Cancer Research and Treatment

Original Articles

CXCL-13 Regulates Resistance to 5-Fluorouracil in Colorectal Cancer: Guolin Zhang, Xin Luo, Wei Zhang, Engeng Chen, Jianbin Xu, Fei Wang, Gaoyang Cao, Zhenyu Ju, Dongai Jin, Xuefeng Huang, Wei Zhou, Zhangfa Song; Cancer Res Treat. 2020;52(2):622-633. Published online December 31, 2019; DOI: https://doi.org/10.4143/crt.2019.593

Purpose
5-Fluorouracil (5-Fu) is used as a conventional chemotherapy drug in chemotherapy for patients with advanced colorectal cancer, but many patients still suffer from treatment failure due to 5-Fu resistance. Emerging observations revealed the important role of chemokine (C-X-C motif) ligand 13 (CXCL-13) in tumor microenvironment and its relationship with prognosis in patients with colorectal cancer. This study is designed to reveal the important role of CXCL-13 in causing colorectal cancer resistance to 5-Fu.
Materials and Methods
CXCL-13 levels of patient's serum or cell culture supernatants were measured separately by enzyme-linked immunosorbent assay. In cell assays, cell viability is detected by Cell Counting Kit-8. Therefore, the recombinant human CXCL-13 was used to simulate its high expression in cells while its antibody and siRNA were used to reduce CXCL-13 expression in cells.
Results
In this study, we demonstrated that CXCL-13 is associated with 5-Fu resistance by culture medium exchange experiments and cytokine arrays of colorectal cancer resistant and nonresistant cells. Clinical studies showed that CXCL-13 is highly expressed in the serum of 5-Fu–resistant patients. High levels of serum CXCL-13 also predict a worse clinical outcome. The addition of recombinant CXCL-13 cytokine resulted in 5-Fu resistance, while its antibody overcame 5-Fu resistance, and knockdown of CXCL-13 expression by siRNA also reduced 5-Fu resistance, which can be saved by added recombination CXCL-13.
Conclusion
These results not only identify a CXCL-13 mediated 5-Fu resistance mechanism but also provide a novel target for 5-Fu–resistant colorectal cancer in prevention and treatment strategies.

Citations

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The combination of SHP099 inhibits the malignant biological behavior of L-OHP/5-FU-resistant colorectal cancer cells by regulating energy metabolism reprogramming
Meilian Wang, Kun Yu, Wen Fu, Lihong Yang
Biochemical and Biophysical Research Communications.2024; 728: 150262. CrossRef
Serum CXCL13 as a Novel Biomarker in Oral Squamous Cell Carcinoma
Shin Tojo, Koh‐ichi Nakashiro, Nobuyuki Kuribayashi, Daisuke Uchida
Cancer Medicine.2024;[Epub] CrossRef
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Xunxing Hao, Meng Ding, Chenyu Chi, Xiaodong Xu, Xiaoyu Zhang, Mingzhe Hu
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Jiazheng Li, Chao Yang, Yongbin Zheng
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Prognostic Significance of the CXCLs and Its Impact on the Immune Microenvironment in Ovarian Cancer
Cairu Gu, Xifeng Xiong, Wei Liu, Elisa Belluzzi
Disease Markers.2023; 2023: 1. CrossRef
TIMP-2 as a predictive biomarker in 5-Fu-resistant colorectal cancer
Yaoqing Li, Chuchu Xu, Renjun Zhu, Liyijing Shen, Gengyuan Hu, Kelong Tao, Feng Tao, Zengxin Lu, Guolin Zhang
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Frontiers in Oncology.2023;[Epub] CrossRef
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Hu Chen, Junsei Sameshima, Shiho Yokomizo, Tomoki Sueyoshi, Haruki Nagano, Yuka Miyahara, Taiki Sakamoto, Shinsuke Fujii, Tamotsu Kiyoshima, Thomas Guy, Seiji Nakamura, Masafumi Moriyama, Naoki Kaneko, Shintaro Kawano
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International Journal of Molecular Sciences.2022; 23(7): 3544. CrossRef
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Frontiers in Immunology.2022;[Epub] CrossRef
CXCL13-CXCR5 axis: Regulation in inflammatory diseases and cancer
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Frontiers in Immunology.2022;[Epub] CrossRef
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Shamin Azwar, Heng Fong Seow, Maha Abdullah, Mohd Faisal Jabar, Norhafizah Mohtarrudin
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Retrospective Molecular Epidemiology Study of PD-L1 Expression in Patients with EGFR-Mutant Non-small Cell Lung Cancer: Jong Ho Cho, Wei Zhou, Yoon-La Choi, Jong-Mu Sun, Hyejoo Choi, Tae-Eun Kim, Marisa Dolled-Filhart, Kenneth Emancipator, Mary Anne Rutkowski, Jhingook Kim; Cancer Res Treat. 2018;50(1):95-102. Published online March 17, 2017; DOI: https://doi.org/10.4143/crt.2016.591

Abstract PDF PubReader ePub

Purpose
Data are limited on programmed death ligand 1 (PD-L1) expression in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC).
Materials and Methods
We retrospectively evaluated the relationship between PD-L1 expression and recurrence-free survival (RFS) and overall survival in 319 patients with EGFR-mutant NSCLC who were treated at Samsung Medical Center from 2006 to 2014. Membranous PD-L1 expression on tumor cells was measured using the PD-L1 IHC 22C3 pharmDx antibody and reported as tumor proportion score (TPS). Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis.
Results
All patients had ≥ 1 EGFR mutation—54% in exon 19 and 39% in exon 21. Overall, 51% of patients had PD-L1–positive tumors. The prevalence of PD-L1 positivity was higher among patients with stages II-IV versus stage I disease (64% vs. 44%) and among patients with other EGFR mutations (75%) than with L858R mutation (39%) or exon 19 deletion (52%). PD-L1 positivity was associated with shorter RFS, with an adjusted hazard ratio of 1.52 (95% confidence interval [CI], 0.81 to 2.84; median, 18 months) for the PD-L1 TPS ≥ 50% group, 1.51 (95% CI, 1.02 to 2.21; median, 31 months) for the PD-L1 TPS 1%-49% group, and 1.51 (95% CI, 1.05 to 2.18) for the combined PD-L1–positive groups (TPS ≥ 1%) compared with the PD-L1–negative group (median, 35 months).
Conclusion
PD-L1 expression is associated with disease stage and type of EGFR mutation. PD-L1 positivity might be associated with worse RFS among patients with surgically treated EGFR-mutant NSCLC.

Citations

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Immunological features of EGFR-mutant non-small cell lung cancer and clinical practice: a narrative review
Yi Dong, Liaqat Khan, Yi Yao
Journal of the National Cancer Center.2024; 4(4): 289. CrossRef
Activatable near-infrared fluorescence probe for real-time imaging of PD-L1 expression in tumors
Hyunjin Kim, Maixian Liu, Chan Hyeok Park, Byung Il Lee, Hyonchol Jang, Yongdoo Choi
Journal of Materials Chemistry B.2024; 12(42): 10877. CrossRef
Influence of PD‐L1 expression on the efficacy of EGFR‐TKIs in EGFR‐mutant non‐small cell lung cancer
Si‐Yu Lei, Hai‐Yan Xu, Hong‐Shuai Li, Ya‐Ning Yang, Fei Xu, Jun‐Ling Li, Zhi‐Jie Wang, Pu‐Yuan Xing, Xue‐Zhi Hao, Yan Wang
Thoracic Cancer.2023; 14(24): 2327. CrossRef
Association of PD‐L1 tumor proportion score ≥20% with early resistance to osimertinib in patients with EGFR‐mutated NSCLC
Yusuke Hamakawa, Yoko Agemi, Aya Shiba, Toshiki Ikeda, Yuko Higashi, Masaharu Aga, Kazuhito Miyazaki, Yuri Taniguchi, Yuki Misumi, Yukiko Nakamura, Tsuneo Shimokawa, Yusuke Saigusa, Nobuaki Kobayashi, Hiroaki Okamoto, Takeshi Kaneko
Cancer Medicine.2023; 12(17): 17788. CrossRef
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Yu-Wei Fang, Chieh-Yu Liu
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Edouard Dantoing, Nicolas Piton, Mathieu Salaün, Luc Thiberville, Florian Guisier
International Journal of Molecular Sciences.2021; 22(12): 6288. CrossRef
Programmed Death Ligand 1 Expression and Related Markers in Pleuropulmonary Blastoma
Zahra Alipour, Kris Ann P Schultz, Ling Chen, Anne K Harris, Ivan A Gonzalez, John Pfeifer, D Ashley Hill, Mai He, Louis P Dehner
Pediatric and Developmental Pathology.2021; 24(6): 523. CrossRef
The predictive and prognostic effects of PD-L1 expression on TKI treatment and survival of EGFR-mutant NSCLC
Bo Lan, Yongfang Wang, Jingni Wu, Kai Wang, Pingli Wang
Medicine.2021; 100(34): e27038. CrossRef
The Clinicopathological and Molecular Associations of PD-L1 Expression in Non-small Cell Lung Cancer: Analysis of a Series of 10,005 Cases Tested with the 22C3 Assay
Matthew Evans, Brendan O’Sullivan, Frances Hughes, Tina Mullis, Matthew Smith, Nicola Trim, Philippe Taniere
Pathology & Oncology Research.2020; 26(1): 79. CrossRef
PD-L1 expression and response to pembrolizumab in patients with EGFR-mutant non-small cell lung cancer
Eriko Miyawaki, Haruyasu Murakami, Keita Mori, Nobuaki Mamesaya, Takahisa Kawamura, Haruki Kobayashi, Shota Omori, Kazushige Wakuda, Akira Ono, Hirotsugu Kenmotsu, Tateaki Naito, Toshiaki Takahashi
Japanese Journal of Clinical Oncology.2020; 50(5): 617. CrossRef
Tumor mutation burden and checkpoint immunotherapy markers in primary and metastatic synovial sarcoma
Mai He, Brooj Abro, Madhurima Kaushal, Ling Chen, Tiffany Chen, Mercia Gondim, Weisi Yan, Julie Neidich, Louis P. Dehner, John D. Pfeifer
Human Pathology.2020; 100: 15. CrossRef
Clinicopathological characteristics of primary lung nuclear protein in testis carcinoma: A single‐institute experience of 10 cases
Yoon Ah Cho, Yoon‐La Choi, Inwoo Hwang, Kyungjong Lee, Jong Ho Cho, Joungho Han
Thoracic Cancer.2020; 11(11): 3205. CrossRef
Impact of EGFR mutation on the clinical efficacy of PD-1 inhibitors in patients with pulmonary adenocarcinoma
Jang Ho Cho, Hyun Ae Jung, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Jong-Mu Sun
Journal of Cancer Research and Clinical Oncology.2019; 145(5): 1341. CrossRef
The canonical TGF-β/Smad signalling pathway is involved in PD-L1-induced primary resistance to EGFR-TKIs in EGFR-mutant non-small-cell lung cancer
Yang Zhang, Yuanyuan Zeng, Ting Liu, Wenwen Du, Jianjie Zhu, Zeyi Liu, Jian-an Huang
Respiratory Research.2019;[Epub] CrossRef
Association with PD-L1 Expression and Clinicopathological Features in 1000 Lung Cancers: A Large Single-Institution Study of Surgically Resected Lung Cancers with a High Prevalence of EGFR Mutation
Lee, Kim, Sung, Lee, Han, Kim, Choi
International Journal of Molecular Sciences.2019; 20(19): 4794. CrossRef
Clinical and Molecular Predictors of PD-L1 Expression in Non–Small-Cell Lung Cancer: Systematic Review and Meta-analysis
Fausto Petrelli, Mariangela Maltese, Gianluca Tomasello, Barbara Conti, Karen Borgonovo, Mary Cabiddu, Mara Ghilardi, Michele Ghidini, Rodolfo Passalacqua, Sandro Barni, Matteo Brighenti
Clinical Lung Cancer.2018; 19(4): 315. CrossRef
Status of programmed death-ligand 1 expression in sarcomas
Hyung Kyu Park, Mingi Kim, Minjung Sung, Seung Eun Lee, Yu Jin Kim, Yoon-La Choi
Journal of Translational Medicine.2018;[Epub] CrossRef
Association between PD-L1 expression and driver gene status in non-small-cell lung cancer: a meta-analysis
Bo Lan, Chengxi Ma, Chengyan Zhang, Shoujie Chai, Pingli Wang, Liren Ding, Kai Wang
Oncotarget.2018; 9(7): 7684. CrossRef
Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcinoma
Byung Soo Lee, Dong Il Park, Da Hye Lee, Jeong Eun Lee, Min-kyung Yeo, Yeon Hee Park, Dae Sik Lim, Wonyoung Choi, Da Hye Lee, Geon Yoo, Han-byul Kim, Dahyun Kang, Jae Young Moon, Sung Soo Jung, Ju Ock Kim, Sang Yeon Cho, Hee Sun Park, Chaeuk Chung
Biochemical and Biophysical Research Communications.2017; 491(2): 493. CrossRef

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