Genomic Landscape of Metastatic Lymph Nodes and Primary Tumors in Non-Small-Cell Lung Cancer

Abstract

Objective: To investigate the genetic mutation characteristics of non-small cell lung cancers (NSCLC) with and without lymph node metastasis.Methods: Primary lesions and metastatic lymph node lesions of 36 Chinese NSCLC patients were tested for somatic mutations, tumor mutation burden, phylogenetic and clonal evolutional analysis using a 1021-gene panel by next-generation sequencing (NGS) with an average sequencing depth of 671X.Results: In this study, eighteen patients with lung adenocarcinoma (LUAD) and 18 with lung squamous cell carcinoma (LUSC) were included. Different groups had distinct characteristics of gene mutations. CTNNB1 gene mutations were only present in Nome_LC LUAD patients (p < 0.05). ARID1A mutation was however the only gene with significant alterations (p < 0.05) in Nome_LC in LUSC. Phylogenetic trees of mutated genes were also constructed. Linear and parallel evolutions of metastatic lymph nodes were observed both in LUAD and LUSC.Conclusion: LUSC exhibited more genetic mutations than LUAD. Intriguingly, there was significant difference in gene mutations between Meta_LC and Nome_LC. CTNNB1 gene alteration was the key mutation in LUAD that seems to promote proliferation of the tumor and then determine T stage. On the other hand, proliferation of the tumor was characterized by ARID1A missense mutation in LUSC, thus influencing the T stage as well. Lymph node metastasis could display both linear and parallel evolutionary characteristics in NSCLC. Different metastatic lymph nodes might have exactly the same or different mutated genes, underlining the heterogeneous genomic characteristics of these cancer types.

Immunohistochemistry combined with NGS to assist the differential diagnosis of multiple primary lung cancer with lymph node metastasis: a case report

“…There are very few mutated genes in metastatic lymph nodes, which may only be related to metastasis of the primary lesion. The mutated genes in the metastatic lymph nodes are similar to those in the corresponding primary tumor, indicating the clonal evolution of the tumor ( 15 ). Here, we report a rare case of two primary adenocarcinomas of lung lesions, with 10 groups of lymph node metastases.…”

Microsatellite instability-related prognostic risk score (MSI-pRS) defines a subset of lung squamous cell carcinoma (LUSC) patients with genomic instability and poor clinical outcome

“…The MSI status was determined by the expression data of the MMR proteins in the following process: (Santos and Rodriguez, 2022) the relative MSI status in the TCGA-LUSC cohort was identified by consensus clustering using k-means as the base method (Chen et al, 2022). The MSI score of each sample was calculated by GSVA, according to MMR proteins.…”

“…Immune checkpoint inhibitor (ICI)-based combination regimens have been moved into the first-line option, which led to a landmark change in the treatment of LUSC (Santos and Rodriguez, 2022). In contrast to LUAD, for smoking or other chemical exposures, the molecular profile of all LUSC stages is characterized by highly heterogeneous malignancy, with high genomic instability contributing to the high tumor mutational burden (Heist et al, 2012;Chen et al, 2022).…”

Integrative genomic profiling reveals characteristics of lymph node metastasis in small cell lung cancer

“…A large number of studies have found that some novel differentially expressed genes (DEGs) are closely related to LNM in lung cancer, including SCLC (9)(10)(11). Recently, Chen et al explored the characteristics of gene mutations in non-small cell lung cancer (NSCLC) with and without LNM (12). However, research into the genomic landscape or multi-omics of SCLC with various LNM statuses is limited.…”