paper Serum-derived exosomal miR-125a-3p predicts the response to anti-programmed cell death-1/programmed cell death-ligand 1 monotherapy in patients with non-small cell lung cancer

被引：9

作者：

Hisakane, Kakeru ^{[1
]}

Seike, Masahiro ^{[1
,2
]}

Sugano, Teppei ^{[1
]}

Matsuda, Kuniko ^{[1
]}

Kashiwada, Takeru ^{[1
]}

Nakamichi, Shinji ^{[1
]}

Matsumoto, Masaru ^{[1
]}

Miyanaga, Akihiko ^{[1
]}

Noro, Rintaro ^{[1
]}

Kubota, Kaoru ^{[1
]}

Gemma, Akihiko ^{[1
]}

机构：

[1] Nippon Med Sch, Dept Pulm Med & Oncol, Grad Sch Med, Tokyo, Japan

[2] Nippon Med Sch, Grad Sch Med, Dept Pulm Med & Oncol, 1 1 5, Sendagi, Bunkyou ku, Tokyo 1138603, Japan

来源：

GENE | 2023年 / 857卷

关键词：

Exosome; Immunotherapy; MicroRNA; NSCLC; OPEN-LABEL; NIVOLUMAB; DOCETAXEL; PEMBROLIZUMAB; CHEMOTHERAPY; RESISTANCE; INVASION; PHASE-3;

D O I：

10.1016/j.gene.2023.147177

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background: Versatile biomarkers for immune checkpoint inhibitors (ICI) efficacy in patients with cancer remain to be identified. Liquid biopsy using serum-derived exosomal microRNAs (miRNAs) are widely investigated as diagnostic and therapeutic outcome predictors in patients with cancer. However, exosomal miRNAs linked to the response to ICI in patients with non-small cell lung cancer (NSCLC) remain elusive thus far. Methods: The value of serum-derived exosomal miRNAs in predicting the effect of anti-programmed cell death-1 (PD-1)/anti-programmed cell death-ligand 1 (PD-L1) monotherapy in 41 patients with advanced NSCLC was assessed. We performed functional analysis of candidate miRNAs using NSCLC cell lines. Results: Exosomal miR-125a-3p was associated with response to treatment with ICI. Exosomal miR-125a-3p was more useful in predicting response to ICI versus tumoral PD-L1 in patients with low PD-L1 expression <50 %). Moreover, high expression of miR-125a3p was associated with worse progression-free and overall survival. In H1975 and H441 cells, induction of miR125a-3p regulated PD-L1 expression via suppression of neuregulin 1 (NRG1). Conclusions: Exosomal miR-125a3p is a potential predictor of response to anti-PD-1/PD-L1 therapy in advanced NSCLC patients with low PD-L1 expression.

引用

页数：9

共 42 条

[1] Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].

Borghaei, H. ;

Paz-Ares, L. ;

Horn, L. ;

Spigel, D. R. ;

Steins, M. ;

Ready, N. E. ;

Chow, L. Q. ;

Vokes, E. E. ;

Felip, E. ;

Holgado, E. ;

Barlesi, F. ;

Kohlhaeufl, M. ;

Arrieta, O. ;

Burgio, M. A. ;

Fayette, J. ;

Lena, H. ;

Poddubskaya, E. ;

Gerber, D. E. ;

Gettinger, S. N. ;

Rudin, C. M. ;

Rizvi, N. ;

Crino, L. ;

Blumenschein, G. R. ;

Antonia, S. J. ;

Dorange, C. ;

Harbison, C. T. ;

Finckenstein, F. Graf ;

Brahmer, J. R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639

[2] Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer [J].

Brahmer, Julie ;

Reckamp, Karen L. ;

Baas, Paul ;

Crino, Lucio ;

Eberhardt, Wilfried E. E. ;

Poddubskaya, Elena ;

Antonia, Scott ;

Pluzanski, Adam ;

Vokes, Everett E. ;

Holgado, Esther ;

Waterhouse, David ;

Ready, Neal ;

Gainor, Justin ;

Aren Frontera, Osvaldo ;

Havel, Libor ;

Steins, Martin ;

Garassino, Marina C. ;

Aerts, Joachim G. ;

Domine, Manuel ;

Paz-Ares, Luis ;

Reck, Martin ;

Baudelet, Christine ;

Harbison, Christopher T. ;

Lestini, Brian ;

Spigel, David R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (02) :123-135

[3]

Brierly J.D., 2016, UICC TNM CLASSIFICAT, V8th, P106

[4] A novel neuregulin-jagged1 paracrine loop in breast cancer transendothelial migration [J].

Cabrera, Ramon M. ;

Mao, Serena P. H. ;

Surve, Chinmay R. ;

Condeelis, John S. ;

Segall, Jeffrey E. .

BREAST CANCER RESEARCH, 2018, 20

[5] Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signalling [J].

De Boeck, Astrid ;

Pauwels, Patrick ;

Hensen, Karen ;

Rummens, Jean-Luc ;

Westbroek, Wendy ;

Hendrix, An ;

Maynard, Dawn ;

Denys, Hannelore ;

Lambein, Kathleen ;

Braems, Geert ;

Gespach, Christian ;

Bracke, Marc ;

De Wever, Olivier .

GUT, 2013, 62 (04) :550-560

[6] Mechanisms of the Multitasking Endothelial Protein NRG-1 as a Compensatory Factor During Chronic Heart Failure [J].

De Keulenaer, Gilles W. ;

Feyen, Eline ;

Dugaucquier, Lindsey ;

Shakeri, Hadis ;

Shchendrygina, Anastasia ;

Belenkov, Yury N. ;

Brink, Marijke ;

Vermeulen, Zarha ;

Segers, Vincent F. M. .

CIRCULATION-HEART FAILURE, 2019, 12 (10)

[7]

Fan Z., 2016, ONCOGENESIS, V5, P197

[8] Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer [J].

Gandhi, L. ;

Rodriguez-Abreu, D. ;

Gadgeel, S. ;

Esteban, E. ;

Felip, E. ;

De Angelis, F. ;

Domine, M. ;

Clingan, P. ;

Hochmair, M. J. ;

Powell, S. F. ;

Cheng, S. Y. -S. ;

Bischoff, H. G. ;

Peled, N. ;

Grossi, F. ;

Jennens, R. R. ;

Reck, M. ;

Hui, R. ;

Garon, E. B. ;

Boyer, M. ;

Rubio-Viqueira, B. ;

Novello, S. ;

Kurata, T. ;

Gray, J. E. ;

Vida, J. ;

Wei, Z. ;

Yang, J. ;

Raftopoulos, H. ;

Pietanza, M. C. ;

Garassino, M. C. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (22) :2078-2092

[9] IFN-γ mediated inhibition of lung cancer correlates with PD-L1 expression and is regulated by PI3K-AKT signaling [J].

Gao, Yi ;

Yang, Jianjian ;

Cai, Yixin ;

Fu, Shengling ;

Zhang, Ni ;

Fu, Xiangning ;

Li, Lequn .

INTERNATIONAL JOURNAL OF CANCER, 2018, 143 (04) :931-943

[10] Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer [J].

Garon, Edward B. ;

Rizvi, Naiyer A. ;

Hui, Rina ;

Leighl, Natasha ;

Balmanoukian, Ani S. ;

Eder, Joseph Paul ;

Patnaik, Amita ;

Aggarwal, Charu ;

Gubens, Matthew ;

Horn, Leora ;

Carcereny, Enric ;

Ahn, Myung-Ju ;

Felip, Enriqueta ;

Lee, Jong-Seok ;

Hellmann, Matthew D. ;

Hamid, Omid ;

Goldman, Jonathan W. ;

Soria, Jean-Charles ;

Dolled-Filhart, Marisa ;

Rutledge, Ruth Z. ;

Zhang, Jin ;

Lunceford, Jared K. ;

Rangwala, Reshma ;

Lubiniecki, Gregory M. ;

Roach, Charlotte ;

Emancipator, Kenneth ;

Gandhi, Leena .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (21) :2018-2028

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