Comprehensive Analysis Revealed that CDKN2A is a Biomarker for Immune Infiltrates in Multiple Cancers

Chen, Zheng; Guo, Yingjie; Da, Zhao; Zou, Quan; Yu, Feihong; Zhang, Lijun; Xu, Lei

doi:10.3389/fcell.2021.808208

Cited by 36 publications

(20 citation statements)

References 49 publications

(50 reference statements)

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“…A recent convincing study demonstrated that CDKN2A was a cancer-driver gene that could effectively predict the poor prognosis and clinical status of CRC patients[ 6 ]. Concordant with this, several studies found that CDKN2A was a risk gene for overexpression in CRC and highlighted that increased CDKN2A protein expression, rather than loss of protein expression, was associated with poor prognosis in CRC[ 3 , 19 , 25 , 30 ].…”

Section: Discussionmentioning

confidence: 68%

“…In mice, p53 genes in senescent cells might transform these cells into highly aggressive, cancer-initiating cells with long-term accumulation progressing to a cancerous state[ 23 ]. Another recent study on the inflammatory microenvironment in CRC found significant differences in CDKN2A expression between the epithelium and stroma, with a 10-fold decrease in the epithelium and a 17-fold increase in the stroma[ 24 , 25 ]. This study speculated that the activation of CDKN2A expression in the stroma was influenced by cellular senescence and oncogene activation, and senescent fibroblasts prematurely accumulated in the stroma as a result of chronic inflammation and oxidative stress[ 24 ].…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive proteomic signature and identification of CDKN2A as a promising prognostic biomarker and therapeutic target of colorectal cancer

Wang¹,

Zhou²,

Ge³

et al. 2022

WJCC

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BACKGROUND The carcinogenesis of colorectal cancer (CRC) involves many different molecules and multiple pathways, and the specific mechanism has not been elucidated until now. Existing studies on the proteomic signature profiles of CRC are relatively limited. Therefore, we herein aimed to provide a more comprehensive proteomic signature profile and discover new prognostic markers and therapeutic targets by performing proteomic analysis of CRC and paired normal tissues. AIM To investigate the proteomic signature and identify novel protein prognostic biomarkers of CRC. METHODS Cancer tissues and paired normal tissues were collected from 48 patients who underwent surgical removal at the China-Japan Friendship Hospital from January 2020 to June 2021. Data independent acquisition (DIA) quantitative proteomic analysis was performed using high-performance liquid chromatography–mass spectrometry/mass spectrometry (nano-UHPLC–MS/MS) to identify differentially expressed proteins, among which those with a P adj value ( t test, BH correction) < 0.05 and an absolute fold change (|log 2 FC|) > 2 were identified as potential markers. Differentially expressed proteins were selected by bioinformatics analysis and validated by immunohistochemical tissue microarrays, and their association with prognosis was further analyzed with the Gene Expression Profiling Interactive Analysis database to identify prognostic protein biomarkers of CRC. RESULTS Significantly differential protein expression was observed between cancer tissues and normal tissues. Compared with normal tissues, 1115 proteins were upregulated and 705 proteins were downregulated in CRC based on P adj < 0.05 and |log 2 FC| > 2, and bioinformatics analysis revealed that the differentially expressed proteins were involved in multiple biological processes associated with tumorigenesis, including ribosome biogenesis in eukaryotes, focal adhesion, extracellular matrix-receptor interactions and other tumor metabolism processes. Moreover, cyclin-dependent kinase inhibitor 2A (CDKN2A) expression was markedly upregulated in CRC, as validated by immunohistochemistry (0.228 vs 0.364, P = 0.0044), and was significantly enriched in tumor proliferation and signal transduction pathways such as the cell cycle and p53 signaling pathways. High CDKN2A expression was significantly correlated with poor prognosis ( P = 0.021). These results demonstrated that CDKN2A functions as a driver of CRC. CONCLUSION Our study provides a comprehensive proteomic signature of CRC and highlights CDKN2A as a potential powerful prognostic marker and precision therapeutic target.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Comprehensive proteomic signature and identification of CDKN2A as a promising prognostic biomarker and therapeutic target of colorectal cancer

Wang¹,

Zhou²,

Ge³

et al. 2022

WJCC

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“…It is worth noting that CDKN2A is a Protein Coding gene. Diseases related to CDKN2A include Cutaneous Malignant Melanoma 15–18 . Among its associated pathways are DNA Damage Response and Mitotic G1‐G1/S phases 19 .…”

Section: Discussionmentioning

confidence: 99%

“…Hence, cellular senescence might exert a basic effect on the occurrence and development of HNSCC. We [15][16][17][18] Among its associated pathways are DNA Damage Response and Mitotic G1-G1/S phases. 19 IL1A (Interleukin 1 Alpha) is related to cytokine activity and interleukin-1 receptor binding and its associated pathways are IL1α-NF-κB pathway and cytokine signaling in Immune system.…”

Section: Discussionmentioning

confidence: 99%

Identification of several senescence‐associated genes signature in head and neck squamous cell carcinoma

Wang

Zhou

Sun

et al. 2022

Clinical Laboratory Analysis

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Background As one of the core aging processes, cellular senescence is associated with tumorigenesis, growth, and immune modulation in cancers. Nevertheless, the prognosis of senescence‐associated genes (SAGs) signature in head and neck squamous cell carcinoma (HNSCC) remains to be further evaluated. Methods The transcriptome and corresponding clinical datasets of SAGs in patients with HNSCC were downloaded from public databases. A new prognostic SAGs signature was established with least absolute shrinkage and selection operator discussion. Patients with HNSCC were fallen into two risk groups based on each sample's risk mark and the cutoff point. The survival analysis was extended to determine the predictive accuracy of the SAGs signature. Furthermore, the evaluation of SAGs signature was made according to clinicopathological characteristics, survival state, the infiltration of inflammatory cells, and efficacy of immunotherapy. Results 41 SAGs were recognized and adopted to establish the forecast signature. The survival analysis indicated that patients with HNSCC in the high‐senescent score group had significantly reduced overall survival compared with those in the low‐senescent score group. It was certified that the risk score of SAGs signature was a separate predicting agent for HNSCC applying Cox regression analysis. According to functional analysis, some immune‐associated pathways were increased in the low‐senescent score group significantly. High‐senescent score group was correlated with poor clinicopathological characteristics, given less the infiltration of inflammatory cells state and worse immunotherapeutic effect. Conclusion A new SAG signature predicting result and response to immunotherapy of HNSCC was identified. Cellular senescence may be a hidden target for HNSCC.

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“…Although various studies have classified CDKN2A as a tumor suppressor, some studies have identified its complex role in tumors ( Rangel et al, 2022 ). It was reported that the expression of the CDKN2A gene was significantly higher in 15 tumors, and the CDKN2A expression level was significantly correlated with the TMB, microsatellite instability, and infiltrating lymphocyte ( Chen et al, 2021 ). In addition, high CDKN2A expression and low FGFR3 expression were statistically significantly associated with worse PFS ( Breyer et al, 2018 ) and were associated with a higher grade ( Quentin et al, 2004 ; Ploussard et al, 2011 ; Abat et al, 2014 ).…”

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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Comprehensive Analysis Revealed that CDKN2A is a Biomarker for Immune Infiltrates in Multiple Cancers

Cited by 36 publications

References 49 publications

Comprehensive proteomic signature and identification of CDKN2A as a promising prognostic biomarker and therapeutic target of colorectal cancer

Comprehensive proteomic signature and identification of CDKN2A as a promising prognostic biomarker and therapeutic target of colorectal cancer

Identification of several senescence‐associated genes signature in head and neck squamous cell carcinoma

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

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