Identification of CircRNA signature associated with tumor immune infiltration to predict therapeutic efficacy of immunotherapy

Yu, Dong; Gao, Qian; Chen, Yong; Zhang, Zhao; Du, Yanhua; Liu, Yuan; Zhang, Guanxiong; Li, Shengli; Wang, Gaoyang; Chen, Xiang; Li, Hong; Han, Leng; Ye, Youqiong

doi:10.1038/s41467-023-38232-y

Cited by 30 publications

(16 citation statements)

References 85 publications

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“…In the study conducted by Dong et al . [13], it was observed in metastatic melanoma patients from the Gide et al . cohort [54] and independently validated in metastatic melanoma patients from the Berger et al .…”

Section: Resultsmentioning

confidence: 99%

“…CIRIquant [72], find_circ [73], and circRNA_finder [74]. This approach is akin to the one utilized in the study conducted by Dong et al [13] (refer to the Methods section for more details). In total, we detected 793,316 circRNAs using at least two circRNA detection methods.…”

Section: Data Summary Of Tcciamentioning

confidence: 99%

“…In the study conducted by Dong et al [13], it was observed in metastatic melanoma patients from the Gide et al cohort [54] and independently validated in metastatic melanoma patients from the Berger et al cohort [63], who exhibited high expression of circTMTC3, experienced poorer survival outcomes and demonstrated reduced treatment responsiveness compared to those with low circTMTC3 expression. To illustrate the functionality of the TCCIA, here, we performed a reproducible analysis on the same cohorts (Figure 4).…”

Section: Case Studies Validating and Extending Data Of Two Reported C...mentioning

confidence: 99%

“…Consistent with the survival outcome, we observed that TMTC3:+:chr12:88148287:88176319 was the only isoform of circTMTC3 to exhibit significant upregulation in non-responding patients from both metastatic melanoma cohorts (Figure 4F-G). Mechanistically, Dong et al [13] demonstrated that the overexpression of circTMTC3 could elevate PD-L1 expression through the miR-142-5p/PD-L1 axis, thereby reducing T cell activity and promoting immune evasion. Our identification of the specific functional isoform of circTMTC3 may stimulate further investigation into the dynamics and role of circRNA isoforms in immuno-oncology.…”

Section: Case Studies Validating and Extending Data Of Two Reported C...mentioning

confidence: 99%

“…In cancer, circRNAs have been implicated in proliferation, metastasis, and malignancy hallmarks [11]. Moreover, circRNAs are now recognized as critical regulators and potential biomarker of tumor immunity and immunotherapy response [7,12,13]. Accumulating evidence indicates circRNAs modulate TME and immunotherapy outcomes through various mechanisms in cancers like lung cancer, melanoma, colorectal cancer, and pancreatic cancer [14,15].…”

Section: Introductionmentioning

confidence: 99%

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TCCIA: A Comprehensive Resource for Exploring CircRNA in Cancer Immunotherapy

Wang,

Xiong,

Zhang

et al. 2023

Preprint

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Background: Immunotherapies targeting immune checkpoints have gained increasing attention in cancer treatment, emphasizing the need for predictive biomarkers. Circular RNAs (circRNAs) have emerged as critical regulators of tumor immunity, particularly in the PD-1/PD-L1 pathway, and have shown potential in predicting the efficacy of immunotherapies. However, the precise roles of circRNAs in cancer immunotherapy remain incompletely understood. While existing databases focus on either circRNA profiles or immunotherapy cohorts, there is currently no platform that enables the exploration of the intricate interplay between circRNAs and anti-tumor immunotherapy. Therefore, the development of a comprehensive resource that integrates circRNA profiles, immunotherapy response data, and clinical benefits is crucial for advancing our understanding of circRNA-mediated tumor-immune interactions and developing effective immunotherapy biomarkers. Methods: To address these gaps, we constructed the Cancer CircRNA Immunome Atlas (TCCIA), the first database that combines circRNA profiles, immunotherapy response data, and clinical outcomes across multi-cancer types. The construction of TCCIA involved applying standardized preprocessing to the raw sequencing FASTQ files, characterizing circRNA profiles using CIRCexplorer2, analyzing tumor immunophenotypes through IOBR, and compiling immunotherapy response data from diverse cohorts treated with immune-checkpoint blockades (ICBs). Results: TCCIA encompasses over 3,700 clinical samples obtained from 18 cohorts treated with ICBs, including PD-1/PD-L1 and CTLA-4 inhibitors, along with other treatment modalities. The database provides researchers and clinicians with a cloud-based platform that enables interactive exploration of circRNA data in the context of ICB. The platform offers a range of analytical tools, including visualization of circRNA abundance and correlation, association analysis between circRNAs and clinical variables, assessment of the tumor immune microenvironment, exploration of tumor molecular signatures, evaluation of treatment response or prognosis, and identification of altered circRNAs in immunotherapy-sensitive and resistant tumors. To illustrate the utility of TCCIA, we performed a re-analysis on a melanoma cohort with TCCIA, and found that an isoform of circTMTC3, TMTC3:+:chr12:88148287:88176319, played a significant role in predicting unfavorable survival outcomes and treatment nonresponse. Conclusions: TCCIA represents a significant advancement over existing resources, providing a comprehensive platform to investigate the role of circRNAs in immune oncology.

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Section: Resultsmentioning

confidence: 99%

Section: Data Summary Of Tcciamentioning

confidence: 99%

Section: Case Studies Validating and Extending Data Of Two Reported C...mentioning

confidence: 99%

Section: Case Studies Validating and Extending Data Of Two Reported C...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TCCIA: A Comprehensive Resource for Exploring CircRNA in Cancer Immunotherapy

Wang,

Xiong,

Zhang

et al. 2023

Preprint

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Hypoxic Exosomal circPLEKHM1‐Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis

Wang,

Jin

et al. 2024

Advanced Science

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Intercellular communication often relies on exosomes as messengers and is critical for cancer metastasis in hypoxic tumor microenvironment. Some circular RNAs (circRNAs) are enriched in cancer cell‐derived exosomes, but little is known about their ability to regulate intercellular communication and cancer metastasis. Here, by systematically analyzing exosomes secreted by non‐small cell lung cancer (NSCLC) cells, a hypoxia‐induced exosomal circPLEKHM1 is identified that drives NSCLC metastasis through polarizing macrophages toward to M2 type. Mechanistically, exosomal circPLEKHM1 promoted PABPC1‐eIF4G interaction to facilitate the translation of the oncostatin M receptor (OSMR), thereby promoting macrophage polarization for cancer metastasis. Importantly, circPLEKHM1‐targeted therapy significantly reduces NSCLC metastasis in vivo. circPLEKHM1 serves as a prognostic biomarker for metastasis and poor survival in NSCLC patients. This study unveils a new circRNA‐mediated mechanism underlying how cancer cells crosstalk with macrophages within the hypoxic tumor microenvironment to promote metastasis, highlighting the importance of exosomal circPLEKHM1 as a prognostic biomarker and therapeutic target for lung cancer metastasis.

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High‐Performance Cooperative DNA Nanodevice Enables Sensitive Circular RNA Imaging and Precise Tumor Growth Suppression

Zhang,

Chen,

Luo

et al. 2024

Small Structures

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The utility of circular RNAs (circRNAs) as emerging biomarkers and regulatory factors in medical diagnostics and therapeutics is hampered by the challenges associated with their sensitive detection and precise modulation. Herein, a high‐performance cooperative DNA nanodevice (HCDN) based on DNA tetrahedron‐confined catalytic DNA assembly reaction (DT‐CDA) that enables both imaging and regulation of circRNAs is developed. Activation of the DT‐CDA is contingent upon the presence of the target circRNA, which, together with a replicative fuel probe, catalyzes the sequential opening of additional DT‐CDAs. This cooperative exponential signal amplification with negligible background interference allows HCDN to effectively detect minute quantities of circRNAs. Employing circSATB2 as a model, the HCDN demonstrates substantial downregulation of Cyclin D1 (CCND1) mRNA and protein levels in cellular and in vivo models, thereby inhibiting tumor growth. The innovative design of HCDN sets the stage for a powerful methodology conducive to enhanced clinical diagnostics and biomolecule manipulation, thereby advancing the capabilities and applications of DNA nanotechnology.

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Identification of CircRNA signature associated with tumor immune infiltration to predict therapeutic efficacy of immunotherapy

Cited by 30 publications

References 85 publications

TCCIA: A Comprehensive Resource for Exploring CircRNA in Cancer Immunotherapy

TCCIA: A Comprehensive Resource for Exploring CircRNA in Cancer Immunotherapy

Hypoxic Exosomal circPLEKHM1‐Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis

High‐Performance Cooperative DNA Nanodevice Enables Sensitive Circular RNA Imaging and Precise Tumor Growth Suppression

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