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Original Articles
- Genitourinary cancer
- Favorable Immunotherapy Plus Tyrosine Kinase Inhibition Outcome of Renal Cell Carcinoma Patients with Low CDK5 Expression
- Xianglai Xu, Ying Wang, Zhaoyi Chen, Yanjun Zhu, Jiajun Wang, Jianming Guo
- Cancer Res Treat. 2023;55(4):1321-1336. Published online April 3, 2023
- DOI: https://doi.org/10.4143/crt.2022.1532
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Abstract
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Supplementary Material
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ePub - Purpose
Immunotherapy (IO) plus tyrosine kinase inhibitor (TKI) has become the first-line treatment for advanced renal cell carcinoma, despite the lack of prognostic biomarkers. Cyclin-dependent kinase 5 (CDK5) affects the tumor microenvironment, which may influence the efficacy of TKI+IO.
Materials and Methods
Two cohorts from our center (Zhongshan Metastatic Renal Cell Carcinoma [ZS-MRCC] cohort, Zhongshan High-risk Localized Renal Cell Carcinoma [ZS-HRRCC] cohort) and one cohort from a clinical trial (JAVELIN-101) were enrolled. The expression of CDK5 of each sample was determined by RNA sequencing. Immune infiltration and T cell function were evaluated by flow cytometry and immunohistochemistry. Response and progression-free survival (PFS) were set as primary endpoints.
Results
Patients of low CDK5 expression showed higher objective response rate (60.0% vs. 23.3%) and longer PFS in both cohorts (ZS-MRCC cohort, p=0.014; JAVELIN-101 cohort, p=0.040). CDK5 expression was enhanced in non-responders (p < 0.05). In the ZS-HRRCC cohort, CDK5 was associated with decreased tumor-infiltrating CD8+ T cells, which was proved by immunohistochemistry (p < 0.05) and flow cytometry (Spearman’s ρ=–0.49, p < 0.001). In the high CDK5 subgroup, CD8+ T cells revealed a dysfunction phenotype with decreased granzyme B, and more regulatory T cells were identified. A predictive score was further constructed by random forest, involving CDK5 and T cell exhaustion features. The RFscore was also validated in both cohorts. By utilizing the model, more patients might be distinguished from the overall cohort. Additionally, only in the low RFscore did TKI+IO outperform TKI monotherapy.
Conclusion
High-CDK5 expression was associated with immunosuppression and TKI+IO resistance. RFscore based on CDK5 may be utilized as a biomarker to determine the optimal treatment strategy. -
Citations
Citations to this article as recorded by
- SPP1 expression indicates outcome of immunotherapy plus tyrosine kinase inhibition in advanced renal cell carcinoma
Xianglai Xu, Jinglai Lin, Jiahao Wang, Ying Wang, Yanjun Zhu, Jiajun Wang, Jianming Guo
Human Vaccines & Immunotherapeutics.2024;[Epub] CrossRef - Efficacy and Safety of Immuno-Oncology Plus Tyrosine Kinase Inhibitors as Late-Line Combination Therapy for Patients with Advanced Renal Cell Carcinoma
Shuzo Hamamoto, Yoshihiko Tasaki, Toshiharu Morikawa, Taku Naiki, Toshiki Etani, Kazumi Taguchi, Shoichiro Iwatsuki, Rei Unno, Tomoki Takeda, Takashi Nagai, Kengo Kawase, Yoshihisa Mimura, Yosuke Sugiyama, Atsushi Okada, Yoko Furukawa-Hibi, Takahiro Yasui
Journal of Clinical Medicine.2024; 13(12): 3365. CrossRef - PSMD2 overexpression as a biomarker for resistance and prognosis in renal cell carcinoma treated with immune checkpoint and tyrosine kinase inhibitors
Xianglai Xu, Jiahao Wang, Ying Wang, Yanjun Zhu, Jiajun Wang, Jianming Guo
Cellular Oncology.2024; 47(5): 1943. CrossRef - External validation of hemoglobin and neutrophil levels as predictors of the effectiveness of ipilimumab plus nivolumab for treating renal cell carcinoma
Shuzo Hamamoto, Yoshihiko Tasaki, Shimpei Yamashita, Junya Furukawa, Kazutoshi Fujita, Ryotaro Tomida, Makito Miyake, Noriyuki Ito, Hideto Iwamoto, Yosuke Sugiyama, Kazumi Taguchi, Takahiro Yasui
Frontiers in Oncology.2024;[Epub] CrossRef
- SPP1 expression indicates outcome of immunotherapy plus tyrosine kinase inhibition in advanced renal cell carcinoma
- 3,426 View
- 190 Download
- 5 Web of Science
- 4 Crossref
- Breast cancer
- Clinical Evidence of Chemotherapy or Endocrine Therapy Maintenance in Patients with Metastatic Breast Cancer: Meta-Analysis of Randomized Clinical Trials and Propensity Score Matching of Multicenter Cohort Study
- Wei Ren, Yunfang Yu, Huangming Hong, Ying Wang, Quanlong Gao, Yongjian Chen, Peixian Chen, Jianli Zhao, Qiyun Ou, Dagui Lin, Tuping Fu, Yujie Tan, Chenchen Li, Xinxin Xie, Guolin Ye, Jun Tang, Herui Yao
- Cancer Res Treat. 2022;54(4):1038-1052. Published online February 4, 2022
- DOI: https://doi.org/10.4143/crt.2021.698
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in metastatic breast cancer (MBC) patients.
Materials and Methods
The meta-analysis of randomized clinical trials (RCTs) and propensity score matching of multicenter cohort study evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. This study is registered with PROSPERO: CRD42017071858 and ClinicalTrials.gov: NCT04258163.
Results
A total of 2,867 patients from 15 RCTs and 760 patients from multicenter cohort were included. The results from meta-analysis showed that chemotherapy maintenance improved progression-free survival (PFS) (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.54 to 0.73; p < 0.001; moderate-quality evidence) and overall survival (OS) (HR, 0.87; 95% CI 0.78 to 0.97; p=0.016; high-quality evidence) than observation. In the cohort study, for hormone receptor–positive MBC patients, chemotherapy maintenance improved PFS (HR, 0.67; 95% CI, 0.52 to 0.85; p < 0.001) and OS (HR, 0.55; 95% CI 0.42 to 0.73; p < 0.001) compared with observation, and endocrine therapy maintenance also improved PFS (HR, 0.65; 95% CI, 0.53 to 0.80; p < 0.001) and OS (HR, 0.55; 95% CI, 0.44 to 0.69; p < 0.001). There were no differences between chemotherapy and endocrine therapy maintenance in PFS and OS (all p > 0.05). Regardless of the continuum or switch maintenance therapy, showed prolonged survival in MBC patients who were response to first-line treatment.
Conclusion
This study provided evidences for survival benefits of chemotherapy and endocrine therapy maintenance in MBC patients, and there was no difference efficacy between chemotherapy and endocrine therapy maintenance for hormone receptor–positive patients. -
Citations
Citations to this article as recorded by- 6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7)
Fatima Cardoso, Shani Paluch-Shimon, Eva Schumacher-Wulf, Leonor Matos, Karen Gelmon, Matti S. Aapro, Jyoti Bajpai, Carlos H. Barrios, Jonas Bergh, Elizabeth Bergsten-Nordström, Laura Biganzoli, Maria João Cardoso, Lisa A. Carey, Mariana Chavez-MacGregor,
The Breast.2024; 76: 103756. CrossRef - Maintenance endocrine therapy plus bevacizumab for advanced or metastatic breast cancer
Stanislas Quesada, William Jacot
The Lancet Oncology.2022; 23(5): 557. CrossRef
- 6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7)
- 6,035 View
- 162 Download
- 2 Web of Science
- 2 Crossref
- Long Non-coding RNA CCAT1 Sponges miR-454 to Promote Chemoresistance of Ovarian Cancer Cells to Cisplatin by Regulation of Surviving
- De-Ying Wang, Na Li, Yu-Lan Cui
- Cancer Res Treat. 2020;52(3):798-814. Published online March 3, 2020
- DOI: https://doi.org/10.4143/crt.2019.498
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
Colon cancer-associated transcript 1 (CCAT1) was identified as an oncogenic long non-coding RNA (lncRNA) in a variety of cancers. However, there was a lack of understanding of the mechanism by which CCAT1 conferred cisplatin (also known as DDP) resistance in ovarian cancer cells.
Materials and Methods
Cell viability of A2780, SKOV3, A2780/DDP, and SKOV3/DDP cells upon cisplatin treatment was monitored by MTT assay. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) detected the expression levels of CCAT1 and miR-454. The effect of sh-CCAT1 on cisplatin response was investigated in xenografts study. Bioinformatic analysis, luciferase reporter assay and qRT-PCR were conducted to validate the direct interaction among CCAT1, miR-454, and survivin. Apoptosis was determined by flow cytometry after dual staining of Annexin-V-FITC/propidium iodide, and the expression of apoptosis-related proteins Bcl-2, Bax and survivin were detected by qRT-PCR and Western blotting. Xenograft study was conducted to monitor in vivo tumor formation.
Results
CCAT1 was highly expressed in cisplatin-resistant ovarian cancer cell line A2780/DDP and SKOV3/DDP. Knockdown of CCAT1 restored sensitivity to cisplatin in vitro and in vivo. Our data revealed that silencing of CCAT1 promoted cisplatin-induced apoptosis via modulating the expression of pro- or anti-apoptotic proteins Bax, Bcl-2, and survivin. CCAT1 directly interacted with miR-454, and miR-454 overexpression potentiated cisplatin-induced apoptosis. Survivin was identified as a functional target of miR-454, restoration of survivin attenuated the effect of miR-454 on cisplatin response. In addition, miR-454 inhibitor or overexpression of survivin was found to abolish sh-CCAT1–induced apoptosis upon cisplatin treatment.
Conclusion
CCAT1/miR-454/survivin axis conferred cisplatin resistance in ovarian cancer cells. -
Citations
Citations to this article as recorded by- Exploring miRNA profile associated with cisplatin resistance in ovarian cancer cells
Yaman Alghamian, Chadi Soukkarieh, Abdulmunim Aljapawe, Hossam Murad
Biochemistry and Biophysics Reports.2025; 41: 101906. CrossRef - Long Non-Coding RNAs in Ovarian Cancer: Mechanistic Insights and Clinical Applications
Sneha Basu, Revathy Nadhan, Danny N. Dhanasekaran
Cancers.2025; 17(3): 472. CrossRef - Downregulation of LncRNA CCAT1 Enhances Chemosensitivity in Cisplatin‐Resistant Gastric Cancer Cells
Qiong Wu, Chenglou Zhu, Tiantian Zhao, Tianxiang Liu, Mingxu Da
Drug Development Research.2025;[Epub] CrossRef - Latest Update on lncRNA in Epithelial Ovarian Cancer—A Scoping Review
Katarzyna Kwas, Maria Szubert, Jacek Radosław Wilczyński
Cells.2025; 14(7): 555. CrossRef - USP43 impairs cisplatin sensitivity in epithelial ovarian cancer through HDAC2-dependent regulation of Wnt/β-catenin signaling pathway
Lipeng Pei, Feng Zhao, Yi Zhang
Apoptosis.2024; 29(1-2): 210. CrossRef - BIRC5 facilitates cisplatin‐chemoresistance in a m6A‐dependent manner in ovarian cancer
Yadan Fan, Yinglian Pan, Liping Jia, Shuzhen Gu, Binxin Liu, Ziman Mei, Chunyan Lv, Haohao Huang, Genhai Zhu, Qingchun Deng
Cancer Medicine.2024;[Epub] CrossRef - CCAT1 lncRNA is chromatin-retained and post-transcriptionally spliced
Chaya Bohrer, Eli Varon, Eldar Peretz, Gita Reinitz, Noa Kinor, David Halle, Aviram Nissan, Yaron Shav-Tal
Histochemistry and Cell Biology.2024; 162(1-2): 91. CrossRef - Novel players in the development of chemoresistance in ovarian cancer: ovarian cancer stem cells, non-coding RNA and nuclear receptors
Shahil Alam, Pankaj Kumar Giri
Cancer Drug Resistance.2024;[Epub] CrossRef - The roles of long non-coding RNAs in ovarian cancer: from functions to therapeutic implications
Zhong Hu, Lijin Yuan, Xiu Yang, Cunjian Yi, Jinzhi Lu
Frontiers in Oncology.2024;[Epub] CrossRef - Proto-oncogene c-Myb potentiates cisplatin resistance of ovarian cancer cells by downregulating lncRNA NKILA and modulating cancer stemness and LIN28A-let7 axis
Xue-Yan Zhang, Bo-Chi Zhu, Miao He, Shan-Shan Dong
Journal of Ovarian Research.2024;[Epub] CrossRef - Drug resistance biomarkers in ovarian cancer: a bibliometric study from 2017 to 2022
Sindy Cabarca, Carmen Ili, Carlos Vanegas, Laura Gil, Melba Vertel-Morrinson, Priscilla Brebi
Frontiers in Oncology.2024;[Epub] CrossRef - Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update
Emine Bayraktar, Recep Bayraktar, Hulya Oztatlici, Gabriel Lopez-Berestein, Paola Amero, Cristian Rodriguez-Aguayo
Non-Coding RNA.2023; 9(2): 27. CrossRef - Silencing of NLRP3 Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin
Weijia Li, Xibo Zhao, Rujian Zhang, Jiabin Xie, Guangmei Zhang, Jinghua Pan
Mediators of Inflammation.2023; 2023: 1. CrossRef - Long Noncoding RNAs in Ovarian Cancer—Functions and Clinical Applications
Lili Zhong, Xin Li, Yicun Wang, Bin Liu, Xiangfu Ding, Yinlong Zhao
Frontiers in Bioscience-Landmark.2023;[Epub] CrossRef - Sporoderm-Broken Spores of Ganoderma lucidum Sensitizes Ovarian Cancer to Cisplatin by ROS/ERK Signaling and Attenuates Chemotherapy-Related Toxicity
Kaili Cen, Ming Chen, Mengye He, Zhenhao Li, Yinjing Song, Pu Liu, Qi Jiang, Suzhen Xu, Yunlu Jia, Peng Shen
Frontiers in Pharmacology.2022;[Epub] CrossRef - Gomisin J attenuates cerebral ischemia/reperfusion injury by inducing anti-apoptotic, anti-inflammatory, and antioxidant effects in rats
Xiaoli Min, Linping Zhao, Ying Shi, Jian Wang, Hongling Lv, Xiaoxiao Song, Qunyuan Zhao, Qing Zhao, Rui Jing, Jiayi Hu
Bioengineered.2022; 13(3): 6908. CrossRef - MicroRNA as a Potential Therapeutic Molecule in Cancer
Joanna Szczepanek, Monika Skorupa, Andrzej Tretyn
Cells.2022; 11(6): 1008. CrossRef - LncRNA CCAT1 enhances chemoresistance in hepatocellular carcinoma by targeting QKI-5
Chongsheng Xia, Yurui Sun, Yang Li, Junli Ma, Jing Shi
Scientific Reports.2022;[Epub] CrossRef - Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications
Xuehao Zhou, Xiang Ao, Zhaojun Jia, Yiwen Li, Shouxiang Kuang, Chengcheng Du, Jinyu Zhang, Jianxun Wang, Ying Liu
Frontiers in Oncology.2022;[Epub] CrossRef -
miR-21 Targets Long Noncoding RNA PCAT29 to Promote Cell Proliferation in Neuroblastoma
Zhong Jiang, Xianjun Zhou, Lulu Han, Fujiang Li, Xiwei Hao, Qian Dong, Xin Chen
Critical Reviews in Eukaryotic Gene Expression.2022; 32(8): 1. CrossRef - Long noncoding RNAs as therapeutic targets to overcome chemoresistance in ovarian cancer
Linjiao Chen, Jie Wang, Qian Liu
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef - LINC00184 Promotes Ovarian Cancer Cells Proliferation and Cisplatin Resistance by Elevating CNTN1 Expression via Sponging miR-1305
Yuwen Han, Jun You, Yun Han, Yinglei Liu, Menghui Huang, Xiaoyan Lu, Jingjing Chen, Yanli Zheng
OncoTargets and Therapy.2021; Volume 14: 2711. CrossRef - LncRNA CCAT1 downregulation increases the radiosensitivity of non‐small cell lung cancer cells
Zhao Wang
The Kaohsiung Journal of Medical Sciences.2021; 37(8): 654. CrossRef - Long noncoding RNA HULC contributes to paclitaxel resistance in ovarian cancer via miR-137/ITGB8 axis
Bo Huang, Min Wei, Li Hong
Open Life Sciences.2021; 16(1): 667. CrossRef - HOTTIP-miR-205-ZEB2 Axis Confers Cisplatin Resistance to Ovarian Cancer Cells
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Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef - circ_C20orf11 enhances DDP resistance by inhibiting miR-527/YWHAZ through the promotion of extracellular vesicle-mediated macrophage M2 polarization in ovarian cancer
Jun Yin, Hai-Yan Huang, Ying Long, Yan Ma, Maerkeya Kamalibaike, Reyanguli Dawuti, Li Li
Cancer Biology & Therapy.2021; 22(7-9): 440. CrossRef - The Emerging Role of Non-coding RNAs in Drug Resistance of Ovarian Cancer
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Frontiers in Genetics.2021;[Epub] CrossRef - MicroRNAs as the critical regulators of Cisplatin resistance in ovarian cancer cells
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Journal of Ovarian Research.2021;[Epub] CrossRef - The Non-Coding RNAs Inducing Drug Resistance in Ovarian Cancer: A New Perspective for Understanding Drug Resistance
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Frontiers in Oncology.2021;[Epub] CrossRef - Analyzing the whole-transcriptome profiles of ncRNAs and predicting the competing endogenous RNA networks in cervical cancer cell lines with cisplatin resistance
Huimin Lv, Shanshan Jin, Binbin Zou, Yuxiang Liang, Jun Xie, Suhui Wu
Cancer Cell International.2021;[Epub] CrossRef - Study of Neuronal Apoptosis ceRNA Network in Hippocampal Sclerosis of Human Temporal Lobe Epilepsy by RNA-Seq
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- Exploring miRNA profile associated with cisplatin resistance in ovarian cancer cells
- 9,143 View
- 238 Download
- 39 Web of Science
- 38 Crossref
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