A Novel 7 RNA-based Signature for Prediction of Prognosis and Therapeutic Responses of Wild-type BRAF Cutaneous Melanoma

Overview

Journal Biol Proced Online

Publisher Biomed Central

Specialty Biomedical Engineering

Date 2022 Jun 24

PMID 35751033

Authors

Ruizheng Sun

Yaozhong Liu

Cheng Lei

Zhenwei Tang

Lixia Lu

Affiliations

Soon will be listed here.

Abstract

Background: The prognosis of wild-type BRAF cutaneous melanoma (WT Bf-CM) patients remains poor due to the lack of therapeutic options. However, few studies have investigated the factors contributing to the prognosis of WT Bf-CM patients.

Methods: In this paper, we proposed and validated a novel 7-RNA based signature to predict the prognosis of WT Bf-CM by analyzing the information from TCGA database.

Results: Dependence of this signature to other clinical factors were verified and a nomogram was also drawn to promote its application in clinical practice. Functional analysis suggested that the predictive function of this signature might attribute to the prediction of the up-regulation of RNA splicing, transcription, and cellular proliferation in the high-risk group, which have been demonstrated to be linked to malignancy of cancer. Moreover, functional analysis and therapy response analysis supported that the prognosis is highly related to PI3K/Akt/mTOR pathway among WT Bf-CM patients.

Conclusion: Collectively, this study will provide a preliminary bioinformatics evidence for the molecular mechanism and potential drug targets that could improving WT Bf-CM prognosis.

References

Verduzco D, Kuenzi B, Kinose F, Sondak V, Eroglu Z, Rix U . Ceritinib Enhances the Efficacy of Trametinib in -Wild-Type Melanoma Cell Lines. Mol Cancer Ther. 2017; 17(1):73-83. PMC: 5752595. DOI: 10.1158/1535-7163.MCT-17-0196. View

Vickers A, Cronin A, Elkin E, Gonen M . Extensions to decision curve analysis, a novel method for evaluating diagnostic tests, prediction models and molecular markers. BMC Med Inform Decis Mak. 2008; 8:53. PMC: 2611975. DOI: 10.1186/1472-6947-8-53. View

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

Jiang Y, Shi X, Zhao Q, Krauthammer M, Gould Rothberg B, Ma S . Integrated analysis of multidimensional omics data on cutaneous melanoma prognosis. Genomics. 2016; 107(6):223-30. PMC: 4893887. DOI: 10.1016/j.ygeno.2016.04.005. View

Yang S, Xu J, Zeng X . A six-long non-coding RNA signature predicts prognosis in melanoma patients. Int J Oncol. 2018; 52(4):1178-1188. PMC: 5843393. DOI: 10.3892/ijo.2018.4268. View

Wang J, Zuo J, Wahafu A, Wang M, Li R, Xie W . Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma. CNS Neurosci Ther. 2019; 26(3):297-308. PMC: 7053231. DOI: 10.1111/cns.13197. View

Schadendorf D, van Akkooi A, Berking C, Griewank K, Gutzmer R, Hauschild A . Melanoma. Lancet. 2018; 392(10151):971-984. DOI: 10.1016/S0140-6736(18)31559-9. View

Guo W, Zhu L, Zhu R, Chen Q, Wang Q, Chen J . A four-DNA methylation biomarker is a superior predictor of survival of patients with cutaneous melanoma. Elife. 2019; 8. PMC: 6553943. DOI: 10.7554/eLife.44310. View

Jessurun C, Vos J, Limpens J, Luiten R . Biomarkers for Response of Melanoma Patients to Immune Checkpoint Inhibitors: A Systematic Review. Front Oncol. 2017; 7:233. PMC: 5625582. DOI: 10.3389/fonc.2017.00233. View

10.

Zhou B, Guo R . Integrative analysis of significant RNA-binding proteins in colorectal cancer metastasis. J Cell Biochem. 2018; 119(12):9730-9741. DOI: 10.1002/jcb.27290. View

11.

Davis W, Lehmann P, Li W . Nuclear PI3K signaling in cell growth and tumorigenesis. Front Cell Dev Biol. 2015; 3:24. PMC: 4394695. DOI: 10.3389/fcell.2015.00024. View

12.

Goodman A, Kato S, Bazhenova L, Patel S, Frampton G, Miller V . Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers. Mol Cancer Ther. 2017; 16(11):2598-2608. PMC: 5670009. DOI: 10.1158/1535-7163.MCT-17-0386. View

13.

Hill R, Madureira P, Ferreira B, Baptista I, Machado S, Colaco L . TRIB2 confers resistance to anti-cancer therapy by activating the serine/threonine protein kinase AKT. Nat Commun. 2017; 8:14687. PMC: 5347136. DOI: 10.1038/ncomms14687. View

14.

Hu N, Zhang Y . TLR4 knockout attenuated high fat diet-induced cardiac dysfunction via NF-κB/JNK-dependent activation of autophagy. Biochim Biophys Acta Mol Basis Dis. 2017; 1863(8):2001-2011. DOI: 10.1016/j.bbadis.2017.01.010. View

15.

Li X, Shi Y, Yin Z, Xue X, Zhou B . An eight-miRNA signature as a potential biomarker for predicting survival in lung adenocarcinoma. J Transl Med. 2014; 12:159. PMC: 4062505. DOI: 10.1186/1479-5876-12-159. View

16.

Garbe C, Amaral T, Peris K, Hauschild A, Arenberger P, Bastholt L . European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics - Update 2019. Eur J Cancer. 2020; 126:141-158. DOI: 10.1016/j.ejca.2019.11.014. View

17.

Kumpers C, Jokic M, Haase O, Offermann A, Vogel W, Gratz V . Immune Cell Infiltration of the Primary Tumor, Not PD-L1 Status, Is Associated With Improved Response to Checkpoint Inhibition in Metastatic Melanoma. Front Med (Lausanne). 2019; 6:27. PMC: 6425878. DOI: 10.3389/fmed.2019.00027. View

18.

Wang Q, Wang X, Liang Q, Wang S, Liao X, Li D . Prognostic Value of Dynactin mRNA Expression in Cutaneous Melanoma. Med Sci Monit. 2018; 24:3752-3763. PMC: 6016438. DOI: 10.12659/MSM.910566. View

19.

Shi G, Li H, Gao F, Tan Q . lncRNA H19 predicts poor prognosis in patients with melanoma and regulates cell growth, invasion, migration and epithelial-mesenchymal transition in melanoma cells. Onco Targets Ther. 2018; 11:3583-3595. PMC: 6016262. DOI: 10.2147/OTT.S160143. View

20.

Kohn C, Zeichner S, Chen Q, Montero A, Goldstein D, Flowers C . Cost-Effectiveness of Immune Checkpoint Inhibition in BRAF Wild-Type Advanced Melanoma. J Clin Oncol. 2017; 35(11):1194-1202. PMC: 5791832. DOI: 10.1200/JCO.2016.69.6336. View