Ling Xue1,2, Pingfan Wu1,2, Xiaowen Zhao1,2, Xiaojie Jin3, Jingjing Wang1, Yuxiang Shi1, Xiaojing Yang1, Yali She3, Yaling Li1,3, Changtian Li1. 1. College of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, People's Republic of China. 2. Department of Pathology, The 940th Hospital of the Joint Logistic Support of the People's Liberation Army, Lanzhou, 730050, People's Republic of China. 3. Provincial-Level Key Laboratory of Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, People's Republic of China.
Abstract
BACKGROUND: Cutaneous melanoma is a highly malignant skin tumor, and most patients have a poor prognosis. In recent years, immunotherapy has assumed an important role in the treatment of advanced cutaneous melanoma, but only a small percentage of patients benefit from immunotherapy. A growing number of studies have demonstrated that the prognosis of patients with cutaneous melanoma is closely related to long non-coding RNA and the tumor immune microenvironment. METHODS: We downloaded RNA expression data and immune-related gene lists of cutaneous melanoma patients separately from The Cancer Genome Atlas database and ImmPort website and identified immune-related lncRNAs by co-expression analysis. The prognostic model was constructed by applying least absolute shrinkage and selection operator regression, and all patients were classified into high- and low-risk groups according to the risk score of the model. We evaluated the differences between the two groups in terms of survival outcomes, immune infiltration, pathway enrichment, chemotherapeutic drug sensitivity and immune checkpoint gene expression to verify the impact of lncRNA signature on clinical prognosis and immunotherapy efficacy. RESULTS: By correlation analysis and LASSO regression analysis, we constructed an immune-related lncRNA prognostic model based on five lncRNA: HLA-DQB1-AS1, MIR205HG, RP11-643G5.6, USP30-AS1 and RP11-415F23.4. Based on this model, we plotted Kaplan-Meier survival curves and time-dependent ROC curves and analyzed its ability as an independent prognostic factor for cutaneous melanoma in combination with clinicopathological features. The results showed that these lncRNA signature was an independent prognostic factor of cutaneous melanoma with favorable prognostic ability. Our results also show a higher degree of immune infiltration, higher expression of immune checkpoint-associated genes, and better outcome of immunotherapy in the low-risk group of the lncRNA signature. CONCLUSION: The 5 immune-related lncRNA signatures constructed in our study can predict the prognosis of cutaneous melanoma and contribute to the selection of immunotherapy.
BACKGROUND: Cutaneous melanoma is a highly malignant skin tumor, and most patients have a poor prognosis. In recent years, immunotherapy has assumed an important role in the treatment of advanced cutaneous melanoma, but only a small percentage of patients benefit from immunotherapy. A growing number of studies have demonstrated that the prognosis of patients with cutaneous melanoma is closely related to long non-coding RNA and the tumor immune microenvironment. METHODS: We downloaded RNA expression data and immune-related gene lists of cutaneous melanoma patients separately from The Cancer Genome Atlas database and ImmPort website and identified immune-related lncRNAs by co-expression analysis. The prognostic model was constructed by applying least absolute shrinkage and selection operator regression, and all patients were classified into high- and low-risk groups according to the risk score of the model. We evaluated the differences between the two groups in terms of survival outcomes, immune infiltration, pathway enrichment, chemotherapeutic drug sensitivity and immune checkpoint gene expression to verify the impact of lncRNA signature on clinical prognosis and immunotherapy efficacy. RESULTS: By correlation analysis and LASSO regression analysis, we constructed an immune-related lncRNA prognostic model based on five lncRNA: HLA-DQB1-AS1, MIR205HG, RP11-643G5.6, USP30-AS1 and RP11-415F23.4. Based on this model, we plotted Kaplan-Meier survival curves and time-dependent ROC curves and analyzed its ability as an independent prognostic factor for cutaneous melanoma in combination with clinicopathological features. The results showed that these lncRNA signature was an independent prognostic factor of cutaneous melanoma with favorable prognostic ability. Our results also show a higher degree of immune infiltration, higher expression of immune checkpoint-associated genes, and better outcome of immunotherapy in the low-risk group of the lncRNA signature. CONCLUSION: The 5 immune-related lncRNA signatures constructed in our study can predict the prognosis of cutaneous melanoma and contribute to the selection of immunotherapy.
Authors: Franck Pagès; Bernhard Mlecnik; Florence Marliot; Gabriela Bindea; Fang-Shu Ou; Carlo Bifulco; Alessandro Lugli; Inti Zlobec; Tilman T Rau; Martin D Berger; Iris D Nagtegaal; Elisa Vink-Börger; Arndt Hartmann; Carol Geppert; Julie Kolwelter; Susanne Merkel; Robert Grützmann; Marc Van den Eynde; Anne Jouret-Mourin; Alex Kartheuser; Daniel Léonard; Christophe Remue; Julia Y Wang; Prashant Bavi; Michael H A Roehrl; Pamela S Ohashi; Linh T Nguyen; SeongJun Han; Heather L MacGregor; Sara Hafezi-Bakhtiari; Bradly G Wouters; Giuseppe V Masucci; Emilia K Andersson; Eva Zavadova; Michal Vocka; Jan Spacek; Lubos Petruzelka; Bohuslav Konopasek; Pavel Dundr; Helena Skalova; Kristyna Nemejcova; Gerardo Botti; Fabiana Tatangelo; Paolo Delrio; Gennaro Ciliberto; Michele Maio; Luigi Laghi; Fabio Grizzi; Tessa Fredriksen; Bénédicte Buttard; Mihaela Angelova; Angela Vasaturo; Pauline Maby; Sarah E Church; Helen K Angell; Lucie Lafontaine; Daniela Bruni; Carine El Sissy; Nacilla Haicheur; Amos Kirilovsky; Anne Berger; Christine Lagorce; Jeffrey P Meyers; Christopher Paustian; Zipei Feng; Carmen Ballesteros-Merino; Jeroen Dijkstra; Carlijn van de Water; Shannon van Lent-van Vliet; Nikki Knijn; Ana-Maria Mușină; Dragos-Viorel Scripcariu; Boryana Popivanova; Mingli Xu; Tomonobu Fujita; Shoichi Hazama; Nobuaki Suzuki; Hiroaki Nagano; Kiyotaka Okuno; Toshihiko Torigoe; Noriyuki Sato; Tomohisa Furuhata; Ichiro Takemasa; Kyogo Itoh; Prabhu S Patel; Hemangini H Vora; Birva Shah; Jayendrakumar B Patel; Kruti N Rajvik; Shashank J Pandya; Shilin N Shukla; Yili Wang; Guanjun Zhang; Yutaka Kawakami; Francesco M Marincola; Paolo A Ascierto; Daniel J Sargent; Bernard A Fox; Jérôme Galon Journal: Lancet Date: 2018-05-10 Impact factor: 79.321