Dataset Information

The role of PDGFRA as a therapeutic target in young colorectal cancer patients.

ABSTRACT:

Background

Young patients with colorectal cancer (CRC) exhibit poor prognoses compared to older patients due to the difficulty in early diagnosis and treatment. However, the underlying molecular characteristics are still unclear.

Methods

We conducted a comprehensive analysis of 49 CRC patients without hereditary CRC using the whole-exome and RNA sequencing with tumor and matched normal samples. A total of 594 TCGA samples and 4 patient-derived cells were utilized for validation.

Results

Consensus molecular subtype 4 (CMS4) (53.85%) and CMS2 (38.46%) were enriched in the young (≤ 40 years) and old (> 60 years) age groups, respectively. A CMS4-associated gene, platelet-derived growth factor receptor α (PDGFRA), was significantly upregulated in young patients with CRC (FC = 3.21, p = 0.0001) and was negatively correlated with age (p = 0.0001, R = - 0.526). Moreover, PDGFRA showed a positive co-expression with metastasis-related genes in young CRC patients. In vitro validation confirmed that young patient-derived cells (PDCs) showed an enriched expression of PDGFRA compared to old PDCs and a reduced proliferation rate by knockdown of PDGFRA. Furthermore, young CRC patients were more sensitive to regorafenib, a PDGFRA-targeting drug, than old CRC patients.

Conclusions

Our study suggests that CRC in young patients is associated with CMS4 and PDGFRA. In addition, PDGFRA may serve potential of novel therapeutic strategies and represent a predictive biomarker of response to regorafenib for young CRC patients.

SUBMITTER: Kim TW

PROVIDER: S-EPMC8546951 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

The role of PDGFRA as a therapeutic target in young colorectal cancer patients.

Kim Tae Won TW Hong Hye Kyung HK Lee Chung C Kim Sunmin S Lee Woo Yong WY Yun Seong Hyeon SH Kim Hee Cheol HC Huh Jung Wook JW Park Yoon Ah YA Joung Je-Gun JG Park Woong-Yang WY Cho Yong Beom YB

Journal of translational medicine 20211026 1

<h4>Background</h4>Young patients with colorectal cancer (CRC) exhibit poor prognoses compared to older patients due to the difficulty in early diagnosis and treatment. However, the underlying molecular characteristics are still unclear.<h4>Methods</h4>We conducted a comprehensive analysis of 49 CRC patients without hereditary CRC using the whole-exome and RNA sequencing with tumor and matched normal samples. A total of 594 TCGA samples and 4 patient-derived cells were utilized for validation.<h ...[more]

PMID: 34702313

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Dataset Information

The role of PDGFRA as a therapeutic target in young colorectal cancer patients.

Background

Methods

Results

Conclusions

Publications

The role of PDGFRA as a therapeutic target in young colorectal cancer patients.

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