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基于缺氧肿瘤微环境相关基因构建和验证胰腺癌预后模型。

Construction and validation of a pancreatic cancer prognostic model based on genes related to the hypoxic tumor microenvironment.

机构信息

Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China.

出版信息

World J Gastroenterol. 2024 Sep 28;30(36):4057-4070. doi: 10.3748/wjg.v30.i36.4057.

DOI:10.3748/wjg.v30.i36.4057
PMID:39351249
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11439118/
Abstract

BACKGROUND

Pancreatic cancer is one of the most lethal malignancies, characterized by poor prognosis and low survival rates. Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy, often failing to capture the complexity of the disease. The hypoxic tumor microenvironment has been recognized as a significant factor influencing cancer progression and resistance to treatment. This study aims to develop a prognostic model based on key hypoxia-related molecules to enhance prediction accuracy for patient outcomes and to guide more effective treatment strategies in pancreatic cancer.

AIM

To develop and validate a prognostic model for predicting outcomes in patients with pancreatic cancer using key hypoxia-related molecules.

METHODS

This pancreatic cancer prognostic model was developed based on the expression levels of the hypoxia-associated genes , , and . The results were validated in an independent dataset. This study also examined the correlations between the model risk score and various clinical features, components of the immune microenvironment, chemotherapeutic drug sensitivity, and metabolism-related pathways. Real-time quantitative PCR verification was conducted to confirm the differential expression of the target genes in hypoxic and normal pancreatic cancer cell lines.

RESULTS

The prognostic model demonstrated significant predictive value, with the risk score showing a strong correlation with clinical features: It was significantly associated with tumor grade (G) ( < 0.01), moderately associated with tumor stage (T) ( < 0.05), and significantly correlated with residual tumor (R) status ( < 0.01). There was also a significant negative correlation between the risk score and the half-maximal inhibitory concentration of some chemotherapeutic drugs. Furthermore, the risk score was linked to the enrichment of metabolism-related pathways in pancreatic cancer.

CONCLUSION

The prognostic model based on hypoxia-related genes effectively predicts pancreatic cancer outcomes with improved accuracy over traditional factors and can guide treatment selection based on risk assessment.

摘要

背景

胰腺癌是最致命的恶性肿瘤之一,其预后差,生存率低。传统的胰腺癌预后因素提供的预测准确性不足,往往无法捕捉疾病的复杂性。缺氧肿瘤微环境已被认为是影响癌症进展和治疗耐药性的重要因素。本研究旨在开发一种基于关键缺氧相关分子的预后模型,以提高对患者结局的预测准确性,并指导胰腺癌更有效的治疗策略。

目的

利用关键缺氧相关分子开发和验证用于预测胰腺癌患者结局的预后模型。

方法

本研究基于缺氧相关基因、和的表达水平开发了胰腺癌预后模型。在独立数据集进行验证。本研究还检查了模型风险评分与各种临床特征、免疫微环境成分、化疗药物敏感性和代谢相关途径之间的相关性。通过实时定量 PCR 验证证实了目标基因在缺氧和正常胰腺癌细胞系中的差异表达。

结果

该预后模型显示出显著的预测价值,风险评分与临床特征具有很强的相关性:与肿瘤分级(G)显著相关(<0.01),与肿瘤分期(T)中度相关(<0.05),与残留肿瘤(R)状态显著相关(<0.01)。风险评分与某些化疗药物的半最大抑制浓度之间也存在显著负相关。此外,风险评分与胰腺癌中代谢相关途径的富集有关。

结论

基于缺氧相关基因的预后模型可有效预测胰腺癌结局,其准确性优于传统因素,可根据风险评估指导治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11439118/d61bdbc92d27/WJG-30-4057-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11439118/78727a3e167e/WJG-30-4057-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11439118/33c3bad1e579/WJG-30-4057-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11439118/d61bdbc92d27/WJG-30-4057-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11439118/b91b4f1ffe8b/WJG-30-4057-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11439118/2d29345646a4/WJG-30-4057-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11439118/a12bc0690bb5/WJG-30-4057-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11439118/3031e5aeefd1/WJG-30-4057-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11439118/78727a3e167e/WJG-30-4057-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11439118/33c3bad1e579/WJG-30-4057-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11439118/d61bdbc92d27/WJG-30-4057-g008.jpg

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