Development and Verification of the Hypoxia- and Immune-Associated Prognostic Signature for Pancreatic Ductal Adenocarcinoma

Chen, Dongjie; Huang, Haohai; Zang, Longjun; Gao, Wenzhe; Zhu, Hongwei; Yu, Xiao

doi:10.3389/fimmu.2021.728062

Cited by 38 publications

(26 citation statements)

References 50 publications

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“…This process was performed with 1,000 iterations by sampling 80% of all the data for each iteration to ensure clustering stability. The optimal clustering number was comprehensively determined by the item-consensus plots, the consensus heatmap, and the change in the area under the cumulative distribution function (CDF) curves, which was further confirmed by the proportion of ambiguous clustering (PAC) algorithm ( 28 , 29 ). Two hallmark-guided subtypes with distinct OS outcomes were recognized and visualized with principal component analysis (PCA) plots.…”

Section: Methodsmentioning

confidence: 90%

Hallmark-guided subtypes of hepatocellular carcinoma for the identification of immune-related gene classifiers in the prediction of prognosis, treatment efficacy, and drug candidates

Guo

Tang²,

Zhao³

et al. 2022

Front. Immunol.

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Hepatocellular carcinoma (HCC), accounting for ~90% of all primary liver cancer, is a prevalent malignancy worldwide. The intratumor heterogeneity of its causative etiology, histology, molecular landscape, and immune phenotype makes it difficult to precisely recognize individuals with high mortality risk or tumor-intrinsic treatment resistance, especially immunotherapy. Herein, we comprehensively evaluated the activities of cancer hallmark gene sets and their correlations with the prognosis of HCC patients using gene set variation analysis (GSVA) and identified two HCC subtypes with distinct prognostic outcomes. Based on these subtypes, seven immune-related genes (TMPRSS6, SPP1, S100A9, EPO, BIRC5, PLXNA1, and CDK4) were used to construct a novel prognostic gene signature [hallmark-guided subtypes-based immunologic signature (HGSIS)] via multiple statistical approaches. The HGSIS-integrated nomogram suggested an enhanced predictive performance. Interestingly, oncogenic hallmark pathways were significantly enriched in the high-risk group and positively associated with the risk score. Distinct mutational landscapes and immune profiles were observed between different risk groups. Moreover, immunophenoscore (IPS) and tumor immune dysfunction and exclusion (TIDE) analysis showed different sensitivities of HGSIS risk groups for immune therapy efficacy, and the pRRophetic algorithm indicated distinguishable responses for targeted/chemotherapies in different groups. KIF2C was picked out as the key target concerning HGSIS, and the top 10 small molecules were predicted to bind to the active site of KIF2C via molecular docking, which might be further used for candidate drug discovery of HCC. Taken together, our study offers novel insights for clinically significant subtype recognition, and the proposed signature may be a helpful guide for clinicians to improve the treatment regimens.

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Section: Methodsmentioning

confidence: 90%

Hallmark-guided subtypes of hepatocellular carcinoma for the identification of immune-related gene classifiers in the prediction of prognosis, treatment efficacy, and drug candidates

Guo

Tang²,

Zhao³

et al. 2022

Front. Immunol.

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“…Although its growth can be inhibited to a certain extent through energy metabolism, for some malignant solid tumors, hypoxia can stimulate tumor cell metabolism and changes in malignant behavior, providing a suitable environment for the survival of pancreatic cancer cells ( 33 ). Studies have shown that the hypoxic microenvironment is a key factor in tumor progression, immune escape, and treatment tolerance ( 34 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

Emerging Trends and Research Foci in Tumor Microenvironment of Pancreatic Cancer: A Bibliometric and Visualized Study

Liu²,

Liu

et al. 2022

Front. Oncol.

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BackgroundPancreatic cancer (PC) is a serious disease with high mortality. The tumor microenvironment plays a key role in the occurrence and development of PC. The purpose of this study is to analyze trends by year, country, institution, journal, reference and keyword in publications on the PC microenvironment and to predict future research hotspots.MethodsThe Web of Science Core Collection was used to search for publications. We analyzed the contributions of various countries/regions, institutes, and authors and identified research hotspots and promising future trends using the CiteSpace and VOSviewer programs. We also summarized relevant completed clinical trials.ResultsA total of 2,155 papers on the PC microenvironment published between 2011 and 2021 were included in the study. The number of publications has increased every year. The average number of citations per article was 32.69. The USA had the most publications, followed by China, and a total of 50 influential articles were identified through co-citation analysis. Clustering analysis revealed two clusters of keywords: basic research and clinical application. The co-occurrence cluster analysis showed glutamine metabolism, carcinoma-associated fibroblasts, oxidative phosphorylation as the highly concerned research topics of basic research in recently. The three latest hot topics in clinical application are liposomes, endoscopic ultrasound and photodynamic therapy.ConclusionThe number of publications and research interest have generally increased, and the USA has made prominent contributions to the study of the tumor microenvironment of PC. The current research hotspots mainly focus on energy metabolism in the hypoxic tumor microenvironment, cancer associated fibroblasts in regulating the tumor microenvironment, accurate diagnosis, drug delivery and new treatments.

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“…With a comparable smaller AIC, the Lasso-Cox model outperformed the combination of Cox regression. Actually, Lasso-Cox was adopted in extensive research to determine prognostic molecular features or clinical characteristics [ 20 – 22 ]. For instance, the group Lasso-Cox model was executed to predict patient prognosis and identify risk protein complexes in glioblastoma multiforme, ovarian cancer, and lung adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

Additional Postoperative Radiotherapy Prolonged the Survival of Patients with I-IIA Small Cell Lung Cancer: Analysis of the SEER Database

Zeng

Huang

et al. 2022

Journal of Oncology

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Purpose. Complete resection and adjuvant chemotherapy are recommended as the standard strategy for patients with stage I-IIA small cell lung cancer (SCLC). However, the role of additional postoperative radiotherapy (PORT) in treatment remains controversial. Methods. Patients with stage I-IIA SCLC undergoing surgery and adjuvant chemotherapy were extracted from the Surveillance, Epidemiology, and End Results database. Stage I-IIA, defined as T1-2N0M0, was recalculated according to the 8th AJCC TNM staging system. Propensity score matching (PSM) was conducted to identify the therapeutic impact of PORT. Univariate Cox hazards regression and least absolute shrinkage and selection operator regression were utilized for primary screening of prognostic variables for I-IIA SCLC disease. A nomogram to predict overall survival (OS) was constructed based on the multivariate Cox proportional hazards model, evaluated with area under the curve, calibration curve, and decision curve analysis, and validated with bootstrap resampling. Results. Our results demonstrated that compared with no PORT, PORT significantly prolonged the median OS (8.58 vs. 5.17 years, HR = 0.61 [0.39–0.96], P = 0.032 ) and median cancer-specific survival (11.33 vs. 8.08, HR = 0.47 [0.27–0.82], P = 0.0086 ) after PSM. The 5-year OS rate was 61.56% vs. 46.60%. Five variables including age at diagnosis, gender, T stage, surgical type, and PORT were elucidated to impact on prognosis and included in a nomogram to predict 3-/5-/10-year OS probability. The area under the curve values were 0.72, 0.71, and 0.81, respectively. The nomogram also exhibited satisfactory accuracy and clinical usefulness. Conclusion. PORT was verified to improve the OS of patients with T1-2N0M0 SCLC after surgery and chemotherapy. A prognostic nomogram was developed and validated for OS prediction for these patients.

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Development and Verification of the Hypoxia- and Immune-Associated Prognostic Signature for Pancreatic Ductal Adenocarcinoma

Cited by 38 publications

References 50 publications

Hallmark-guided subtypes of hepatocellular carcinoma for the identification of immune-related gene classifiers in the prediction of prognosis, treatment efficacy, and drug candidates

Hallmark-guided subtypes of hepatocellular carcinoma for the identification of immune-related gene classifiers in the prediction of prognosis, treatment efficacy, and drug candidates

Emerging Trends and Research Foci in Tumor Microenvironment of Pancreatic Cancer: A Bibliometric and Visualized Study

Additional Postoperative Radiotherapy Prolonged the Survival of Patients with I-IIA Small Cell Lung Cancer: Analysis of the SEER Database

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