Identification and prognostic analysis of biomarkers to predict the progression of pancreatic cancer patients

Li, Wei; Li, Tiandong; Sun, Chenguang; Du, Yangge; Chen, Linna; Du, Chunyan; Shi, Jianxiang; Wang, Weijie

doi:10.1186/s10020-022-00467-8

Cited by 26 publications

(24 citation statements)

References 82 publications

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“…Previous research indicates that immunotherapy may be a promising strategy for PCa [38]. Recently, immune-related genes, such as FN1 and ANXA1, have been identified as prognostic indicators of PCa [39]. Nevertheless, the prognostic significance of these genes needs to be further verified.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Risk Model: A Five-Gene Prognostic Signature for Pancreatic Cancer

Wang

Han

2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Biomarkers for pancreatic cancer (PCa) prognosis provide evidence for improving the survival outcome of this disease. This study aimed to identify a prognostic risk model based on gene expression profiling of microarray bioinformatics analysis. Methods. Prognostic immune genes in the TCGA-PAAD cohort were identified using the univariate Cox regression and Kaplan–Meier survival analysis. Multivariate Cox regression (stepAIC) was used to identify prognostic genes from the top 20 hub genes in the protein-protein interaction (PPI) network. A prognostic risk model was established and its performance in predicting the overall survival in PCa was validated in GSE62452. Gene mutations and infiltration immune cells in PCa tumors were analyzed using online databases. Results. Univariate Cox regression and Kaplan–Meier survival analyses identified 128 prognostic genes. Multivariate Cox regression (stepAIC) identified five prognostic genes (PLCG1, MET, TNFSF10, CXCL9, and TLR3) out of the 20 hub genes in the PPI network. A prognostic risk model was established using the signature of five genes. This model had moderate to high accuracies (AUC > 0.700) in predicting 3-year and 5-year overall survival in TCGA and GSE62452 cohorts. The Kaplan–Meier survival analysis showed that high-risk scores were correlated with poor survival outcomes in PCa ( p < 0.05 ). Also, mutations in the five genes were related to poor survival. The five genes were related to multiple immune cells. Conclusions. The prognostic risk model was significantly correlated with the survival in PCa patients. This model modulated PCa tumor progression and prognosis by regulating immune cell infiltration.

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Section: Discussionmentioning

confidence: 99%

Identification of a Novel Risk Model: A Five-Gene Prognostic Signature for Pancreatic Cancer

Wang

Han

2022

Evidence-Based Complementary and Alternative Medicine

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“…In addition, both ANXA1 expression and S100A9 overexpression by naïve macrophages promote immunosuppression, resist inflammatory processes, and enhance the ability of macrophages to polarize toward the M2 phenotype [ 24 , 109 ]. Therefore, targeting S100A9 and ANXA1 is a potential strategy for clearing TAMs [ 110 , 111 ]. Besides inhibiting signaling molecules that induce M2 macrophage polarization and downregulating M2 macrophage production, studies have also elucidated the mechanisms of directly targeting the recognition signals of M2 macrophages and promoting the apoptotic process of M2 macrophages.…”

Section: Strategies For Targeting Macrophages In the Treatment Of Sol...mentioning

confidence: 99%

Targeting macrophages: a novel treatment strategy in solid tumors

Liu

Song

et al. 2022

J Transl Med

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In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are the most abundant immune cells, which act as a key regulator in tumorigenesis and progression. Increasing evidence have demonstrated that the TME alters the nature of macrophages to maintain dynamic tissue homeostasis, allowing TAMs to acquire the ability to stimulate angiogenesis, promote tumor metastasis and recurrence, and suppress anti-tumor immune responses. Furthermore, tumors with high TAM infiltration have poor prognoses and are resistant to treatment. In the field of solid tumor, the exploration of tumor-promoting mechanisms of TAMs has attracted much attention and targeting TAMs has emerged as a promising immunotherapeutic strategy. Currently, the most common therapeutic options for targeting TAMs are as follows: the deletion of TAMs, the inhibition of TAMs recruitment, the release of phagocytosis by TAMs, and the reprogramming of macrophages to remodel their anti-tumor capacity. Promisingly, the study of chimeric antigen receptor macrophages (CAR-Ms) may provide even greater benefit for patients with solid tumors. In this review, we discuss how TAMs promote the progression of solid tumors as well as summarize emerging immunotherapeutic strategies that targeting macrophages.

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“…The Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment Analysis is a practical resource for the analytical study of gene functions and associated high-level genome functional information. To better understand the carcinogenesis of mRNA, the ClusterProfiler package (version: 3.18.0) of R was employed to analyze the enrichment of the KEGG pathway as our previous described ( 26 ).…”

Section: Methodsmentioning

confidence: 99%

“…Using gene expression markers, TIDE provides insight into two different mechanisms of tumor immune escape, namely dysfunction of tumor-infiltrating cytotoxic T lymphocytes (CTL) and exclusion of CTL by immunosuppressive factors. It has been shown that high TIDE scores are associated with poor immunocheckpoint blockade therapy (ICB) efficacy and short survival following ICB treatment ( 26 ). Therefore, TIDE score is a novel method for predicting ICB responses.…”

Section: Methodsmentioning

confidence: 99%

“…Raw counts of RNA-sequencing data and corresponding clinical information from 36 ICC patients were obtained from TCGA dataset (https://portal.gdc.cancer.gov/), with methods of acquisition and application that comply with the guidelines and policies. Potential ICB response was predicted with a TIDE algorithm, as our and other authors previously described (26,30). Using gene expression markers, TIDE provides insight into two different mechanisms of tumor immune escape, namely dysfunction of tumor-infiltrating cytotoxic T lymphocytes (CTL) and exclusion of CTL by immunosuppressive factors.…”

Section: Icb Responses Analysismentioning

confidence: 99%

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Identification of macrophage correlated biomarkers to predict the prognosis in patients with intrahepatic cholangiocarcinoma

Yan

Long

et al. 2022

Front. Oncol.

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BackgroundIt has been shown that tumor-associated immune cells, particularly macrophages, play a fundamental role in the development and treatment response of intrahepatic cholangiocarcinoma (ICC). However, little is known about macrophages at the single cellular level of ICC patients.MethodsScRNA-seq from Zhang et al. was used in the present study to identify the genes differentially expressed in ICCs. Furthermore, transcriptomic data from TCGA datasets, IHC and flowcytometry from our cohort were used to confirm the findings. Kaplan-Meier and TIDE scores were also used for prognostic analysis and ICB responses.ResultsA significant number of macrophages were found in ICCs as compared to adjacent tissues. We then extracted, processed, and classified the macrophages from the ICCs and adjacent tissues into 12 clusters. Significantly, the macrophages from the ICC exhibited an immunosuppressed state in terms of both signature gene expression and functional enrichment. Furthermore, our results indicate that, of the 10 selective tumor-promoting genes of macrophages, only MMP19 and SIRPα can predict ICB responses in ICCs. Although a higher expression of MMP19 and SIRPα predict a poor prognosis for ICCs without immunotherapy after surgery, patients with high SIRPα expression were more sensitive to immunotherapy, whereas those with high MMP19 expression were not sensitive to immunotherapy. To define the mechanisms, we found that SIRPαhi ICCs exhibited an increased enrichment KEGG pathway of leukocyte transendothelial migration and neutrophil extracellular trap formation. The increased immune cell infiltration will increase sensitivity to immunotherapy.ConclusionCollectively, macrophages are critical to the immune status of ICCs, and MMP19 and SIRPα can predict prognosis and ICB responses for ICCs.

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Identification and prognostic analysis of biomarkers to predict the progression of pancreatic cancer patients

Cited by 26 publications

References 82 publications

Identification of a Novel Risk Model: A Five-Gene Prognostic Signature for Pancreatic Cancer

Identification of a Novel Risk Model: A Five-Gene Prognostic Signature for Pancreatic Cancer

Targeting macrophages: a novel treatment strategy in solid tumors

Identification of macrophage correlated biomarkers to predict the prognosis in patients with intrahepatic cholangiocarcinoma

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