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.

中文翻译：

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消融不足通过上调羧肽酶A4促进残留非小细胞肺癌（NSCLC）细胞的转移

摘要

背景

热消融是早期非小细胞肺癌（NSCLC）的潜在治愈性疗法。热消融后的早期复发需要我们的关注。

方法

体外和体内观察亚致死热刺激后NSCLC的侵袭和迁移能力。通过 RNA 测序鉴定了亚致死的热刺激分子变化。建立消融不充分的非小细胞肺癌异种移植模型，探讨残留肿瘤的上皮间质转化（EMT）和转移相关表型改变。

结果

在体外，44℃和46℃热刺激72小时后，NSCLC细胞的侵袭和迁移能力增强。在这些条件下，上皮 - 间质转化（EMT）表型也被上调。RNA测序显示羧肽酶A4（CPA4）的表达在热刺激后显着上调。在 NSCLC 消融不足的异种移植模型中也发现了 CPA4 和 EMT 表型的显着上调。EMT 过程和入侵和迁移能力可以通过沉默 CPA4 来逆转。

结论

本研究表明，消融不充分引起的亚致死热刺激可促进 EMT，增强 NSCLC 的转移能力。CPA4 在这些生物过程中发挥着重要作用。抑制 CPA4 可能对提高早期 NSCLC 消融后的存活率具有重要意义。