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Tumor Discovery Prognostic biomarkers in pancreatic cancer

N6-methyladenosine (m6A) is a dynamic methylation lncRNAs were identified using the limma package and
modification located at the N6 site of adenosine, which BiocManager package in R studio software. A prognostic
is the most common internal modification in eukaryotic model was constructed based on m6A-related lncRNAs,
mRNA, mediating mRNA splicing, structural switching, which was then used to predict the overall survival of
transport, and translation, degradation and other PAAD patients. Next, potential drugs targeting m6A-
metabolic processes [5-7] . The disordered regulation of related lncRNAs were identified using publicly available
m6A methylation modification may affect the processing, drug sensitivity databases. At the same time, the
degradation, and translation of mRNA, leading to the relationship with immunotherapy response was explored.
activation of oncogenes and the inactivation of tumor Finally, a nomogram was built to predict survival in
suppressor genes, which are closely related to the PAAD patients.
occurrence, development, and drug resistance of malignant
tumors. M6a methylation modification involves the action 2. Materials and methods
of various modifying enzymes, which are the main factors 2.1. Data sources
regulating carcinogenesis and tumor progression . Long
[8]
non-coding RNA (lncRNA) is a general term for a class RNA-seq transcriptome data of PAAD patients were
of non-coding RNAs longer than 200 nucleotides, which obtained from the TCGA (https://cancergenome.nih.
has almost no protein-coding function due to the lack of gov/) database and ID-transformed transcriptome data.
complete open reading frames. Promotion or inhibition Relevant clinical information was downloaded, and
of cancer development can affect the diagnosis and the clinical information of 185 patients was extracted. The
treatment of tumors [9,10] . Changes in RNA can affect a mutation data were downloaded and organized. Pancreatic
variety of biological processes. Therefore, the role of m6A- cancer patients with no survival and incomplete data were
regulated lncRNAs may be crucial for the proliferation excluded to avoid statistical error in this study.
and migration of cancer cells . Besides, studies have 2.2. Selection of m6A genes and m6A-related
[11]
reported that lncRNAs can promote pancreatic cancer cell lncRNAs
proliferation and inhibition of apoptosis .
[12]
Transcriptome expression matrix was obtained by
The m6A methylation modification process is extracting transcriptome data. MRNA and lncRNA were
reversible and involves a variety of enzymes (adenosine distinguished, and the expression levels of m6A-related
methyltransferases, demethylases, and RNA-binding genes were extracted. According to the previous studies,
proteins). Knockout of METTL3 gene expression reduces the expression matrix of 23 m6A genes was retrieved
mRNA m6A methylation modification and attenuates from TCGA which includes writers (METTL3,
[17]
cancer cell proliferation, invasion, and migration . The METTL14, METTL16, WTAP, VIRMA, ZC3H13,
[13]
demethylase ALKBH5 is one of the important predictors RBM15, and RBM15B), readers (YTHDC1, YTHDC2,
of overall survival in pancreatic cancer, and studies have YTHDF1, YTHDF2, YTHDF3, HNRNPC, FMR1, LRPPRC,
found that silencing ALKBH5 can significantly increase the HNRNPA2B1, IGFBP1, IGFBP2, IGFBP3, and RBMX),
proliferation, migration, and invasion of pancreatic cancer and erasers (FTO and ALKBH5) expression data. Using
cells in vitro and in vivo, while its overexpression does the the limma package and BiocManager package in R studio
opposite . The result of another study reported that the software (standard: corFilter > 0.4, p value Filter < 0.001),
[14]
expression level of lncRNAs KCNK15-AS1 and ALKBH5 in the lncRNAs related to m6A were screened, and 288
pancreatic cancer tissues was significantly lower than those lncRNAs with coexpression relationship with m6A were
in normal tissues and after overexpression of ALKBH5 identified. LncRNAs related to m6A were screened out
in different cell lines, the KCNK15-AS1 expression was with limma, tidyverse, ggplot2, and ggExtra packages in R
subsequently increased, while the epithelial-mesenchymal studio software.
transition in pancreatic cancer cells was inhibited [15,16] .
The specific role of m6A regulators in lncRNAs remains 2.3. Construction and validation of prognostic
unclear. Therefore, understanding the mechanism of m6A- models
related-lncRNA in the development of PAAD may provide The entire TCGA dataset was randomized into training and
new ideas for the prognosis and treatment of pancreatic testing groups. A prognostic model was constructed using
cancer patients. the training set, and the established model was validated.
In this study, the expression profiles of 14,056 Subgroups including low-risk and high-risk groups were
lncRNAs and 23 m6A genes were extracted from the also subsequently established based on the median risk
Cancer Genome Atlas (TCGA) dataset. M6A-related score. Combined with the survival information of PAAD

Volume 1 Issue 2 (2022) 2 https://doi.org/10.36922/td.v1i2.165