A Comprehensive Analysis of Pyroptosis-Related lncRNAs Signature Associated With Prognosis and Tumor Immune Microenvironment of Pancreatic Adenocarcinoma

Abstract

Background: Globally, pancreatic adenocarcinoma (PAAD) is a common and highly devastating gastrointestinal malignancy that seriously threatens human health. Pyroptosis refers to an emerging form of programmed cell death that has been discovered in recent years, and studies have demonstrated that long non-coding RNA (lncRNA) may act as a moderator in the pyroptosis process of cancer cells. However, relevant explorations about lncRNAs and pyroptosis are still insufficient in PAAD. Therefore, our research is designed to make a comprehensive analysis of the potential values of pyroptosis-related lncRNAs in PAAD.Methods: By integrating the RNA-sequencing, somatic mutation, and copy number variation (CNV) datasets, as well as the clinicopathological features, we established and validated a risk signature based on pyroptosis-related lncRNAs, and comprehensively analyzed its clinical significance and the potential connection with the tumor immune microenvironment (TIME).Consequences: The genetic variation landscape displayed that the somatic mutations were rare while CNV changes were general and mainly concentrated on copy number amplification of these 52 pyroptosis-related genes. Subsequently, a risk signature consisting of 10 lncRNAs (TRAF3IP2-AS1, LINC00519, LINC01133, LINC02251, AC005332.6, AL590787.1, AC090114.2, TRPC7-AS1, MIR223HG, and MIR3142HG) was constructed and patients were divided into different subgroups according to the median risk score; patients with high-risk scores presented worse outcomes compared to those with low-risk scores in the training, testing, and entire cohorts. Furthermore, patients at low-risk scores possessed a higher infiltration abundance of immune cells compared with high-risk patients, which was consistent with the expression levels of lncRNAs between the high/low-risk groups. Drug sensitivity analysis showed that low-risk scores were related to anti-cancer agents like AICAR and Axitinib, whereas high-risk scores were connected with certain drugs such as AUY922. These results demonstrated that our risk signature could be used for prognosis prediction; additionally, it was also related to the TIME that might act as a potential indicator to instruct immunotherapeutic strategies.Conclusion: This work explored the significance of the risk model constructed by pyroptosis-related lncRNAs in prognosis prediction and its internal link with the immune microenvironment of PAAD. The results are expected to assist in the diagnosis, prognostic assessment, and management of patients with PAAD.

Cuprotosis Programmed-Cell-Death-Related lncRNA Signature Predicts Prognosis and Immune Landscape in PAAD Patients

“…PAAD patients’ prognoses can be predicted by the TMB and risk score ( Figure 12 G). In addition, we found that the TMB predicted the prognosis of PAAD patients in contrast to other common cancers, which was also confirmed by other studies [ 42 ], presumably because pancreatic cancer is a tumor with low immunogenicity [ 43 ], the specific reason for which could be the target of our next exploratory study.…”

“…We used Lasso regression analysis and Cox risk regression analysis to identify five CRLs (AC005332.6, AC090114.2, LINC00857, LINC02041, and AL117382.1) that were shown to be independent prognostic variables for PAAD and correctly classified PAAD patients into two separate prognosis categories. Evidence suggests that AC005332.6, AC090114.2, and LINC02041 may serve as prognostic markers for many cancers, including pancreatic cancer [ 42 , 53 , 54 , 55 , 56 ]. Through a ceRNA-mediated mechanism, LINC00857 promotes the growth and invasion of pancreatic cancer cells [ 51 ].…”

Construction of a cuproptosis-associated long non-coding RNA risk prediction model for pancreatic adenocarcinoma based on the TCGA database

“…[27] AC005332.6 is involved in pyroptosis and ferroptosis in pancreatic adenocarcinoma cells. [28,29] According to the available literature, no study has shown that AC109322.2, AC017048.3, and Z97832.2 are associated with pancreatic cancer development; this study provides the first evidence that these 3 lncRNAs are involved in the cuproptosis pathway in pancreatic adenocarcinoma.…”

A novel approach to PAAD patient care: A 9-cuproptosis-related differential expression lncRNAs model for prognosis prediction

“…Upregulation of LINC01111 expression could be used to cure pancreatic malignant tumors [32].Wanhui Wei established a 7-gene signature that proved to be an excellent model for predicting the prognosis of PAAD patients [33]. Kai Zhao created a 10 pyroptosisrelated lncRNA signature that has a good link with pancreatic patients' survival and PAAD immune in ltration features [34]. However, the function of cuproptosis-related lncRNAs in PAAD is not fully explored.…”