Integrated transcriptomics and proteomics analysis of the impact of iodine‑125 in hepatocellular carcinoma

Yang,Yang; Yang,Wei; Shen,Jie; Ding,Enci

doi:10.3892/mmr.2025.13431

Integrated transcriptomics and proteomics analysis of the impact of iodine‑125 in hepatocellular carcinoma

Authors:
- Yang Yang
- Wei Yang
- Jie Shen
- Enci Ding
View Affiliations

Affiliations: The First Central Clinical School, Tianjin Medical University, Tianjin 300000, P.R. China, Department of Cardiology, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan 450000, P.R. China, The First Central Clinical School, Tianjin Medical University, Tianjin 300000, P.R. China
Published online on: January 6, 2025 https://doi.org/10.3892/mmr.2025.13431
Article Number: 66
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Hepatocellular carcinoma (HCC) is a common cause of cancer‑related mortality and morbidity worldwide. While iodine‑125 (¹²⁵I) particle brachytherapy has been extensively used in the clinical treatment of various types of cancer, the precise mechanism underlying its effectiveness in treating HCC remains unclear. In the present study, MHCC‑97H cells were treated with ¹²⁵I, after which, cell viability and proliferation were assessed using Cell Counting Kit‑8, 5‑ethynyl‑2'‑deoxyuridine and colony formation assays, cell invasion and migration were evaluated using wound healing and Transwell assays, and cell apoptosis was determined using flow cytometry. Omics data were analyzed using Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and STRING analyses to observe the key genes that exhibited significant changes at the transcriptional and protein levels in MHCC‑97H cells treated with ¹²⁵I particles. Finally, the expression levels of key genes (GPNMB, C4BPA, CTH, H1‑0 and MT2A) were verified through reverse transcription quantitative PCR. Following treatment with ¹²⁵I, the proliferation, invasion and migration of MHCC‑97H cells were inhibited, and apoptosis was enhanced. The results of omics data analysis indicated that the biological behavior of MHCC‑97H cells treated with ¹²⁵I was related to the expression levels of CTH and MT2A genes. These findings indicated that intervention with ¹²⁵I radiation particles may induce changes in gene expression, potentially influencing alterations in biological characteristics. In conclusion, these insights may shed light on the underlying mechanisms of ¹²⁵I radiation particle therapy in HCC and offer novel targets for HCC treatment.

View Figures

View References

1	Tsuchiya N, Sawada Y, Endo I, Saito K, Uemura Y and Nakatsura T: Biomarkers for the early diagnosis of hepatocellular carcinoma. World J Gastroenterol. 21:10573–10583. 2015. View Article : Google Scholar : PubMed/NCBI
2	Wang W and Wei C: Advances in the early diagnosis of hepatocellular carcinoma. Genes Dis. 7:308–319. 2020. View Article : Google Scholar : PubMed/NCBI
3	Huang S, Cao Y, Wang R, Liu H, Wang T and Yang S: Feasibility of ¹²⁵I brachytherapy combined with arterial infusion chemotherapy in patients with advanced pancreatic cancer. Medicine (Baltimore). 102:e350332023. View Article : Google Scholar : PubMed/NCBI
4	Wang X and Wang D: Clinical analysis of ¹²⁵I seed implantation combined with epidermal growth factor receptor-tyrosine kinase inhibitors in advanced non-small cell lung cancer. J BUON. 26:1879–1886. 2021.PubMed/NCBI
5	Peng S, Yang QX, Zhang T, Lu MJ, Yang G, Liu ZY, Zhang R and Zhang FJ: Lobaplatin-TACE combined with radioactive ¹²⁵I seed implantation for treatment of primary hepatocellular carcinoma. Asian Pac J Cancer Prev. 15:5155–5160. 2014. View Article : Google Scholar : PubMed/NCBI
6	Sun H, Zhang M, Liu R, Liu Y, Hou Y and Wu C: Endovascular implantation of ¹²⁵I seed combined with transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma. Future Oncol. 14:1165–1176. 2018. View Article : Google Scholar : PubMed/NCBI
7	Brown ZJ, Tsilimigras DI, Ruff SM, Mohseni A, Kamel IR, Cloyd JM and Pawlik TM: Management of hepatocellular carcinoma: A review. JAMA Surg. 158:410–420. 2023. View Article : Google Scholar : PubMed/NCBI
8	Juaid N, Amin A, Abdalla A, Reese K, Alamri Z, Moulay M, Abdu S and Miled N: Anti-hepatocellular carcinoma biomolecules: molecular targets insights. Int J Mol. 22:107742021. View Article : Google Scholar
9	Li D, Wang WJ, Wang YZ, Wang YB and Li YL: Lobaplatin promotes 125I-induced apoptosis and inhibition of proliferation in hepatocellular carcinoma by upregulating PERK-eIF2α-ATF4-CHOP pathway. Cell Death Dis. 10:7442019. View Article : Google Scholar : PubMed/NCBI
10	Chelakkot C, Chelakkot VS, Shin Y and Song K: Modulating glycolysis to improve cancer therapy. Int J Mol Sci. 24:26062023. View Article : Google Scholar : PubMed/NCBI
11	Liu LX, Heng JH, Deng DX, Zhao H, Zheng ZY, Liao LD, Lin W, Xu XE, Li EM and Xu LY: Sulconazole induces panoptosis by triggering oxidative stress and inhibiting glycolysis to increase radiosensitivity in esophageal cancer. Mol Cell Proteomics. 22:1005512023. View Article : Google Scholar : PubMed/NCBI
12	Zheng J, Luo J, Zeng H, Guo L and Shao G: ¹²⁵I suppressed the Warburg effect viaregulating miR-338/PFKL axis in hepatocellular carcinoma. Biomed Pharmacother. 119:1094022019. View Article : Google Scholar : PubMed/NCBI
13	Wang H, Ma D, Wang C, Zhao S and Liu C: Triptolide Inhibits Invasion and Tumorigenesis of Hepatocellular Carcinoma MHCC-97H Cells Through NF-κB Signaling. Med Sci Monit. 22:1827–1836. 2016. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2 (−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Fujita M, Chen MM, Siwak DR, Sasagawa S, Oosawa-Tatsuguchi A, Arihiro K, Ono A, Miura R, Maejima K, Aikata H, et al: Proteo-genomic characterization of virus-associated liver cancers reveals potential subtypes and therapeutic targets. Nat Commun. 13:64812022. View Article : Google Scholar : PubMed/NCBI
16	Zhang W, Yang C, Hu Y, Yi K, Xiao W, Xu X and Chen Z: Comprehensive analysis of the correlation of the pan-cancer gene HAUS5 with prognosis and immune infiltration in liver cancer. Sci Rep. 13:24092023. View Article : Google Scholar : PubMed/NCBI
17	Zhou PY, Zhou C, Gan W, Tang Z, Sun BY, Huang JL, Liu G, Liu WR, Tian MX, Jiang XF, et al: Single-cell and spatial architecture of primary liver cancer. Commun Biol. 6:11812023. View Article : Google Scholar : PubMed/NCBI
18	Qiu Z, Yu C, Qiu X, Li Q, Li J, Chen Z, Chang S, Zhang S, Fan G and Wang S: Safety and Efficacy of CT-Guided Iodine-125 Brachytherapy for Portal Vein Tumor Thrombus in Hepatocellular Carcinoma. Acad Radiol. 30 (Suppl 1):S53–S60. 2023. View Article : Google Scholar : PubMed/NCBI
19	Saade M, Araujo de Souza G, Scavone C and Kinoshita PF: The Role of GPNMB in Inflammation. Front Immunol. 12:6747392021. View Article : Google Scholar : PubMed/NCBI
20	Xie R, Okita Y, Ichikawa Y, Fikry MA, Huynh Dam KT, Tran STP and Kato M: Role of the kringle-like domain in glycoprotein NMB for its tumorigenic potential. Cancer Sci. 110:2237–2246. 2019. View Article : Google Scholar : PubMed/NCBI
21	Chen L, Shan X, Wan X, Zha W and Fan R: HOMER3 promotes liver hepatocellular carcinoma cancer progression by -upregulating EZH2 and mediating miR-361/GPNMB axis. Pathol Res Pract. 254:1551502024. View Article : Google Scholar : PubMed/NCBI
22	Blom AM: A cluster of positively charged amino acids in the alpha-chain of C4b-binding protein (C4BP) is pivotal for the regulation of the complement system and the interaction with bacteria. Scand J Clin Lab Invest Suppl. 233:37–49. 2000.PubMed/NCBI
23	Blom AM: Structural and functional studies of complement inhibitor C4b-binding protein. Biochem Soc Trans. 30:978–982. 2002. View Article : Google Scholar : PubMed/NCBI
24	Feng G, Li J, Zheng M, Yang Z, Liu Y, Zhang S, Ye L, Zhang W and Zhang X: Hepatitis B virus X protein up-regulates C4b-binding protein α through activating transcription factor Sp1 in protection of hepatoma cells from complement attack. Oncotarget. 7:28013–28026. 2016. View Article : Google Scholar : PubMed/NCBI
25	Dong W, Xia Z, Chai Z, Qiu Z, Wang X, Yang Z, Wang J, Zhang T, Zhang Q and Jin J: Proteomic analysis of small extracellular vesicles from the plasma of patients with hepatocellular carcinoma. World J Surg Oncol. 20:3872022. View Article : Google Scholar : PubMed/NCBI
26	He X, Wang Y, Zhang W, Li H, Luo R, Zhou Y, Liao CL, Huang H, Lv X, Xie Z and He M: Screening differential expression of serum proteins in AFP-negative HBV-related hepatocellular carcinoma using iTRAQ-MALDI-MS/MS. Neoplasma. 61:17–26. 2014. View Article : Google Scholar : PubMed/NCBI
27	Kanda T, Jiang X and Yokosuka O: Androgen receptor signaling in hepatocellular carcinoma and pancreatic cancers. World J Gastroenterol. 20:9229–9236. 2014.PubMed/NCBI
28	Kohli A, Huang SL, Chang TC, Chao CC and Sun NK: H1.0 induces paclitaxel-resistance genes expression in ovarian cancer cells by recruiting GCN5 and androgen receptor. Cancer Sci. 113:2616–2626. 2022. View Article : Google Scholar : PubMed/NCBI
29	Pan Y, Ye S, Yuan D, Zhang J, Bai Y and Shao C: Hydrogen sulfide (H2S)/cystathionine γ-lyase (CSE) pathway contributes to the proliferation of hepatoma cells. Mutat Res. 763–764. 10–18. 2014.
30	Xiang J, Wu X, Liu W, Wei H, Zhu Z, Liu S, Song C, Gu Q, Wei S and Zhang Y: Bioinformatic analyzes and validation of cystathionine gamma-lyase as a prognostic biomarker and related to immune infiltrates in hepatocellular carcinoma. Heliyon. 9:e161522023. View Article : Google Scholar : PubMed/NCBI
31	Liu F, Li H, Chang H, Wang J and Lu J: Identification of hepatocellular carcinoma-associated hub genes and pathways by integrated microarray analysis. Tumori. 101:206–214. 2015. View Article : Google Scholar : PubMed/NCBI
32	Wang Y, Jiang T, Li Z, Lu L, Zhang R, Zhang D, Wang X and Tan J: Analysis of differentially co-expressed genes based on microarray data of hepatocellular carcinoma. Neoplasma. 64:216–221. 2017. View Article : Google Scholar : PubMed/NCBI
33	Datta J, Majumder S, Kutay H, Motiwala T, Frankel W, Costa R, Cha HC, MacDougald OA, Jacob ST and Ghoshal K: Metallothionein expression is suppressed in primary human hepatocellular carcinomas and is mediated through inactivation of CCAAT/enhancer binding protein alpha by phosphatidylinositol 3-kinase signaling cascade. Cancer Res. 67:2736–2746. 2007. View Article : Google Scholar : PubMed/NCBI
34	Park Y and Yu E: Expression of metallothionein-1 and metallothionein-2 as a prognostic marker in hepatocellular carcinoma. J Gastroenterol Hepatol. 28:1565–1572. 2013. View Article : Google Scholar : PubMed/NCBI
35	Tomasi ML, Cossu C, Spissu Y, Floris A, Ryoo M, Iglesias-Ara A, Wang Q, Pandol SJ, Bhowmick NA, Seki E, et al: S-adenosylmethionine and methylthioadenosine inhibit cancer metastasis by targeting microRNA 34a/b-methionine adenosyltransferase 2A/2B axis. Oncotarget. 8:78851–78869. 2017. View Article : Google Scholar : PubMed/NCBI