Application of Integrin Subunit Genes in Pancreatic Cancer and the Construction of a Prognosis Model

Overview

Journal J Gastrointest Oncol

Date 2024 Nov 18

PMID 39554585

Authors

Qiuwen Ye

Tao Zhou

Xin Liu

Dong Chen

Burong Yang

Tingdong Yu

Jing Tan

Affiliations

Soon will be listed here.

Abstract

Background: Pancreatic adenocarcinoma (PAAD) is a highly aggressive malignant tumor with a poor prognosis. Integrin subunit genes (ITGs) serve as biomarkers for various types of cancers; however, to date, no prognostic research has been conducted on the ITGs in PAAD. This study aims to fill this gap by investigating the role of ITGs in PAAD prognosis.

Methods: RNA-sequencing data, clinicopathological features, and survival information from The Cancer Genome Atlas (TCGA) database were sourced via GTEx. The GSE62452 data set was acquired from the Gene Expression Omnibus (GEO) database. A single-sample gene set enrichment analysis (ssGSEA) was first conducted to classify the PAAD samples from TCGA and GEO data sets with different ITG scores. A differential analysis was employed to identify the differentially expressed genes (DEGs) between the normal and PAAD samples, and between the high and low ITG score groups in both TCGA and GEO data sets.

Results: A total of 22 key differentially expressed ITGs (KDE-ITGs) were identified and enriched in eight Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, focal adhesion, and the extracellular matrix (ECM)-receptor interaction. A prognostic model comprising the eight KDE-ITGs was established. Additionally, 2,371 DEGs were found between the high- and low-risk groups, which were mainly enriched in the Gene Ontology (GO) terms of cell morphogenesis and cytokine production, and KEGG pathways such as necroptosis, lysosome, and ferroptosis. Further, the proportions of T cells and cluster of differentiation 8 (CD8) T cells, and the expression levels of immune checkpoints, such as cluster of differentiation 274 (CD274) and lymphocyte activating gene 3 (LAG3), differed significantly between the two risk groups.

Conclusions: The eight identified KDE-ITGs in PAAD were used to establish a new prognosis model, which might have clinical application, especially in immunotherapy.

References

Li Z, Zhou Y, Ding Y, Guo Q, Zhao L . Roles of integrin in tumor development and the target inhibitors. Chin J Nat Med. 2019; 17(4):241-251. DOI: 10.1016/S1875-5364(19)30028-7. View

Postow M, Callahan M, Wolchok J . Immune Checkpoint Blockade in Cancer Therapy. J Clin Oncol. 2015; 33(17):1974-82. PMC: 4980573. DOI: 10.1200/JCO.2014.59.4358. View

Ji T, Ma K, Chen L, Cao T . PADI1 contributes to EMT in PAAD by activating the ERK1/2-p38 signaling pathway. J Gastrointest Oncol. 2021; 12(3):1180-1190. PMC: 8261327. DOI: 10.21037/jgo-21-283. View

Mizrahi J, Surana R, Valle J, Shroff R . Pancreatic cancer. Lancet. 2020; 395(10242):2008-2020. DOI: 10.1016/S0140-6736(20)30974-0. View

Farooqui M, Bohrer L, Brady N, Chuntova P, Kemp S, Wardwell C . Epiregulin contributes to breast tumorigenesis through regulating matrix metalloproteinase 1 and promoting cell survival. Mol Cancer. 2015; 14:138. PMC: 4517352. DOI: 10.1186/s12943-015-0408-z. View

Gitlin J . Transcriptional regulation of ceruloplasmin gene expression during inflammation. J Biol Chem. 1988; 263(13):6281-7. View

Pan Z, Li L, Fang Q, Zhang Y, Hu X, Qian Y . Analysis of dynamic molecular networks for pancreatic ductal adenocarcinoma progression. Cancer Cell Int. 2019; 18:214. PMC: 6303882. DOI: 10.1186/s12935-018-0718-5. View

Tang N, Dou X, You X, Shi Q, Ke M, Liu G . Pan-cancer analysis of the oncogenic role of discs large homolog associated protein 5 (DLGAP5) in human tumors. Cancer Cell Int. 2021; 21(1):457. PMC: 8399833. DOI: 10.1186/s12935-021-02155-9. View

Han I, Jang J, Kwon W, Park T, Kim Y, Lee K . Ceruloplasmin as a prognostic marker in patients with bile duct cancer. Oncotarget. 2017; 8(17):29028-29037. PMC: 5438709. DOI: 10.18632/oncotarget.15995. View

10.

Socinski M, Pennell N, Davies K . Exon 14 Skipping Mutations in Non-Small-Cell Lung Cancer: An Overview of Biology, Clinical Outcomes, and Testing Considerations. JCO Precis Oncol. 2021; 5. PMC: 8140815. DOI: 10.1200/PO.20.00516. View

11.

Tsou A, Yang C, Huang C, Yu R, Lee Y, Chang C . Identification of a novel cell cycle regulated gene, HURP, overexpressed in human hepatocellular carcinoma. Oncogene. 2003; 22(2):298-307. DOI: 10.1038/sj.onc.1206129. View

12.

Brzozowska E, Deshmukh S . Integrin Alpha v Beta 6 (αvβ6) and Its Implications in Cancer Treatment. Int J Mol Sci. 2022; 23(20). PMC: 9603893. DOI: 10.3390/ijms232012346. View

13.

Patente T, Pinho M, Oliveira A, Evangelista G, Bergami-Santos P, Barbuto J . Human Dendritic Cells: Their Heterogeneity and Clinical Application Potential in Cancer Immunotherapy. Front Immunol. 2019; 9:3176. PMC: 6348254. DOI: 10.3389/fimmu.2018.03176. View

14.

Xu J, Lu W . FAM83A exerts tumor‑suppressive roles in cervical cancer by regulating integrins. Int J Oncol. 2020; 57(2):509-521. PMC: 7307588. DOI: 10.3892/ijo.2020.5078. View

15.

Chen J, Zhao J, Xie Z . Integrin-mediated cancer progression as a specific target in clinical therapy. Biomed Pharmacother. 2022; 155:113745. DOI: 10.1016/j.biopha.2022.113745. View

16.

Sun Q, Dong X, Shang Y, Sun F, Niu J, Li F . Integrin αvβ6 predicts poor prognosis and promotes resistance to cisplatin in hilar cholangiocarcinoma. Pathol Res Pract. 2020; 216(7):153022. DOI: 10.1016/j.prp.2020.153022. View

17.

Liu F, Wu Q, Dong Z, Liu K . Integrins in cancer: Emerging mechanisms and therapeutic opportunities. Pharmacol Ther. 2023; 247:108458. DOI: 10.1016/j.pharmthera.2023.108458. View

18.

Senra Varela A, Lopez Saez J, Quintela Senra D . Serum ceruloplasmin as a diagnostic marker of cancer. Cancer Lett. 1998; 121(2):139-45. DOI: 10.1016/s0304-3835(97)00340-6. View

19.

Zhang Y, Xia M, Jin K, Wang S, Wei H, Fan C . Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities. Mol Cancer. 2018; 17(1):45. PMC: 5817860. DOI: 10.1186/s12943-018-0796-y. View

20.

Huang M, Lin C, Chen J . [Integrin activation, focal adhesion maturation and tumor metastasis]. Sheng Li Xue Bao. 2021; 73(2):151-159. View