Abstract
Lung squamous cell carcinoma (LUSC) is one of the leading causes of tumor-driven deaths in the world. To date, studies on the tumor heterogeneity of LUSC at genomic level have only revealed limited therapeutic benefits. Therefore, system-wide research of LUSC at proteomic level may further improve precision medicine strategies on individual demands. To this end, we performed proteomic and phosphoproteomic study for LUSC samples of 25 Chinese patients. From our results, two subgroups (Cluster I and II) based on proteomic data were identified, which were associated with distinct molecular characteristics and clinicopathologic features. Combined with phosphoproteomic data, our result showed that spliceosome pathway was enriched in Cluster I, while focal adhesion pathway, immune-related pathways and Ras signaling pathway were enriched in Cluster II. In addition, we found that lymph node metastasis (LNM) was associated with our proteomic subgroups and cell cycle pathway was enriched in patients with LNM. Further analysis showed that MCM2, a DNA replication licensing factor involved in cell cycle pathway, was highly expressed in patients with poor prognosis, which was further proved by immunohistochemistry (IHC) analysis. In summary, our study provided a resource of the proteomic and phosphoproteomic features of LUSC in Chinese patients.
Highlights
Lung cancer is the most malignant tumor with the highest morbidity and mortality in the world [1, 2]
To explore the influence of MCM2 on lung squamous cell carcinoma (LUSC), we conducted IHC analysis based on tissue microarray (TMA) including 75 cases of LUSC patients, we found that MCM2 had higher expression in LUSC with lymph node metastasis (LNM) (Figure 5C, Supplementary Table S18)
LUSC accounts for a significant percentage of Non-small cell lung cancer (NSCLC), but has limited biomarkers for diagnosis and therapy, except for a few immunotherapies targeting at PD1 and PDL1 [6,7,8]
Summary
Lung cancer is the most malignant tumor with the highest morbidity and mortality in the world [1, 2]. LUSC was identified with multiple mutations in cancer driver genes such as TP53 and PTEN [4], and four LUSC mRNA expression subtypes (primitive, classical, secretory, and basal) related with different biological processes (proliferation, xenobiotic metabolism, immune response, cell adhesion) were identified [5]. In contrast to genetic features, proteomic characteristics are more directive to reflect the pattern of LUSC as proteins are the “executioners of life” [9, 10]. A proteogenomic study on LUSC from Western patients has been conducted, which identified three proteomic subtypes associated with immune biology (inflammatory cluster), oxidation-reduction biology (redox cluster) and biology associated with Wnt/stromal signaling (mixed cluster). This study provided a resource and suggested therapeutic strategies based on metabolism and immune for LUSC in Western countries [11]
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