PMS2 amplification contributes brain metastasis from lung cancer.

Abstract

Background: Lung adenocarcinoma metastasizing to the brain results in a notable increase in patient mortality. The high incidence and its impact on survival presents a critical unmet need to develop an improved understanding of its mechanisms.

Methods: To identify genes that drive brain metastasis of tumor cells, we collected cerebrospinal fluid samples and paired plasma samples from 114 lung adenocarcinoma patients with brain metastasis and performed 168 panel-targeted gene sequencing. We examined the biological behavior of PMS2 (PMS1 Homolog 2)-amplified lung cancer cell lines through wound healing assays and migration assays. In vivo imaging techniques are used to detect fluorescent signals that colonize the mouse brain. RNA sequencing was used to compare differentially expressed genes between PMS2 amplification and wild-type lung cancer cell lines.

Results: We discovered that PMS2 amplification was a plausible candidate driver of brain metastasis. Via in vivo and in vitro assays, we validated that PMS2 amplified PC-9 and LLC lung cancer cells had strong migration and invasion capabilities. The functional pathway of PMS2 amplification of lung cancer cells is mainly enriched in thiamine, butanoate, glutathione metabolism.

Conclusion: Tumor cells elevated expression of PMS2 possess the capacity to augment the metastatic potential of lung cancer and establish colonies within the brain through metabolism pathways.