Correlation between LRP1B Mutations and Tumor Mutation Burden in Gastric Cancer

Hu, Sizhe; Zhao, Xiaokang; Feng, Qian; Jin, Cancan; Hou, Kaishun

doi:10.1155/2021/1522250

Cited by 19 publications

(13 citation statements)

References 35 publications

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“…7E. As expect, most genes were participating in various tumor-associated biological processes in STAD like TP53, TTN and www.nature.com/scientificreports/ LRP1B [54][55][56] . Then, the differentially mutated frequencies were analyzed between the high-risk group and low-risk group, and 928 differentially mutated genes were obtained by Fisher's exact test (p < 0.05).…”

Section: The Different Somatic Mutations Patterns Between High-risk G...supporting

confidence: 56%

Potential mechanisms and prognostic model of eRNAs-regulated genes in stomach adenocarcinoma

Gao

Rong

2022

Sci Rep

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Gastric Carcinoma is the fourth leading cause of cancer deaths worldwide, in which stomach adenocarcinoma (STAD) is the most common histological type. A growing amount of evidence has suggested the importance of enhancer RNAs (eRNAs) in the cancer. However, the potential mechanism of eRNAs in STAD remains unclear. The eRNAs-regulated genes (eRRGs) were identified through four different enhancer resources. The differentially expressed eRRGs were obtained by ‘DESeq2’ R package. The prognosis prediction model was constructed by Cox and Lasso regression analysis. The ‘ChAMP’ R package and ‘maftools’ R package were used to investigate the multi-omics characters. In this study, combining the concept of contact domain, a total of 9014 eRRGs including 4926 PCGs and 4088 lncRNAs were identified and these eRRGs showed higher and more stable expression. Besides, the functions of these genes were mainly associated with tumor-related biological processes. Then, a prognostic prediction model was constructed and the AUC values of the 1-, 3- and 5-year survival prediction reached 0.76, 0.84 and 0.84, respectively, indicating that this model has a high accuracy. Finally, the difference between high-risk group and low-risk group were investigated using multi-omics data including gene expression, DNA methylation and somatic mutations. Our study provides significant clues for the elucidation of eRNAs in STAD and may help improve the overall survival for STAD patients.

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Section: The Different Somatic Mutations Patterns Between High-risk G...supporting

confidence: 56%

Potential mechanisms and prognostic model of eRNAs-regulated genes in stomach adenocarcinoma

Gao

Rong

2022

Sci Rep

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“…Tumor mutation burden (TMB), de ned as the total number of mutations (non-synonymous mutations) detected per million bases in the tumor genome, is a potential biomarker of cancer invasion and metastasis 47 . Our study demonstrated that the high-risk group showed a lower gene mutation density than the low-risk group.…”

Section: Discussionmentioning

confidence: 99%

A novel cuproptosis-related signature for predicting prognosis and immune response in gastric cancer

Liang

Liu

et al. 2023

Preprint

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Cuproptosis is a novel non-apoptotic programmed cell death distinguished from classical cell death. However, the direct prognostic value of cuproptosis-related genes (CRGs), and corresponding detailed mechanisms in gastric cancer (GC) remain unknown. Here, we collected RNA-sequencing data, copy number variation, single nucleotide variation and clinical information of GC from TCGA database. Then, two distinct cuproptosis-related clusters were established based on the expression patterns of 13 CRGs using consensus unsupervised clustering analysis. Based on the differentially expressed genes with prognostic value between the two CRGs clusters, a predictive signature was developed which divided all patients into high- and low-risk two groups. It was found that patients in the low-risk group showed better survival prognosis than those in the high-risk group. Moreover, the accuracy of this model in prognostic prediction was further confirmed in two independent GEO cohorts. Univariate and multivariate Cox regression analyses demonstrated that the CRG score was an independent prognostic predictor for GC patients. In addition, there were also an obvious differences of immune cells infiltration and tumor mutation burden (TMB) between the two groups. Meanwhile, this signature could help to predict chemotherapeutic drug sensitivity and immunotherapy efficacy in GC patients. Collectively, we demonstrated a comprehensive overview of CRG profiles in GC and established a novel risk model for the prediction of therapy effect and prognosis in GC patients.

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“…Patients with LRP1B mutation were identified to be associated with prolonged survival in both melanoma and NCLC cohorts [ 8 ]. Moreover, LRP1B is thought to be a marker of TMB to guide immunotherapy [ 13 , 14 , 26 ]. However, these studies have only conducted multi-omics studies without exploring the specific mechanism.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Low-density lipoprotein receptor-related protein 1B (LRP1B) inhibits the progression of hepatocellular carcinoma cells by activating the endoplasmic reticulum stress signaling pathway

2022

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Hepatocellular carcinoma (HCC) has a high recurrence rate and mortality rate even after surgery. Low-density lipoprotein receptor-related protein 1B (LRP1B) has proven to be involved in tumor development and progression of multiple malignancies. However, the function of LRP1B in HCC progression has not been fully elucidated. Thus, we conducted this study to explore the relationship between LRP1B and HCC. Bioinformatic analyses implied that LRP1B was highly expressed in HCC tissues. High LRP1B expression was shown to be related to poor outcomes and the determination of HCC patients’ tumor stage. LRP1B deletion impeded the proliferation, migration, and invasion of HCC cells. Further investigation demonstrated that silencing LRP1B expression enhanced the sensitivity of HCC cells to doxorubicin. LRP1B deletion inhibited HCC progression by regulating the PERK-ATF4-CHOP signaling pathway. Additionally, we probed the genomic alterations of LRP1B in HCC and the impact on the prognosis of patients. Collectively, our results suggest that LRP1B plays an essential role in the promotion of HCC progression by regulating the PERK-ATF4-CHOP signaling pathway, which is a potential prognostic biomarker and a promising therapeutic target of HCC.

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Correlation between LRP1B Mutations and Tumor Mutation Burden in Gastric Cancer

Cited by 19 publications

References 35 publications

Potential mechanisms and prognostic model of eRNAs-regulated genes in stomach adenocarcinoma

Potential mechanisms and prognostic model of eRNAs-regulated genes in stomach adenocarcinoma

A novel cuproptosis-related signature for predicting prognosis and immune response in gastric cancer

Downregulation of Low-density lipoprotein receptor-related protein 1B (LRP1B) inhibits the progression of hepatocellular carcinoma cells by activating the endoplasmic reticulum stress signaling pathway

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