Journal Browser
Search
View All
Research Article

N6-methyladenosine-related long noncoding RNA is a potential biomarker for predicting pancreatic cancer prognosis

Yiyang Chen
1
Wanbang Zhou
2
Yiju Gong
2
Xi Ou
1*

1 Anhui Medical University, Clinical College of Peking University Shenzhen Hospital, Fifth Clinical Medical College of Anhui Medical University

2 Peking University Shenzhen Hospital Clinical School, Futian District, Shenzhen, Guangdong Province



Tumor Discovery 2022, 1(2),165; https://doi.org/10.36922/td.v1i2.165
Submitted04 Aug 2022
Revised01 Jan 0001
Accepted23 Sept 2022
Published11 Oct 2022
+
Cite This Article
Yiyang Chen ,Wanbang Zhou ,Yiju Gong ,Xi Ou . (2022). <p>N6-methyladenosine-related long noncoding RNA is a potential biomarker for predicting pancreatic cancer prognosis</p>. Tumor Discovery , 1(2), tdv1i2165. https://doi.org/10.36922/td.v1i2.165
Abstract

Pancreatic cancer is a common malignant tumor of the digestive system, with insidious onset, difficult early diagnosis, easy metastasis, and poor prognosis. N6-methyladenosine (m6A) and long non-coding RNA (lncRNA) play important roles in the prognostic value and immunotherapy response of pancreatic adenocarcinoma (PAAD). Therefore, it is crucial to recognize m6A-related-lncRNAs in PAAD patients. In this study, m6A-related lncRNAs were obtained by coexpression analysis. Univariate, the Least Absolute Shrinkage, and Selection Operator (LASSO) and multivariate Cox regression analyses were performed to construct m6A-related lncRNA prognostic models. Kaplan–Meier analysis, principal component analysis, feature-rich annotation, and nomogram were used to analyze the accuracy of risk models. Potential drugs targeting this model are also discussed. A prognostic model based on m6A-related lncRNAs was constructed, potential drugs targeting this m6A-related lncRNAs feature were discovered, and the relationship with immunotherapy response was studied. Finally, a nomogram was established to predict survival in PAAD patients. This m6A-based lncRNAs risk prognostic model may be promising for clinical prediction of prognosis and immunotherapy response in PAAD patients.

REFERENCES

Yan Q, Ni C, Lin Y, et al., 2021, ELK1 enhances pancreatic cancer progression via LGMN and correlates with poor prognosis. Front Mol Biosci, 8: 764900. https://doi.org/10.3389/fmolb.2021.764900

Liu Y, Cheng L, Song X, et al., 2022, A TP53-associated immune prognostic signature for the prediction of the overall survival and therapeutic responses in pancreatic cancer. Math Biosci Eng, 19(1): 191–208. https://doi.org/10.3934/mbe.2022010

Pratt HG, Steinberger KJ, Mihalik NE, et al., 2021, Macrophage and neutrophil interactions in the pancreatic tumor microenvironment drive the pathogenesis of pancreatic cancer. Cancers (Basel), 14(1): 194. https://doi.org/10.3390/cancers14010194

Luu TT, 2021, Review of immunohistochemistry biomarkers in pancreatic cancer diagnosis. Front Oncol, 11: 799025. https://doi.org/10.3389/fonc.2021.799025

Yang Y, Hsu PJ, Chen YS, et al., 2018, Dynamic transcriptomic m6A decoration: Writers, erasers, readers and functions in RNA metabolism. Cell Res, 28(6): 616–624. https://doi.org/10.1038/s41422-018-0040-8

Choe J, Lin S, Zhang W, et al., 2018, mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis. Nature, 561(7724): 556–560. https://doi.org/10.1038/s41586-018-0538-8

Roundtree IA, Luo GZ, Zhang Z, et al., 2017, YTHDC1 mediates nuclear export of N(6)-methyladenosine methylated mRNAs. Elife, 6: e31311.

Shi H, Wang X, Lu Z, et al., 2017, YTHDF3 facilitates translation and decay of N(6)-methyladenosine-modified RNA. Cell Res, 27(3): 315–328. https://doi.org/10.1038/cr.2017.15

Zhou M, Zhao H, Xu W, et al., 2017, Discovery and validation of immune-associated long non-coding RNA biomarkers associated with clinically molecular subtype and prognosis in diffuse large B cell lymphoma. Mol Cancer, 16(1): 16. https://doi.org/10.1186/s12943-017-0580-4

Zhou M, Xu W, Yue X, et al., 2016, Relapse-related long non-coding RNA signature to improve prognosis prediction of lung adenocarcinoma. Oncotarget, 7(20): 29720–29738. https://doi.org/10.18632/oncotarget.8825

Zhou KI, Parisien M, Dai Q, et al., 2016, N(6)- methyladenosine modification in a long noncoding RNA hairpin predisposes its conformation to protein binding. J Mol Biol, 428(5): 822–833. https://doi.org/10.1016/j.jmb.2015.08.021

Cai H, An Y, Chen X, et al., 2016, Epigenetic inhibition of miR-663b by long non-coding RNA HOTAIR promotes pancreatic cancer cell proliferation via up-regulation of insulin-like growth factor 2. Oncotarget, 7(52): 86857– 86870. https://doi.org/10.18632/oncotarget.13490

Xia T, Wu X, Cao M, et al., 2019, The RNA m6A methyltransferase METTL3 promotes pancreatic cancer cell proliferation and invasion. Pathol Res Pract, 215(11): 152666. https://doi.org/10.1016/j.prp.2019.152666

Tang B, Yang Y, Kang M, et al., 2020, m(6)A demethylase ALKBH5 inhibits pancreatic cancer tumorigenesis by decreasing WIF-1 RNA methylation and mediating Wnt signaling. Mol Cancer, 19(1): 3. https://doi.org/10.1186/s12943-019-1128-6

He Y, Hu H, Wang Y, et al., 2018, ALKBH5 inhibits pancreatic cancer motility by decreasing long non-coding RNA KCNK15-AS1 methylation. Cell Physiol Biochem, 48(2): 838–846. https://doi.org/10.1159/000491915

Tu Z, Wu L, Wang P, et al., 2020, N6-Methylandenosine-related lncRNAs are potential biomarkers for predicting the overall survival of lower-grade glioma patients. Front Cell Dev Biol, 8: 642. https://doi.org/10.3389/fcell.2020.00642

Cho SH, Ha M, Cho YH, et al., 2018, ALKBH5 gene is a novel biomarker that predicts the prognosis of pancreatic cancer: A retrospective multicohort study. Ann Hepatobiliary Pancreat Surg, 22(4): 305–309. https://doi.org/10.14701/ahbps.2018.22.4.305

Li F, Zhang P, Khalaf OI, 2021, The N6-methyladenosine- (m6A-) associated genes act as strong key biomarkers for the prognosis of pancreatic adenocarcinoma. Comput Math Methods Med, 2021: 8715823.

Wei R, Qi G, Zeng Z, et al., 2021, IMUP and GPRC5A: Two newly identified risk score indicators in pancreatic ductal adenocarcinoma. Cancer Cell Int, 21(1): 620. https://doi.org/10.1186/s12935-021-02324-w

Ponting CP, Oliver PL, Reik W, 2009, Evolution and functions of long noncoding RNAs. Cell, 136(4): 629–641. https://doi.org/10.1016/j.cell.2009.02.006

Loewen G, Jayawickramarajah J, Zhuo Y, et al., 2014, Functions of lncRNA HOTAIR in lung cancer. J Hematol Oncol, 7:90. https://doi.org/10.1186/s13045-014-0090-4

Ghafouri-Fard S, Shoorei H, Branicki W, et al., 2020, Non-coding RNA profile in lung cancer. Exp Mol Pathol, 114: 104411. https://doi.org/10.1016/j.yexmp.2020.104411

Dousset L, Poizeau F, Robert C, et al., 2021, Positive association between location of melanoma, ultraviolet signature, tumor mutational burden, and response to anti-PD-1 therapy. JCO Precis Oncol, 5: PO.21.00084.https://doi.org/10.1200/PO.21.00084

Allgauer M, Budczies J, Christopoulos P, et al., 2018, Implementing tumor mutational burden (TMB) analysis in routine diagnostics-a primer for molecular pathologists and clinicians. Transl Lung Cancer Res, 7(6): 703–715. https://doi.org/10.21037/tlcr.2018.08.14

Liu J, Geng R, Yang S, et al., 2021, Development and clinical validation of novel 8-gene prognostic signature associated with the proportion of regulatory T cells by weighted gene co-expression network analysis in uterine corpus endometrial carcinoma. Front Immunol, 12: 788431. https://doi.org/10.3389/fimmu.2021.788431

Mayer P, Gaida MM, 2021, The microarchitecture of pancreatic cancer from the point of view of the pathologist and the radiologist. Pathologe, 42(5): 524–529. https://doi.org/10.1007/s00292-021-00949-2

TOP