Cell: A more complete molecular picture of lung squamous cell carcinoma has appeared!

To further understand the biological basis of LSCC, a team led by researchers from the Broad Institute of MIT and Harvard University and the National Cancer Institute Clinical Proteomics Tumor Analysis Alliance (CPTAC), including from Baylor Medicine The collaborators of the institute have developed the largest and most comprehensive molecular map of LSCC to date

"Patients with lung squamous cell carcinoma have very limited treatment options, and even with limited success in understanding this disease, it may have an impact on people's lives," said Shanka Sa, head of the Proteomics Group at the Broad Institute.

Channel opportunity

In their study, the research team analyzed the DNA, RNA, protein, and post-translational protein modifications (PTMs, phosphorylation, acetylation, and ubiquitination) of 108 cases of tumor treatment before treatment, and compared them with normal tissues.

They also noticed that some patients’ tumors showed low expression of p63 but high expression of survivin, a protein that regulates cell proliferation and death, and is also the target of clinical trials for other tumor types

In addition, the team’s data suggests that tumors driven by overexpression of the transcription factor SOX2 may be susceptible to treatment with chromatin modifiers such as LSD1 and EZH2

"Proteomics and crane data help us see the functional effects of the genome," explains Michael Gillette, senior team leader in extensive proteomics, pulmonary and critical care medicine, and the attending physician at Massachusetts General Hospital, and the article The second author Steven Carr and Dr.

He added: "Often these insights imply unexplored treatment options, or specific subpopulations that may benefit from specific treatments

Immunity Exploration

Although immunotherapy represents the greatest advancement in the treatment of LSCC in recent decades, the prognosis of patients lags behind that of LUAD; only a few patients with LSCC show long-term responses

"A deeper understanding of the immune landscape of LSCC tumors may ultimately lead to more effective immunotherapy and markers for patient stratification," said Zhang, who is the director of the Leicester and Sue Smith Breast Center and Baylor Molecular and Human Genetics Professor of the department

Metabolic disorders and crosstalk

Ubiquitination is the process by which cells label proteins with another small protein called ubiquitin (or its biochemical relatives) and destroy it

A new subtype has appeared

Previous work has identified four molecular subtypes of LSCC through genomics, corresponding to different cell types and processes

Ana Robles, project director of the NCI Cancer Clinical Proteomics Research Office, said: "This is noteworthy because LSCC tumors usually lack the type of kinase alteration present in LUAD, which is the basis for the development of broad-spectrum therapeutic inhibitors

The collaborators of this research completed their work under the auspices of CPTAC, a multidisciplinary/multi-institutional effort sponsored by nci to accelerate the understanding of the molecular basis of cancer through the application of large-scale proteome analysis

Carr, Senior Director of Broad Proteomics, said: "Our research and the CPTAC network and other studies increasingly show the importance of multi-omics and comprehensive analysis of tumors in order to provide a more detailed and subtle understanding of cancer

This research was supported by the National Cancer Institute Clinical Proteomics Tumor Analysis Alliance

Journal Reference :

1. Shankha Satpathy, Karsten Krug, Pierre M.