Characterization of the T-cell receptor repertoire associated with lymph node metastasis in colorectal cancer

Ya'nan Zhen; Hong Wang; Runze Jiang; Fang Wang; Cunbao Chen; Zhongfa Xu; Ruixue Xiao

doi:10.3389/fonc.2024.1354533

Characterization of the T-cell receptor repertoire associated with lymph node metastasis in colorectal cancer

Front Oncol. 2024 Nov 12:14:1354533. doi: 10.3389/fonc.2024.1354533. eCollection 2024.

Authors

Ya'nan Zhen¹, Hong Wang¹, Runze Jiang², Fang Wang^{3

4}, Cunbao Chen^{3

4}, Zhongfa Xu^#^{2

3

4}, Ruixue Xiao^#⁵

Affiliations

¹ Department of Gastrointestinal Surgery, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China.
² Jinan Biomedical Industry Academy of Shandong First Medical University, Jinan, Shandong, China.
³ Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China.
⁴ Gastroenterology Research Institute and Clinical Center, Shandong First Medical University, Jinan, Shandong, China.
⁵ Department of Pathology, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China.

^# Contributed equally.

Abstract

Purpose: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with lymph node (LN) metastasis playing a pivotal role in disease progression. This study aimed to explore the T-cell receptor (TCR) repertoire among CRC patients, distinguishing those with LN metastasis from those without, in order to uncover potential biomarkers for predicting metastasis.

Methods: We analyzed the TCR repertoire in CRC patients with and without LN metastasis. A classification model utilizing random forest analysis was developed to assess the predictive potential of the TCR repertoire.

Results: The findings demonstrated a significant increase in the number of V-J combinations and immune CDR3 sequences in patients with LN metastasis compared to the control group. The classification model achieved high accuracy in differentiating patients with LN metastasis, with AUC values ranging from 0.514 to 0.794. Specific V-J combinations and CDR3 sequences were identified as significant predictors of the model's predictive accuracy.

Conclusion: These results suggest that the TCR repertoire is altered in CRC patients exhibiting LN metastasis, potentially influencing disease progression. This study highlights the importance of TCR repertoire analysis as a non-invasive biomarker for predicting LN metastasis in CRC patients.

Keywords: T-cell receptor repertoire; TCR sequencing; biomarkers; colorectal cancer; lymph node metastasis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Innovation Project of Shandong Academy of Medical Sciences.