Model of Pancreatic Cancer Prognosis Based on LncRNA Linked to Hypoxia

Abstract

Abstract: Objective The goal was to use hypoxia-associated LncRNAs to predict the prognosis of pancreatic cancer patients. Methods The TCGA database provided all of the transcriptome data and clinical information linked to pancreatic cancer. GSEA was used to identify hypoxia-associated genes, and co-expression was used to identify hypoxia-related LncRNAs.For the purpose of creating the prognostic model, prognostic-related hypoxic LncRNAs were filtered out using one-way and multifactorial Cox analyses. The predictive significance of hypoxia-associated LncRNA characteristics in pancreatic cancer was examined over time using survival curves and ROC curves. Ultimately, the expression of the distinctive LncRNAs was used to classify pancreatic cancer tumors, and the research confirmed that there was a strong correlation between the expression of these LncRNAs and pancreatic cancer. In order to identify the important hypoxia-associated LncRNAs with substantial prognostic value and research significance, the lasso regression model was further examined. Results A total of 29 of the differentially expressed hypoxia-associated LncRNAs were found to be potentially associated with prognosis by one-way Cox regression analysis. These 29 LncRNAs were then optimized by multifactorial Cox analysis to yield 6 distinctive LncRNAs influencing prognosis. The prognostic model survival curves created by the 6 LncRNAs also demonstrated that the low-risk group's prognosis was better than the high-risk group's, with a statistically significant difference between the two groups. statistically noteworthy. The prognostic model could be utilized as an independent prognostic factor, according to the independent prognostic analysis. Ultimately, four hypoxia-related LncRNAs with considerable predictive significance were obtained by further filtering and censoring the lasso regression model. Conclusion With the use of four hypoxia-related LncRNAs, we were able to effectively build a predictive model for pancreatic cancer in this work. This model is crucial for enhancing prognosis prediction and directing patients' individualized treatment. The four essential distinctive LncRNAs in this model could be unique markers for predicting pancreatic cancer prognosis.

Key words: pancreatic cancer, hypoxia related genes, LncRNA, prognosis

CLC Number:

R364.4

ZHENG Yan, HAN Li-hong, YAN Bin, LIN Cui-ying. Model of Pancreatic Cancer Prognosis Based on LncRNA Linked to Hypoxia[J]. ZHONGHUA YANGSHENG BAOJIAN, 2024, 42(7): 4-9.

References

[1] SIEGEL R L, MILLER K D, WAGLE N S, et al.Cancer Statistics, 2023[J]. CA Cancer J Clin,2023,73(1):17-48.
[2] SUNG H, FERLAY J, SIEGEL R L, et al.Global Cancer Statistics 2020: Globocan Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin,2021,71(3):209-249.
[3] MCGUIGAN A, KELLY P, TURKINGTON R C, et al.Pancreatic Cancer: A Review of Clinical Diagnosis, Epidemiology, Treatment and Outcomes[J]. World J Gastroenterol,2018,24(43):4846-4861.
[4] MARCHESE F, RAIMONDI I, HUARTE M.The Multidimensional Mechanisms of Long Noncoding Rna Function[J]. Genome biology,2017,18(1):206.
[5] BRIDGES M C, DAULAGALA A C, KOURTIDIS A.Lnccation: Lncrna Localization and Function[J]. J Cell Biol,2021,220(2):e202009045.
[6] STATELLO L, GUO C, CHEN L, et al.Gene Regulation by Long Non-Coding Rnas and Its Biological Functions[J]. Nature reviews Molecular cell biology,2021,22(2):96-118.
[7] ZHUO Z L, XIAN H P, SUN Y J, et al.Long Noncoding Rna Znfx1-As1 Promotes the Invasion and Proliferation of Gastric Cancer Cells by Regulating Lin28 and Capr1n1[J]. World J Gastroenterol,2022,28(34):4973-4992.
[8] DHANI N, FYLES A, HEDLEY D, et al.The Clinical Significance of Hypoxia in Human Cancers[J]. Semin Nucl Med,2015,45(2):110-121.
[9] BHANDARI V, HOEY C, LIU L, et al.Molecular Landmarks of Tumor Hypoxia across Cancer Types[J]. Nature genetics,2019,51(2):308-318.
[10] AHMAD A, NAWAZ M.Molecular Mechanism of VEGF and Its Role in Pathological Angiogenesis[J]. J Cell Biochem,2022,123(12):1938-1965.
[11] MA F, ZHANG B, JI S, et al.Hypoxic Macrophage-Derived Vegf Promotes Proliferation and Invasion of Gastric Cancer Cells[J]. Dig Dis Sci,2019,64(11):3154-3163.
[12] YANG Y, WANG X, ZHANG J, et al.Abnormal Phenotype of Nrf2 Is Associated with Poor Prognosis through Hypoxic/Vegf-a-Rap1b/Vegfr2 Pathway in Gastric Cancer[J]. Aging,2022,14(7):3293-3312.
[13] FREZZETTI D, GALLO M, MAIELLO M, et al.Vegf as a Potential Target in Lung Cancer[J]. Expert Opin Ther Targets,2017,21(10):959-966.
[14] MABETA P, STEENKAMP V.The Vegf/Vegfr Axis Revisited: Implications for Cancer Therapy[J]. Int J Mol Sci,2022,23(24):15585.
[15] GBD 2017 Pancreatic Cancer Collaborators. The Global, Regional, and National Burden of Pancreatic Cancer and Its Attributable Risk Factors in 195 Countries and Territories, 1990-2017: A Systematic Analysis for the Global Burden of Disease Study 2017BD 2017 Pancreatic Cancer Collaborators. The Global, Regional, and National Burden of Pancreatic Cancer and Its Attributable Risk Factors in 195 Countries and Territories, 1990-2017: A Systematic Analysis for the Global Burden of Disease Study 2017[J].Lancet Gastroenterol Hepatolo,2019,4(12):934-947.
[16] KLEIN A P.Pancreatic Cancer Epidemiology: Understanding the Role of Lifestyle and Inherited Risk Factors[J].Nat Rev Gastroenterol Hepatol,2021,18(7):493-502.
[17] WOOD L, CANTO M, JAFFEE E, et al.Pancreatic Cancer: Pathogenesis, Screening, Diagnosis, and Treatment[J]. Gastroenterology,2022,163(2):386-402.
[18] MENNERICH D, KUBAICHUK K, KIETZMANN T. Dubs, Hypoxia,Cancer[J]. Trends Cancer,2019,5(10):632-653.
[19] TAN Y T, LIN J F, LI T, et al.Lncrna-Mediated Posttranslational Modifications and Reprogramming of Energy Metabolism in Cancer[J]. Cancer Commun (Lond),2021,41(2):109-120.
[20] LI J, MENG H, BAI Y, et al.Regulation of Lncrna and Its Role in Cancer Metastasis[J]. Oncol Res,2016,23(5):205-217.