Genetic differences between lung metastases and liver metastases from left-sided microsatellite stable colorectal cancer: next generation sequencing and clinical implications.

BACKGROUND

Data regarding the clinical characteristics and outcomes of lung metastases (LuM) from colorectal cancer (CRC) are different from those of liver metastases (LiM) from CRC. However, little is known about the genetic features of LuM. This study aimed to identify the different genetic characteristics of LuM and LiM from left-sided microsatellite stable CRC.

METHODS

Tissue samples of the primary tumors and paired metastases from 18 CRC patients with isolated LuM (LuM cohort), 18 patients with isolated LiM (LiM cohort), and 10 locally advanced CRC patients without metastases (control cohort) were selected for next-generation sequencing. Patients in the LiM cohort had matched clinicopathological characteristics with the LuM cohort. The single-nucleotide variations (SNVs), copy number variations (CNVs), pathway alterations, and tumor mutation burdens (TMBs) were also calculated and analyzed.

RESULTS

The CNV results showed that , and amplifications were more common in the metastatic cohorts than in the control cohort, while and amplifications were common in the controls. The LuM cohort had significantly higher proportions of , and amplification. The LuM, LiM, and control cohorts were successfully separated using pathway alteration analysis. The LuM cohort had more frequent alterations in the RTK/RAS pathway, HIPPO pathway, , and than the LiM group. The LuM cohort also had relatively higher TMBs than the LiM cohort.

CONCLUSIONS

CNVs in primary tumors could identify patients with LuM. Targeting the HIPPO pathway or and immune checkpoint inhibitors (ICIs) combined with other agents might be novel therapies for LuM.