Effective Oxygen Metabolism-based Prognostic Signature for Colorectal Cancer

Overview

Journal Front Oncol

Specialty Oncology

Date 2023 Feb 27

PMID 36845724

Authors

Yonghui Yuan

Zhong-Guo Zhang

Bin Ma

Pengfei Ji

Shiyang Ma

Xun Qi

Affiliations

Soon will be listed here.

Abstract

Backgroud: Oxygen metabolism is an important factor affecting the development of tumors, but its roles and clinical value in Colorectal cancer are not clear. We developed an oxygen metabolism (OM) based prognostic risk model for colorectal cancer and explored the role of OM genes in cancer.

Methods: Gene expression and clinical data obtained from The Cancer Genome Atlas, Clinical Proteomic Tumor Analysis Consortium databases were consider as discovery and validation cohort, respectively. The prognostic model based on differently expressed OM genes between tumor and GTEx normal colorectal tissues were constructed in discovery cohort and validated in validation cohort. The Cox proportional hazards analysis was used to test clinical independent. Upstream and downstream regulatory relationships and interaction molecules are used to clarify the roles of prognostic OM genes in colorectal cancer.

Results: A total of 72 common differently expressed OM genes were detected in the discovery and validation set. A five-OM gene prognostic model including , , , and was established and validated. Risk score determined by the model was an independent prognostic according to routine clinical factors. Besides, the role of prognostic OM genes involves transcriptional regulation of MYC and STAT3, and downstream cell stress and inflammatory response pathways.

Conclusions: We developed a five-OM gene prognostic model and study the unique roles of oxygen metabolism in of colorectal cancer.

Citing Articles

Landscape of unconventional γδ T cell subsets in cancer.

Azimnasab-Sorkhabi P, Soltani-Asl M, Soleiman Ekhtiyari M, Kfoury Junior J Mol Biol Rep. 2024; 51(1):238.

PMID: 38289417 DOI: 10.1007/s11033-024-09267-1.

SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification.

Wang H, Ma X, Li S, Ni X Aging (Albany NY). 2023; 15(22):13150-13162.

PMID: 37993256 PMC: 10713414. DOI: 10.18632/aging.205227.

References

Zeng H, Xu Y, Xu S, Jin L, Shen Y, Rajan K . Construction and Analysis of a Colorectal Cancer Prognostic Model Based on N6-Methyladenosine-Related lncRNAs. Front Cell Dev Biol. 2021; 9:698388. PMC: 8417314. DOI: 10.3389/fcell.2021.698388. View

Pavlova N, Thompson C . The Emerging Hallmarks of Cancer Metabolism. Cell Metab. 2016; 23(1):27-47. PMC: 4715268. DOI: 10.1016/j.cmet.2015.12.006. View

Edwards B, Ward E, Kohler B, Eheman C, Zauber A, Anderson R . Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 2009; 116(3):544-73. PMC: 3619726. DOI: 10.1002/cncr.24760. View

Jauhiainen S, Laakkonen J, Ketola K, Toivanen P, Nieminen T, Ninchoji T . Axon Guidance-Related Factor FLRT3 Regulates VEGF-Signaling and Endothelial Cell Function. Front Physiol. 2019; 10:224. PMC: 6423482. DOI: 10.3389/fphys.2019.00224. View

Keum N, Giovannucci E . Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019; 16(12):713-732. DOI: 10.1038/s41575-019-0189-8. View

Liu C, Wang T, Yang J, Zhang J, Wei S, Guo Y . Distant Metastasis Pattern and Prognostic Prediction Model of Colorectal Cancer Patients Based on Big Data Mining. Front Oncol. 2022; 12:878805. PMC: 9074728. DOI: 10.3389/fonc.2022.878805. View

Qi L, Chen L, Li Y, Qin Y, Pan R, Zhao W . Critical limitations of prognostic signatures based on risk scores summarized from gene expression levels: a case study for resected stage I non-small-cell lung cancer. Brief Bioinform. 2015; 17(2):233-42. DOI: 10.1093/bib/bbv064. View

Kohne C . Successes and limitations of targeted cancer therapy in colon cancer. Prog Tumor Res. 2014; 41:36-50. DOI: 10.1159/000356436. View

Nguyen A, Wu Y, Lin E . STAT3 and sphingosine-1-phosphate in inflammation-associated colorectal cancer. World J Gastroenterol. 2014; 20(30):10279-87. PMC: 4130835. DOI: 10.3748/wjg.v20.i30.10279. View

10.

Wang S, Sun Y . The IL-6/JAK/STAT3 pathway: potential therapeutic strategies in treating colorectal cancer (Review). Int J Oncol. 2014; 44(4):1032-40. DOI: 10.3892/ijo.2014.2259. View

11.

Maeda K, Chung Y, Ogawa Y, Takatsuka S, Kang S, Ogawa M . Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer. 1996; 77(5):858-63. DOI: 10.1002/(sici)1097-0142(19960301)77:5<858::aid-cncr8>3.0.co;2-a. View

12.

Jacobsen J, Rasmuson T, Grankvist K, Ljungberg B . Vascular endothelial growth factor as prognostic factor in renal cell carcinoma. J Urol. 1999; 163(1):343-7. View

13.

Kang S, Yu M, Park K, Chi S, Park D, Chung Y . Activated STAT3 regulates hypoxia-induced angiogenesis and cell migration in human glioblastoma. Neurosurgery. 2010; 67(5):1386-95. DOI: 10.1227/NEU.0b013e3181f1c0cd. View

14.

Mei Y, Chen M, Liang H, Ma L . A four-gene signature predicts survival and anti-CTLA4 immunotherapeutic responses based on immune classification of melanoma. Commun Biol. 2021; 4(1):383. PMC: 7985195. DOI: 10.1038/s42003-021-01911-x. View

15.

Hockel M, Knoop C, Schlenger K, Vorndran B, Baussmann E, Mitze M . Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol. 1993; 26(1):45-50. DOI: 10.1016/0167-8140(93)90025-4. View

16.

Bekeschus S, Liebelt G, Menz J, Singer D, Wende K, Schmidt A . Cell cycle-related genes associate with sensitivity to hydrogen peroxide-induced toxicity. Redox Biol. 2022; 50:102234. PMC: 8783094. DOI: 10.1016/j.redox.2022.102234. View

17.

Pendas-Franco N, Garcia J, Pena C, Valle N, Palmer H, Heinaniemi M . DICKKOPF-4 is induced by TCF/beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1alpha,25-dihydroxyvitamin D3. Oncogene. 2008; 27(32):4467-77. DOI: 10.1038/onc.2008.88. View

18.

Ratcliffe P . Oxygen sensing and hypoxia signalling pathways in animals: the implications of physiology for cancer. J Physiol. 2013; 591(8):2027-42. PMC: 3634517. DOI: 10.1113/jphysiol.2013.251470. View

19.

Yang C, Zhang Y, Xu X, Li W . Molecular subtypes based on DNA methylation predict prognosis in colon adenocarcinoma patients. Aging (Albany NY). 2019; 11(24):11880-11892. PMC: 6949097. DOI: 10.18632/aging.102492. View

20.

Wong K, Ching Ngai S, Chan K, Lee L, Goh B, Chuah L . Curcumin Nanoformulations for Colorectal Cancer: A Review. Front Pharmacol. 2019; 10:152. PMC: 6412150. DOI: 10.3389/fphar.2019.00152. View