Clinical significance of SQSTM1/P62 and nuclear factor-κB expression in pancreatic carcinoma

Zhang, Zhaoyang; Guo, Shu; Zhao, Rui; Ji, Zhipeng; Zhang, Zhuang

doi:10.4251/wjgo.v12.i7.719

Cited by 5 publications

(2 citation statements)

References 23 publications

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“…Elevated SQSTM1 expression had been reported to support tumorigenesis ( Guo et al, 2011 ). Using 40 cases of tumor tissue chip, elevated SQSTM1 expression was mainly observed in the cytoplasm of pancreatic carcinoma cells and differently expressed among the T stages ( Mohamed et al, 2015 ; Zhang et al, 2020 ). MLKL deficiency prevents the accumulation of SQSTM1 in the liver ( Wu and Nagy, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Establishment of a Necroptosis-Related Prognostic Signature to Reveal Immune Infiltration and Predict Drug Sensitivity in Hepatocellular Carcinoma

et al. 2022

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Background: Hepatocellular carcinoma (HCC) is a common type of primary liver cancer and has a poor prognosis. In recent times, necroptosis has been reported to be involved in the progression of multiple cancers. However, the role of necroptosis in HCC prognosis remains elusive.Methods: The RNA-seq data and clinical information of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Differentially expressed genes (DEGs) and prognosis-related genes were explored, and the nonnegative matrix factorization (NMF) clustering algorithm was applied to divide HCC patients into different subtypes. Based on the prognosis-related DEGs, univariate Cox and LASSO Cox regression analyses were used to construct a necroptosis-related prognostic model. The relationship between the prognostic model and immune cell infiltration, tumor mutational burden (TMB), and drug response were explored.Results: In this study, 13 prognosis-related DEGs were confirmed from 18 DEGs and 24 prognostic-related genes. Based on the prognosis-related DEGs, patients in the TCGA cohort were clustered into three subtypes by the NMF algorithm, and patients in C3 had better survival. A necroptosis-related prognostic model was established according to LASSO analysis, and HCC patients in TCGA and ICGC were divided into high- and low-risk groups. Kaplan–Meier (K–M) survival analysis revealed that patients in the high-risk group had a shorter survival time compared to those in the low-risk group. Using univariate and multivariate Cox analyses, the prognostic model was identified as an independent prognostic factor and had better survival predictive ability in HCC patients compared with other clinical biomarkers. Furthermore, the results revealed that the high-risk patients had higher stromal, immune, and ESTIMATE scores; higher TP53 mutation rate; higher TMB; and lower tumor purities compared to those in the low-risk group. In addition, there were significant differences in predicting the drug response between the high- and low-risk groups. The protein and mRNA levels of these prognostic genes were upregulated in HCC tissues compared to normal liver tissues.Conclusion: We established a necroptosis-related prognostic signature that may provide guidance for individualized drug therapy in HCC patients; however, further experimentation is needed to validate our results.

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Section: Discussionmentioning

confidence: 99%

Establishment of a Necroptosis-Related Prognostic Signature to Reveal Immune Infiltration and Predict Drug Sensitivity in Hepatocellular Carcinoma

et al. 2022

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“…Most likely, BRT reacts with Cys-38 residue of NFκB p65 subunit, as observed with other SLs. This NFκB pathway is frequently activated in pancreatic cancers [74], and the suppression of phospho-p65 contributes to the anti-inflammatory and antiproliferative action. Decreasing phospho-p65 is also a means to augment the efficacy of chemotherapy [75].…”

Section: Interference With the Nfκb Pathwaymentioning

confidence: 99%

Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones

Bailly

2021

Biomedicines

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Sesquiterpene lactones (SLs) are abundant in plants and display a large spectrum of bioactivities. The compound britannin (BRT), found in different Inula species, is a pseudoguaianolide-type SL equipped with a typical and highly reactive α-methylene-γ-lactone moiety. The bioproperties of BRT and related pseudoguaianolide SLs, including helenalin, gaillardin, bigelovin and others, have been reviewed. Marked anticancer activities of BRT have been evidenced in vitro and in vivo with different tumor models. Three main mechanisms are implicated: (i) interference with the NFκB/ROS pathway, a mechanism common to many other SL monomers and dimers; (ii) blockade of the Keap1-Nrf2 pathway, with a covalent binding to a cysteine residue of Keap1 via the reactive α-methylene unit of BRT; (iii) a modulation of the c-Myc/HIF-1α signaling axis leading to a downregulation of the PD-1/PD-L1 immune checkpoint and activation of cytotoxic T lymphocytes. The non-specific reactivity of the α-methylene-γ-lactone moiety with the sulfhydryl groups of proteins is discussed. Options to reduce or abolish this reactivity have been proposed. Emphasis is placed on the capacity of BRT to modulate the tumor microenvironment and the immune-modulatory action of the natural product. The present review recapitulates the anticancer effects of BRT, some central concerns with SLs and discusses the implication of the PD1/PD-L1 checkpoint in its antitumor action.

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Development and validation of a robust epithelial-mesenchymal transition (EMT)-related prognostic signature for hepatocellular carcinoma

Chen

Zhao

2021

Clinics and Research in Hepatology and Gastroenterology

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Clinical significance of SQSTM1/P62 and nuclear factor-κB expression in pancreatic carcinoma

Cited by 5 publications

References 23 publications

Establishment of a Necroptosis-Related Prognostic Signature to Reveal Immune Infiltration and Predict Drug Sensitivity in Hepatocellular Carcinoma

Establishment of a Necroptosis-Related Prognostic Signature to Reveal Immune Infiltration and Predict Drug Sensitivity in Hepatocellular Carcinoma

Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones

Development and validation of a robust epithelial-mesenchymal transition (EMT)-related prognostic signature for hepatocellular carcinoma

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