Purpose
We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data.
Materials and Methods
The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in
EGFR
,
ALK
,
BRAF
,
KRAS
,
TP53
, and the wild-type.
Results
Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged:
KRAS
,
TP53
, and
EGFR
+
TP53
mutations (MC1); and
EGFR
,
BRAF
, and
ALK
mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of
TNF
,
IL1B
, and chemokines linked to alternative immune pathways. Remarkably, co-occurring
EGFR
and
TP53
mutations were grouped as MC1.
EGFR
+
TP53
mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to
EGFR
mutations. In T/NK cells,
EGFR
+
TP53
mutations showed a higher expression of features related to cell activity and differentiation, whereas
EGFR
mutations showed the opposite.
Conclusion
Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.