Professor Kwang-Pyo Kim’s Research Team Identifies Chromosomal Instability and Tumor Microenvironment Patterns in NSCLC through Multi-Omics Analysis
Study published in Nature Communications reveals new molecular subtypes of non-small cell lung cancer (NSCLC)
A research team led by Professor Kwang-Pyo Kim of the Department of Applied Chemistry at Kyung Hee University has identified key molecular mechanisms related to chromosomal instability and the tumor microenvironment in non-small cell lung cancer (NSCLC), the most common type of lung cancer. Their groundbreaking findings were published in the November issue of the prestigious journal Nature Communications (IF = 14.7).
Lung cancer remains the leading cause of cancer-related deaths in Korea, accounting for approximately 21% of all cancer fatalities in 2023, with NSCLC comprising about 85% of all lung cancer cases. Due to its heterogeneous nature, establishing effective, personalized treatment strategies for NSCLC has been a major clinical challenge. Traditional classifications based solely on histological features often fall short in guiding precision medicine approaches.
Discovering Five Novel Molecular Subtypes of NSCLC
In collaboration with the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the International Cancer Proteogenome Consortium (ICPC), Professor Kim’s team analyzed multi-omics data from 691 NSCLC patients collected from Korea and international partner institutions. Kyung Hee University has been a formal member of these global consortia since signing a partnership with the U.S. National Cancer Institute in 2021.
Through comprehensive multi-omics analysis—including genomic, transcriptomic, and proteomic data—the team identified five novel molecular subtypes of NSCLC that go beyond traditional classifications. Among these:
- Subtype 4 displayed aggressive invasion and high metastatic potential, correlating with poor prognosis.
- Subtype 5 showed elevated immune activity and a strong response to adjuvant therapies.
- Subtype 3, frequently observed in squamous cell carcinoma, exhibited whole genome doubling (WGD) and high chromosomal instability, with overexpression of the XPO1 protein, indicating high proliferative capacity.
In preclinical validation, the team found that Selinexor, an XPO1 inhibitor, was highly effective in treating subtype 3. However, subtype 1, mainly found in adenocarcinoma patients, showed minimal response to the same drug, highlighting the importance of subtype-specific treatment strategies.
Toward Precision Oncology and Personalized Treatment
“This study demonstrates how multi-omics-based molecular classification can complement traditional histopathology, paving the way for more precise, personalized cancer treatment,” said Professor Kim.
Building on this research, his team plans to integrate long-read sequencing technologies with high-resolution mass spectrometry to investigate protein isoforms and further refine treatment approaches. The project is supported by the Korea Research Foundation under the Omics-Based Precision Medicine Technology Development Program.
These findings represent a major step forward in understanding the complexity of NSCLC and advancing global efforts in precision oncology.
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