mesenchymal transition (EMT) phenotypes were also upregulated under these conditions. RNA sequencing revealed that the expression of carboxypeptidase A4 (CPA4) was significantly upregulated after thermal stimulus. Significant upregulation of CPA4 and EMT phenotypes was also found in the xenograft model of insufficient NSCLC ablation. The EMT process and invasion and migration abilities can be reversed by silencing CPA4. Conclusions This study demonstrates that sublethal heat stimulus caused by insufficient ablation can promote EMT and enhance the metastatic capacity of NSCLC. CPA4 plays an important role in these biological processes. Inhibition of CPA4 might be of great significance for improving early-stage NSCLC survival after ablation.

Keywords

• nsclc
• thermal ablation
• sublethal thermal stimulus
• emt
• cpa4