Nat. Commun Hou Yingyong/Ding Chen/He Fuchu team collaborated to release a proteomic map of squamous cell carcinoma in Chinese population, revealing molecular differences between squamous cell carcinoma and adenocarcinoma

Introduction

Squamous cell carcinomas (SCCs) and adenocarcinomas (ACs) are the two most common histological subtypes of human solid cancers.

Cancer Genome Atlas (TCGA) studies have generated comprehensive molecular maps including somatic mutations, copy number alterations, DNA methylation, transcriptome, and mor.

In addition, transcriptome profiling has also identified active signaling pathways in cancer patients, but since regulation at the transcriptome level does not reflect functional effects as true as proteins, targeted therapies targeting these pathways have been largely unsuccessfu.

Recently, Hou Yingyong's team from Zhongshan Hospital Affiliated to Fudan University, Ding Chen's team from Fudan University's Human Phenotype Research Institute and He Fuchu's team from Beijing Institute of Life Sciences jointly published a paper entitled "Proteomic analysis reveals key differences between squamous cell carcinomas and adenocarcinomas" in Nature Communications across multiple tissues" articl.

Article published in Nature Communications

Main research content

Proteomic analysis of squamous cell carcinoma

A total of 333 primary tumor samples from untreated Chinese patients with SCCs, including 10 common SCCs loci, were included in the stud.

The research team screened out SCC regions with >80% tumor cells and performed proteomic analysis on the.

Proteomic data for some of these key molecules are consistent with previous genomics studie.

FigureSchematic and overall overview of proteomic analysis of SCC.

Comparison of proteomic features of SCCs and ACs

To analyze and compare functional differences between SSCs and ACs, the research team compared 333 SSCs with an independent cohort of ACs consisting of 69 patients with ACs including breast, thyroid, lung, stomach, pancreas, gallbladder and colo.

To explore the proteome coverage of SCCs and ACs, the research team performed a pairwise comparison of the proteomes between SCCs and ACs at different sites and found that 643 proteins were overexpressed in ACs and 895 proteins were overexpressed in SCC.

To further elucidate the underlying mechanisms of the differences between ACs and SCCs, the research team used the GENEMINIA tool to predict the interactions of kinases and transcription factors (TFs) that might target these differential proteins, and found that ACs involved in extracellular matrix and glucose metabolism were enriched in AC.

FigureComparative analysis of proteomic features of SCCs and AC.

Proteome-based hierarchical clustering of SCCs

Previous studies have shown that SCCs can be clustered into subgroups based on genomic and transcriptomic information, but proteome-based clustering studies are still lackin.

In addition, the research team also analyzed all the differential proteins of the 4 subtypes and found two proteins with prognostic valu.

FigureProteome-based hierarchical clustering of squamous cell carcinom.

Construction and performance evaluation of tumor type classifiers

Effective management of SCCs should include reliable biomarkers and rationally designed preventive and therapeutic drug.

Considering that these proteomic markers may have averaged signals from different cell populations, the research team examined the spatial distribution of 3 biomarkers PRKCE, SL27A1 and CPXM2 at the tissue level by performing immunohistochemistry on serial sections of patients in the SCCs cohor.
expres.
 

FigureConstruction and performance evaluation and validation of tumor type classifier.
Source: Nature Communications

Epilogue

Taken together, comprehensive genomic and transcriptomic analysis of pan-SCCs broadens our understanding of the molecular events associated with this malignanc.
The research team revealed the common and specific characteristics of SCCs in the Chinese population through in-depth proteomic analysis, and then gained a deeper understanding of the clinical, biological and therapeutic aspects of SCC.
In addition, proteomic profiling of SCCs and ACs samples revealed differentially activated key signaling pathways, clinically and therapeutically relevant subgroups,et.
This study uses a proteomic platform to conduct a systematic and comprehensive analysis of pan-SCCs, and these results can serve the scientific community as a resource for clinical proteomic data, which has important implications for better understanding of SCC.

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