Publications by authors named "Chunliu Zhang"

4 Publications

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Lung cancer-associated T cell repertoire as potential biomarker for early detection of stage I lung cancer.

Lung Cancer 2021 Dec 28;162:16-22. Epub 2021 Sep 28.

Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, China; Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, China; Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Changsha, China. Electronic address:

Background: Early detection of lung cancer in asymptomatic patients remains challenging, especially for stage I. Considering the substantial interaction with tumor immunogenicity, we hypothesized that lung cancer-associated TCR (LC-aTCR) may serve as potential biomarker in early detection of stage I lung cancer.

Methods: Individuals who received low-dose computed tomography (LDCT) screening were enrolled in the study. Surgical tissues and peripheral blood specimens were collected and performed with DNA-based T cell repertoire (TCR) sequencing. The motif-based algorithm was used to deconstruct specific lung cancer-associated TCRs (LC-aTCRs).

Results: A total of 146 individuals participating in the real-world LDCT screening project were enrolled in this study, including 52 patients with pathologically-confirmed stage I lung cancer and 94 non-cancer controls. We developed a motif-based algorithm to define 80 LC-aTCRs in the training cohort. Moreover, in the validation cohort, high sensitivity and specificity was showed in stage I lung cancer with 72% and 91% respectively, and the AUC of the ROC curve was 0.91 (95% CI: 0.85 ∼ 0.96).

Conclusion: This work provides inspiration for stage I lung cancer detection by using blood TCR profiling data. The combination of TCR-based assay and routine screening deserves further testing in larger cohorts.
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December 2021

Multiomics Analysis Reveals Distinct Immunogenomic Features of Lung Cancer with Ground-Glass Opacity.

Am J Respir Crit Care Med 2021 11;204(10):1180-1192

Department of Thoracic Surgery and.

Ground-glass opacity (GGO)-associated lung cancers are common and radiologically distinct clinical entities known to have an indolent clinical course and superior survival, implying a unique underlying biology. However, the molecular and immune characteristics of GGO-associated lung nodules have not been systemically studied. To provide mechanistic insights for the treatment of these radiologically distinct clinical entities. We initiated a prospective cohort study to collect and characterize pulmonary nodules with GGO components (nonsolid and part-solid nodules) or without GGO components, as precisely quantified by using three-dimensional image reconstruction to delineate the molecular and immune features associated with GGO. Multiomics assessment conducted by using targeted gene panel sequencing, RNA sequencing, TCR (T-cell receptor) sequencing, and circulating tumor DNA detection was performed. GGO-associated lung cancers exhibited a lower tumor mutation burden than solid nodules. Transcriptomic analysis revealed a less active immune environment in GGO components and immune pathways, decreased expression of immune activation markers, and less infiltration of most immune-cell subsets, which was confirmed by using multiplex immunofluorescence. Furthermore, T-cell repertoire sequencing revealed lower T-cell expansion in GGO-associated lung cancers. HLA loss of heterozygosity was significantly less common in lung adenocarcinomas with GGO components than in those without. Circulating tumor DNA analysis suggested that the release of tumor DNA to the peripheral blood was correlated with the tumor size of non-GGO components. Compared with lung cancers presenting with solid lung nodules, GGO-associated lung cancers are characterized by a less active metabolism and a less active immune microenvironment, which may be the mechanisms underlying their indolent clinical course. Clinical trial registered with (NCT03320044).
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November 2021

Circulating tumor DNA by high-throughput sequencing of T cell receptor monitored treatment response and predicted treatment failure in T cell lymphomas.

Int J Lab Hematol 2021 Oct 18;43(5):1041-1049. Epub 2021 Mar 18.

Department of Hematology, Peking Union Medical College Hospital, Beijing, China.

Introduction: Next-generation sequencing (NGS)-based circulating tumor DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. Studies for T cell lymphoma are limited.

Methods: We explored whether this technology is applicable to T cell lymphoma with different subtypes and assessed its performance in clinical settings.

Results: Thirty tumor and 74 blood samples were analyzed in our study. Malignant clone was identified in 23 of the 30 (76.7%) tumor samples through high-throughput sequencing (HTS) combined with PCR. We detected the same tumor clone in plasma in 18out of the 23 (78.3%) patients. Circulating tumor DNA fraction correlated with lactate dehydrogenase (LDH) (r = .52, P = .017), high level of ctDNA predicted treatment failure (P = .0003) and there was a trend patients with high ctDNA burden would have poorer PFS Furthermore, ctDNA changed in concordance with clinical outcome and was more sensitive than PET/CT. Also, recurrence of ctDNA was an important clue for relapse.

Conclusion: In conclusion, our study indicated that ctDNA monitoring was suitable for T cell lymphoma. High level of pretreatment ctDNA was a poor prognosis factor and changes of ctDNA correlated well with clinical courses and was sensitive to find early relapse.
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October 2021

TCR-Seq Identifies Distinct Repertoires of Distant-Metastatic and Nondistant-Metastatic Thyroid Tumors.

J Clin Endocrinol Metab 2020 09;105(9)

Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang Province, China.

Context: Malignant thyroid tumor with distant metastasis is associated with poor outcome. Early detection of distant metastasis is of great clinical importance.

Objective: Thyroid tumor infiltrated with T cells can serve as a biomarker for monitoring metastasis.

Design: A retrospective analysis was performed of patient clinical samples collected between 2012 to 2018, using T-cell receptor sequencing (TCR-seq) for clinical exploration.

Setting: This study took place at Zhejiang Cancer Hospital.

Patients: Sixty-eight patients with papillary thyroid cancer (PTC) (distinct metastatic status) and 21 patients with benign nodules were enrolled. All patients had not received any treatment before surgery.

Main Outcome Measure: The characteristics of TCRβ complementary-determining region 3 (CDR3) for each patient were determined by high-throughput sequencing.

Results: The TCRβ diversity of malignant tumors is significantly higher than benign nodules both in blood and tumor samples (Shannon index, blood, P < .01; tumor, P < .001). The malignant tumors with distant metastasis or invasiveness showed lower TCRβ diversity than nonmetastasis (Shannon index, P < .01) or noninvasive (Shannon index, P < .01) malignant tumors. Analysis of the Morisita-Horn similarity index indicated significant TCRβ repertoire similarity between tumor and blood in distant-metastatic patients (comparison with nonmetastasis, P < .05). According to the discrepancy of the CDR3 among patients with different clinicopathological status, the classifier was constructed to discriminate distant-metastatic individuals. A promising area under the curve value of 83.8% was obtained with the number of overlapping CDR3 clonotypes.

Conclusion: The availability and reliability of TCR-seq render it prospective to translate these intrinsic attributes into clinical practice for monitoring distant metastasis in PTC patients.
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September 2020