TMB detection from primary and metastatic lesions should be considered
separately: a pan-cancer study.
Background: In this study, we evaluated the difference in the tumor
mutational burden (TMB) score between primary and metastatic lesions in
pan-cancer and the different cut-offs for guiding immune checkpoint
inhibitors (ICIs) prognosis. Methods: We screened 1661 pan-cancer cases
from the cBioPortal database. The Kaplan-Meier method was applied to
obtain survival curves that were compared using the log-rank test. The
X-tile model was used to determine the optimal cut-off values of TMB.
Results: Our results showed that the tissues obtained from the
metastatic lesions had more co-occurring gene mutations than the primary
lesions (P<0.05, Q<0.05). Moreover, tissues from
patients with metastatic lesions had a higher TMB score than those from
patients with primary lesions (P = 0.024). According to the median
cut-off values of TMB from the primary and metastatic lesions, we
analyzed the overall survival (OS) in the low TMB and high TMB groups,
respectively. The results showed different OS for the two TMB groups in
primary and metastatic lesions. Subsequently, we analyzed the optimal
cut-off values of TMB score to predict survival in primary and
metastatic lesions based on the X-tile model. The optimal cut-off value
for the test tissue from primary lesions was 20.19 (P<0.001).
Importantly, the optimal cut-off value for test tissue from metastatic
lesions was 10.18 (P < 0.001). Conclusion: TMB detection from
primary and metastatic lesions should be considered separately to
predict survival for ICIs treatment.