scholarly journals Integrated bioinformatics analysis identified MTHFD1L as a potential biomarker and correlated with immune infiltrates in hepatocellular carcinoma

2021 ◽  
Vol 41 (2) ◽  
Author(s):  
Junhui Chen ◽  
Jie Yang ◽  
Qingchun Xu ◽  
Zhenyu Wang ◽  
Jun Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Proportional Hazards ◽  
Liver Tumors ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Potential Biomarker ◽  
Methylenetetrahydrofolate Dehydrogenase ◽  
Cancer Genome Atlas ◽  
Malignant Liver ◽  
Liver Hepatocellular Carcinoma

Abstract Liver hepatocellular carcinoma (LIHC) is one of the most frequently occurring primary malignant liver tumors and seriously harms people’s health in the world. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) has been shown to be associated with colon cancer cell proliferation, colony formation and invasion. In the present study, a total of 370 LIHC and 51 normal samples data were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatics and immunohistochemistry (IHC) analysis showed that MTHFD1L is highly expressed in liver tumors. Correlation analysis suggested the differences of vital status between high- and low-expression MTHFD1L groups of LIHC. Univariate and multivariate Cox proportional hazards regression were performed to identify the relationship between clinical characteristics and overall survival (OS). In addition, to explore whether MTHFD1L has an effect on the immune infiltration of LIHC. The correlation between MTHFD1L expression and 24 immune cells were analyzed by ImmuneCellAI database. Furthermore, we combined three databases CIBERSORT, TIMER and ImmuneCellAI to do a comprehensive validation and determined that dendritic cells (DCs) resting, macrophage M0 and macrophage M2 closely related to the expression of MTHFD1L. The results showed that MTHFD1L was a potential prognostic biomarker for LIHC, and could help to elucidate that how the immune microenvironment promotes liver cancer development.

scholarly journals Comprehensive analysis of immune-related prognostic genes in the tumour microenvironment of hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Weike Gao ◽  
Luan Li ◽  
Xinyin Han ◽  
Siyao Liu ◽  
Chengzhen Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Proportional Hazards ◽  
Immune Cell ◽  
Prognostic Index ◽  
Tumour Microenvironment ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Potential Biomarker

Abstract Background The mortality rate of hepatocellular carcinoma (HCC) remains high worldwide despite surgery and chemotherapy. Immunotherapy is a promising treatment for the rapidly expanding HCC spectrum. Therefore, it is necessary to further explore the immune-related characteristics of the tumour microenvironment (TME), which plays a vital role in tumour initiation and progression. Methods In this research, 866 immune-related differentially expressed genes (DEGs) were identified by integrating the DEGs of samples from The Cancer Genome Atlas (TCGA)-HCC dataset and the immune-related genes from databases (InnateDB; ImmPort). Afterwards, 144 candidate prognostic genes were defined through weighted gene co-expression network analysis (WGCNA). Results Seven immune-related prognostic DEGs were identified using the L1-penalized least absolute shrinkage and selection operator (LASSO) Cox proportional hazards (PH) model, and the ImmuneRiskScore model was constructed on this basis. The prognostic index of the ImmuneRiskScore model was then validated in the relevant dataset. Patients were divided into high- and low-risk groups according to the ImmuneRiskScore. Differences in the immune cell infiltration of patients with different ImmuneRiskScore values were clarified, and the correlation of immune cell infiltration with immunotherapy biomarkers was further explored. Conclusion The ImmuneRiskScore of HCC could be a prognostic marker and can reflect the immune characteristics of the TME. Furthermore, it provides a potential biomarker for predicting the response to immunotherapy in HCC patients.

scholarly journals Associations of Serum Tumor Biomarkers with Integrated Genomic and Clinical Characteristics of Hepatocellular Carcinoma

Liver Cancer ◽  
2021 ◽  
pp. 1-13
Author(s):  
Keun Soo Ahn ◽  
Daniel R. O’Brien ◽  
Yong Hoon Kim ◽  
Tae-Seok Kim ◽  
Hiroyuki Yamada ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Lens Culinaris ◽  
Acid Metabolism ◽  
The Cancer Genome Atlas ◽  
Molecular Characteristics ◽  
Genetic Profile ◽  
Vegf Signaling ◽  
The Usa ◽  
Cancer Genome Atlas ◽  
Liver Hepatocellular Carcinoma

<b><i>Introduction:</i></b> Serum α-fetoprotein (AFP), <i>Lens culinaris</i> agglutinin-reactive AFP (AFP-L3), and des-γ-carboxy­pro­thrombin (DCP) are useful biomarkers of hepatocellular carcinoma (HCC). However, associations among molecular characteristics and serum biomarkers are unclear. We analyzed RNA expression and DNA variant data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) to examine their associations with serum biomarker levels and clinical data. <b><i>Methods:</i></b> From 371 TCGA-LIHC patients, we selected 91 seen at 3 institutions in Korea and the USA and measured AFP, AFP-L3, and DCP from preoperatively obtained serum. We conducted an integrative clinical and molecular analysis, focusing on biomarkers, and validated the findings with the remaining 280 patients in the TCGA-LIHC cohort. <b><i>Results:</i></b> Patients were categorized into 4 subgroups: elevated AFP or AFP-L3 alone (↑AFP&amp;L3), elevated DCP alone (↑DCP), elevation of all 3 biomarkers (elevated levels of all 3 biomarkers [↑All]), and reference range values for all biomarkers (RR). <i>CTNNB1</i> variants were frequently observed in ↑DCP patients (53.8%) and RR patients (38.5%), but ↑DCP patients with a <i>CTNNB1</i> variant had worse survival than RR patients. <i>TP53</i> sequence variants were associated with ↑AFP (30.8%) and ↑DCP (30.8%). The Wnt-β-catenin signaling pathway was activated in the ↑AFP&amp;L3, whereas liver-related Wnt signaling was activated in the RR. TGF-β and VEGF signaling were activated in ↑AFP&amp;L3, whereas dysregulated bile acid and fatty acid metabolism were dominant in ↑DCP. We validated these findings by showing similar results between the test cohort and the remainder of the TCGA-LIHC cohort. <b><i>Conclusions:</i></b> Serum AFP, AFP-L3, and DCP levels can help predict variants in the genetic profile of HCC, especially for <i>TP53</i> and <i>CTNNB1</i>. These findings may facilitate development of an evidence-based approach to treatment.

scholarly journals Prognostic Value of Phosphotyrosine Phosphatases in Hepatocellular Carcinoma

2018 ◽  
Vol 46 (6) ◽  
pp. 2335-2346 ◽  
Author(s):  
Guangyan Zhangyuan ◽  
Yin Yin ◽  
Wenjie Zhang ◽  
WeiWei Yu ◽  
Kangpeng Jin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
The Cancer Genome Atlas ◽  
Expression Levels ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Phosphotyrosine Phosphatases

Background/Aims: During the occurrence and progression of hepatocellular carcinoma (HCC), phosphotyrosine phosphatases (PTPs) are usually described as tumor suppressors or proto-oncogenes, and to some degree are correlated with the prognosis of HCC. Methods: A total of 321 patients from the Cancer Genome Atlas (TCGA) database and 180 patients from our validated cohort with hepatocellular carcinoma were recruited in this study. Kaplan-Meier, univariate and multivariate Cox proportional hazards model were used to evaluate the risk factors for survival. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were applied to detect the expression levels of PTP genes. Results: After screening the data of TCGA, we identified five PTPs as HCC overall survival related PTP genes, among which only three (PTPN12, PTPRN, PTPN18) exhibited differential expression levels in our 180 paired HCC and adjacent tissues (P< 0.001). Further analysis revealed that expression of PTPN18 was positively, but PTPRN was negatively associated with prognosis of HCC both in TCGA cohort and our own cohort. As to PTPN12, results turned out to be opposite according to HBV status. In detail, higher expression of PTPN12 was associated with better outcome in HBV group but worse prognosis in Non-HBV group. Conclusion: Our results suggested that PTPN12, PTPRN and PTPN18 were independent prognostic factors in HCC.

scholarly journals Construction of liver hepatocellular carcinoma-specific lncRNA-miRNA-mRNA network based on bioinformatics analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249881
Author(s):  
Ruifang Wang ◽  
Xiaobo Hu ◽  
Xiaorui Liu ◽  
Lu Bai ◽  
Junsheng Gu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Replication ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Driver Mutations ◽  
Pathway Gene ◽  
Liver Hepatocellular Carcinoma

Liver hepatocellular carcinoma (LIHC) is one of the major causes of cancer-related death worldwide with increasing incidences, however there are very few studies about the underlying mechanisms and pathways in the development of LIHC. We obtained LIHC samples from The Cancer Genome Atlas (TCGA) to screen differentially expressed mRNAs, lncRNAs, miRNAs and driver mutations. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene ontology enrichment analyses and protein–protein interaction (PPI) network were performed. Moreover, we constructed a competing endogenous lncRNAs-miRNAs-mRNAs network. Finally, cox proportional hazards regression analysis was used to identify important prognostic differentially expressed genes. Total of 1284 mRNAs, 123 lncRNAs, 47 miRNAs were identified within different tissues of LIHC patients. GO analysis indicated that upregulated and downregulated differentially expressed mRNAs (DEmRNAs) were mainly associated with cell division, DNA replication, mitotic sister chromatid segregation and complement activation respectively. Meanwhile, KEGG terms revealed that upregulated and downregulated DEmRNAs were primarily involved in DNA replication, Metabolic pathways, cell cycle and Metabolic pathways, chemical carcinogenesis, retinol metabolism pathway respectively. Among the DERNAs, 542 lncRNAs-miRNAs-mRNAs pairs were predicted to construct a ceRNA regulatory network including 35 DElncRNAs, 26 DEmiRNAs and 112 DEmRNAs. In the Kaplan‐Meier analysis, total of 43 mRNAs, 14 lncRNAs and 3 miRNAs were screened out to be significantly correlated with overall survival of LIHC. The mutation signatures were analyzed and its correlation with immune infiltrates were evaluated using the TIMER in LIHC. Among the mutation genes, TTN mutation is often associated with poor immune infiltration and a worse prognosis in LIHC. This work conducted a novel lncRNAs-miRNAs-mRNAs network and mutation signatures for finding potential molecular mechanisms underlying the development of LIHC. The biomarkers also can be used for predicting prognosis of LIHC.

scholarly journals Association of Estrogen Receptor Alpha Expression With Survival in Oropharyngeal Cancer Following Chemoradiation Therapy

2019 ◽  
Vol 111 (9) ◽  
pp. 933-942 ◽  
Author(s):  
Maria B Koenigs ◽  
Armida Lefranc-Torres ◽  
Juliana Bonilla-Velez ◽  
Krupal B Patel ◽  
D Neil Hayes ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Mrna Expression ◽  
Proportional Hazards ◽  
Hpv Infection ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Rank Tests ◽  
Potential Biomarker ◽  
Hpv Status ◽  
Log Rank Tests

Abstract Background Oropharyngeal squamous carcinoma (OPSC) continues to increase in incidence secondary to human papillomavirus (HPV) infection. Despite the good overall prognosis for these patients, treatment with chemoradiation is associated with morbidity and treatment failure. Better predictors for disease outcome are needed to guide de-intensification regimens. We hypothesized that estrogen receptor α (ERα), a prognostic biomarker in oncology with therapeutic implications, might have similar utility in OPSC. Methods To investigate associations among ERα and demographics, HPV status, and survival, we analyzed ERα mRNA expression of head and neck squamous carcinomas (HNSC) from The Cancer Genome Atlas (TCGA) and immunohistochemistry (IHC) of pretreatment biopsy specimens from an independent group of 215 OPSC patients subsequently treated with primary chemoradiation (OPSC-CR). Associations among variables were evaluated with Fisher exact tests and logistic regression; associations with survival were evaluated with log-rank tests and Cox proportional hazards regression. Results Among 515 patients in TCGA, ERα mRNA expression was highest in HPV-positive OPSC. High ERα mRNA expression was associated with improved survival among those receiving chemoradiation (hazard ratio adjusted for HPV status = 0.44, 95% confidence interval = 0.21 to 0.92). In OPSC-CR, ERα was positive by IHC in 51.6% of tumors and was associated with improved overall, disease-specific, progression-free, and relapse-free survival (log-rank tests: P < .001, P < .001, P = .002, P = .003, respectively); statistically significant associations of ERα positivity with improved survival were maintained after adjusting for clinical risk factors including HPV status. Conclusion In two independent cohorts, ERα is a potential biomarker for improved survival that also may represent a therapeutic target in OPSC.

scholarly journals From big data to diagnosis and prognosis: gene expression signatures in liver hepatocellular carcinoma

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3089 ◽  
Author(s):  
Hong Yang ◽  
Xin Zhang ◽  
Xiao-yong Cai ◽  
Dong-yue Wen ◽  
Zhi-hua Ye ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Big Data ◽  
Natural Language Processing ◽  
Language Processing ◽  
Poor Prognosis ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Liver Hepatocellular Carcinoma ◽  
Genome Atlas

BackgroundLiver hepatocellular carcinoma accounts for the overwhelming majority of primary liver cancers and its belated diagnosis and poor prognosis call for novel biomarkers to be discovered, which, in the era of big data, innovative bioinformatics and computational techniques can prove to be highly helpful in.MethodsBig data aggregated from The Cancer Genome Atlas and Natural Language Processing were integrated to generate differentially expressed genes. Relevant signaling pathways of differentially expressed genes went through Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes and Panther pathway enrichment analysis and protein-protein interaction network. The pathway ranked high in the enrichment analysis was further investigated, and selected genes with top priority were evaluated and assessed in terms of their diagnostic and prognostic values.ResultsA list of 389 genes was generated by overlapping genes from The Cancer Genome Atlas and Natural Language Processing. Three pathways demonstrated top priorities, and the one with specific associations with cancers, ‘pathways in cancer,’ was analyzed with its four highlighted genes, namely, BIRC5, E2F1, CCNE1, and CDKN2A, which were validated using Oncomine. The detection pool composed of the four genes presented satisfactory diagnostic power with an outstanding integrated AUC of 0.990 (95% CI [0.982–0.998],P < 0.001, sensitivity: 96.0%, specificity: 96.5%). BIRC5 (P = 0.021) and CCNE1 (P = 0.027) were associated with poor prognosis, while CDKN2A (P = 0.066) and E2F1 (P = 0.088) demonstrated no statistically significant differences.DiscussionThe study illustrates liver hepatocellular carcinoma gene signatures, related pathways and networks from the perspective of big data, featuring the cancer-specific pathway with priority, ‘pathways in cancer.’ The detection pool of the four highlighted genes, namely BIRC5, E2F1, CCNE1 and CDKN2A, should be further investigated given its high evidence level of diagnosis, whereas the prognostic powers of BIRC5 and CCNE1 are equally attractive and worthy of attention.

scholarly journals High expression of PARD3 predicts poor prognosis in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Songwei Li ◽  
Jian Huang ◽  
Fan Yang ◽  
Haiping Zeng ◽  
Yuyun Tong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dendritic Cells ◽  
Poor Prognosis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Predictive Capacity ◽  
Immune Infiltration ◽  
Cancer Genome Atlas ◽  
Liver Hepatocellular Carcinoma ◽  
The Relationship

AbstractHepatocellular carcinoma (HCC) is one of the most commonly cancers with poor prognosis and drug response. Identifying accurate therapeutic targets would facilitate precision treatment and prolong survival for HCC. In this study, we analyzed liver hepatocellular carcinoma (LIHC) RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), and identified PARD3 as one of the most significantly differentially expressed genes (DEGs). Then, we investigated the relationship between PARD3 and outcomes of HCC, and assessed predictive capacity. Moreover, we performed functional enrichment and immune infiltration analysis to evaluate functional networks related to PARD3 in HCC and explore its role in tumor immunity. PARD3 expression levels in 371 HCC tissues were dramatically higher than those in 50 paired adjacent liver tissues (p < 0.001). High PARD3 expression was associated with poor clinicopathologic feathers, such as advanced pathologic stage (p = 0.002), vascular invasion (p = 0.012) and TP53 mutation (p = 0.009). Elevated PARD3 expression also correlated with lower overall survival (OS, HR = 2.08, 95% CI = 1.45–2.98, p < 0.001) and disease-specific survival (DSS, HR = 2.00, 95% CI = 1.27–3.16, p = 0.003). 242 up-regulated and 71 down-regulated genes showed significant association with PARD3 expression, which were involved in genomic instability, response to metal ions, and metabolisms. PARD3 is involved in diverse immune infiltration levels in HCC, especially negatively related to dendritic cells (DCs), cytotoxic cells, and plasmacytoid dendritic cells (pDCs). Altogether, PARD3 could be a potential prognostic biomarker and therapeutic target of HCC.

scholarly journals An Innovative Immune Score-Based Prognostic Nomogram for Patients with Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xingling Qi ◽  
Yipeng Fu ◽  
Meng Zhang ◽  
Chong Lu ◽  
Yumeng Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Proportional Hazards ◽  
Predictive Performance ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Internal Validation ◽  
Tumor Tissues ◽  
Tumor Immune Microenvironment ◽  
Cancer Genome Atlas ◽  
Immune Score

Background. In the past few years, the immune system and tumor immune microenvironment are becoming increasingly popular as more work has been accomplished in this field. However, nomograms based on immune-related characteristics for prognosis prediction of cervical cancer have not been fully explored to our knowledge. We constructed a novel immune score-based nomogram to predict patients with high risk and poor prognosis. Materials and Methods. 198 patients with cervical cancer from The Cancer Genome Atlas (TCGA) database were included in our study. Immune scores were generated with Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm, and clinic-pathological characteristics were also included for subsequent analysis. Cox proportional hazards regression models were performed for univariate and multivariate analyses to screen the significant factors, and a prognostic nomogram was built. Bootstrap resampling analysis was used for internal validation. The calibration curve and concordance index (C-index) were used to assess the predictive performance of the nomogram. Results. Patients were split into three subgroups based on immune scores. We found that patients with high immune scores conferred significantly better overall survival (OS) compared with those with medium and low immune scores (hazard ratio (HR), 0.305; 95% confidence interval (CI), 0.108-0.869). A nomogram with a C-index of 0.720 had a favorable performance for predicting survival rate for clinical use by combining immune scores with other clinical features. The calibration curves at 3 and 5 years suggested a good consistency between the predicted OS and the actual OS probability. Conclusions. Our work highlights the potential clinical application significance of immune score-based nomogram in predicting the OS of cervical cancer patients.

scholarly journals A Prognostic Nomogram Based on Immune Scores Predicts Postoperative Survival for Patients with Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Jukun Wang ◽  
Chao Zhang ◽  
Ang Li ◽  
Feng Cao ◽  
Dongbin Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Proportional Hazards ◽  
Disease Free Survival ◽  
Predictive Performance ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Calibration Plot ◽  
Research Attention ◽  
Probability Of Survival ◽  
Immune Score

Background. Increasing research attention has focused on tumor-infiltrating immune cells. However, the threshold of an immune score for use in predicting overall survival (OS) and disease-free survival (DFS) in hepatocellular carcinoma (HCC) is not defined. This study aims at exploring the association between immune scores with prognosis and building a clinical nomogram for predicting the survival of HCC patients. Material and Methods. A total of 299 patients were enrolled in this study. Their clinical pathological characteristics and immune scores downloaded from The Cancer Genome Atlas (TCGA) database were analyzed. Survival differences between different immune score subgroups were compared, and a final nomogram was built using the Cox proportional hazards regression model. The predictive performance of the nomogram was assessed using the concordance index (C-index) and a calibration plot. Results. All the patients were divided into three subgroups based on immune scores. Patients with medium and high immune scores had significantly better OS (HR and 95% CI: 0.417 [0.186-0.937] and 0.299 [0.146-0.616]) and DFS (HR and 95% CI: 0.575 [0.329-1.004] and 0.451 [0.278-0.733], respectively, compared with those with low immune scores. The C indices for OS and DFS were 0.748 (95% CI, 0.687-0.809) and 0.675 (95% CI, 0.630-0.720), respectively. A calibration plot used to determine the probability of survival at 3 or 5 years (OS and DFS) showed a significant agreement between nomogram predictions and actual observations. Conclusions. Medium and high immune scores are significantly associated with prolonged OS and DFS in HCC patients. Nomograms built in this study can help doctors and patients assess prognosis and guide treatment.

Decreased expression of ARID1A invasively downregulates the expression of ribosomal proteins in hepatocellular carcinoma

2021 ◽  
Author(s):  
Jing Zhao ◽  
Weiran Xu ◽  
Yu Zhang ◽  
Xiaomin Lv ◽  
Yiran Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Cells ◽  
Ribosomal Proteins ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Reverse Transcription Pcr ◽  
Adaptive Mechanisms ◽  
Tumor Mutational Burden ◽  
Cancer Genome Atlas ◽  
Liver Hepatocellular Carcinoma

Background: There was increasing evidence showing that ARID1A alterations correlated with higher tumor mutational burden, but there were limited studies focusing on the adaptive mechanisms for tumor cells to survive under excessive genomic alterations. Materials & methods: To further explore the adaptive mechanisms under ARID1A alterations, we performed RNA sequencing in ARID1A knockdown hepatocellular carcinoma cell lines, and demonstrated that decreased expression of ARID1A controlled global ribosomal proteins synthesis. The results were further confirmed by quantitative reverse transcription-PCR and bioinformatic analysis in The Cancer Genome Atlas Liver Hepatocellular Carcinoma database. Conclusion: The present study was the first to demonstrate that ARID1A might be involved in the translation pathway and served as an adaptive mechanism for tumor cells to survive under stress.

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