Peripheral Blood T-Cell Receptor Repertoire Diversity as a Potential Biomarker in the Diagnosis and Treatment Evaluation of Colorectal and Lung Cancers: A Prospective Observational Study.

Background: T-cell receptor (TCR) diversity 50 (D50) values could assess peripheral blood (PB) TCR diversity and immunity. This study aimed to evaluate the potential D50 value in the diagnosis and treatment evaluation of colorectal cancer (CRC) and nonsmall-cell lung cancer (NSCLC).

Methods: This prospective observational study enrolled patients with CRC, benign colorectal disease (BCD), NSCLC, or benign nodule controls (BNC) and healthy donors (HD) at Yunnan Cancer Hospital between January 2021 and June 2022. PB specimens were used for TCRβ sequencing, and D50 was calculated and compared within different groups. The area under the curve (AUC) was used to evaluate the diagnostic performance of D50 in CRC and NSCLC.

Results: A total of 114 HD and 115 CRC, 31 BCD, 67 NSCLC, and 25 BNC patients were enrolled. Both CRC and NSCLC patients exhibited significantly lower D50 compared with HDs (p < 0.001), whereas BCD and BNC patients showed a modest decrease in TCR diversity (p < 0.05). NSCLC patients with lymph node metastases had markedly lower D50 than those without lymph node metastasis (0.05 vs. 0.11, p < 0.01). Higher D50 was found in CRC and NSCLC patients with normal carcinoembryonic antigen (CEA) levels (p < 0.05). The potential of D50 value for early detection of CRC and NSCLC was demonstrated, with an area under the receiver operating characteristic curve (AUC) of 0.736 for CRC (sensitivity: 71.30%, specificity: 68.42%) and 0.768 for NSCLC (sensitivity: 83.58%, specificity: 60.53%). Significant differences in D50 values were observed between patients with tumor regression grade (TRG) 0-1 and those with TRG 2-3 (p = 0.027), with an AUC of 0.731 (sensitivity: 68.75%, specificity: 76.92%).

Conclusion: These findings suggest that the PB TCR D50 values may have significant clinical value in cancer diagnosis and in evaluating the efficacy of neoadjuvant therapies.