Browsing by Author "Cheng, Qing"

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    An age-independent gene signature for monitoring acute rejection in kidney transplantation.
    (Theranostics, 2020-01) Shaw, Brian I; Cheng, Daniel K; Acharya, Chaitanya R; Ettenger, Robert B; Lyerly, Herbert Kim; Cheng, Qing; Kirk, Allan D; Chambers, Eileen T
    Acute rejection (AR) remains a significant problem that negatively impacts long-term renal allograft survival. Numerous therapies are used to prevent AR that differ by center and recipient age. This variability confounds diagnostic methods. Methods: To develop an age-independent gene signature for AR effective across a broad array of immunosuppressive regimens, we compiled kidney transplant biopsy (n=1091) and peripheral blood (n=392) gene expression profiles from 12 independent public datasets. After removing genes differentially expressed in pediatric and adult patients, we compared gene expression profiles from biopsy and peripheral blood samples of patients with AR to those who were stable (STA), using Mann-Whitney U Tests with validation in independent testing datasets. We confirmed this signature in pediatric and adult patients (42 AR and 47 STA) from our institutional biorepository. Results: We identified a novel age-independent gene network that identified AR from both kidney and blood samples. We developed a 90-probe set signature targeting 76 genes that differentiated AR from STA and found an 8 gene subset (DIP2C, ENOSF1, FBXO21, KCTD6, PDXDC1, REXO2, HLA-E, and RAB31) that was associated with AR. Conclusion: We used publicly available datasets to create a gene signature of AR that identified AR irrespective of immunosuppression regimen or recipient age. This study highlights a novel model to screen and validate biomarkers across multiple treatment regimens.
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    Pre-existing Castration-resistant Prostate Cancer-like Cells in Primary Prostate Cancer Promote Resistance to Hormonal Therapy.
    (European urology, 2022-01-17) Cheng, Qing; Butler, William; Zhou, Yinglu; Zhang, Hong; Tang, Lu; Perkinson, Kathryn; Chen, Xufeng; Jiang, Xiaoyin Sara; McCall, Shannon J; Inman, Brant A; Huang, Jiaoti

    Background

    Hormonal therapy targeting the androgen receptor inhibits prostate cancer (PCa), but the tumor eventually recurs as castration-resistant prostate cancer (CRPC).

    Objective

    To understand the mechanisms by which subclones within early PCa develop into CRPC.

    Design, setting, and participants

    We isolated epithelial cells from fresh human PCa cases, including primary adenocarcinoma, locally recurrent CRPC, and metastatic CRPC, and utilized single-cell RNA sequencing to identify subpopulations destined to become either CRPC-adeno or small cell neuroendocrine carcinoma (SCNC).

    Outcome measurements and statistical analysis

    We revealed dynamic transcriptional reprogramming that promotes disease progression among 23226 epithelial cells using single-cell RNA sequencing, and validated subset-specific progression using immunohistochemistry and large cohorts of publically available genomic data.

    Results and limitations

    We identified a small fraction of highly plastic CRPC-like cells in hormone-naïve early PCa and demonstrated its correlation with biochemical recurrence and distant metastasis, independent of clinical characteristics. We show that progression toward castration resistance was initiated from subtype-specific lineage plasticity and clonal expansion of pre-existing neuroendocrine and CRPC-like cells in early PCa.

    Conclusions

    CRPC-like cells are present early in the development of PCa and are not exclusively the result of acquired evolutionary selection during androgen deprivation therapy. The lethal CRPC and SCNC phenotypes should be targeted earlier in the disease course of patients with PCa.

    Patient summary

    Here, we report the presence of pre-existing castration-resistant prostate cancer (CRPC)-like cells in primary prostate cancer, which represents a novel castration-resistant mechanism different from the adaptation mechanism after androgen deprivation therapy (ADT). Patients whose tumors harbor increased pre-existing neuroendocrine and CRPC-like cells may become rapidly resistant to ADT and may require aggressive early intervention.