外周血T细胞受体谱多样性作为结直肠癌和肺癌诊断及治疗评估的潜在生物标志物：一项前瞻性观察研究
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.
作者信息
Ma Jilong, Wang Yuanbiao, Zhang Zhixin, Cai Xinyi, Xiang Xudong, Chen Yan, Sun Fengqiong, Dong Jian
机构信息
Key Laboratory of Cell Therapy Technology Transformation Medicine of Yunnan Province, the Han Weidong Expert Workstation of Yunnan Province, Yunnan Provincial Engineering Research Centre of Cell Therapy and Quality Control System, the Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, Yunnan, China.
Department of Technology, Chengdu ExAb Biotechnology, LTD, Chengdu, Sichuan, China.
出版信息
Cancer Med. 2025 May;14(10):e70937. doi: 10.1002/cam4.70937.
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.
背景
T细胞受体（TCR）多样性50（D50）值可评估外周血（PB）TCR多样性和免疫功能。本研究旨在评估D50值在结直肠癌（CRC）和非小细胞肺癌（NSCLC）诊断及治疗评估中的潜在价值。
方法
这项前瞻性观察性研究于2021年1月至2022年6月在云南省肿瘤医院纳入了CRC患者、良性结直肠疾病（BCD）患者、NSCLC患者、良性结节对照（BNC）患者以及健康供者（HD）。采集PB样本进行TCRβ测序，并计算不同组别的D50值并进行比较。采用曲线下面积（AUC）评估D50对CRC和NSCLC的诊断性能。
结果
共纳入114名HD、115名CRC患者、31名BCD患者、67名NSCLC患者和25名BNC患者。与HD相比，CRC和NSCLC患者的D50均显著降低（p < 0.001），而BCD和BNC患者的TCR多样性略有下降（p < 0.05）。有淋巴结转移的NSCLC患者的D50明显低于无淋巴结转移的患者（0.05对0.11，p < 0.01）。癌胚抗原（CEA）水平正常的CRC和NSCLC患者的D50较高（p < 0.05）。D50值对CRC和NSCLC早期检测的潜力得到证实，CRC的受试者工作特征曲线（ROC）下面积（AUC）为0.736（敏感性：71.30%，特异性：68.42%），NSCLC为0.768（敏感性：83.58%，特异性：60.53%）。肿瘤退缩分级（TRG）为0 - 1的患者与TRG为2 - 3的患者之间的D50值存在显著差异（p = 0.027），AUC为0.731（敏感性：68.75%，特异性：76.92%）。
结论
这些发现表明，PB TCR D50值在癌症诊断和评估新辅助治疗疗效方面可能具有重要的临床价值。
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