Top

Published in:

01-12-2022 | Gastric Cancer | Research

Single-cell sequencing analysis reveals gastric cancer microenvironment cells respond vastly different to oxidative stress

Authors: Weihua Yu, Guojun Chen, Jiafei Yan, Xianfa Wang, Yiping Zhu, Linghua Zhu

Published in: Journal of Translational Medicine | Issue 1/2022

Abstract

Gastric cancer is a common type of gastrointestinal malignant tumor in China. The mechanism of the development and progression of gastric cancer remains the continuing research focus. The tumor microenvironment plays an important role in the development and progression of tumors. The present study used single-cell sequencing data to characterize the microenvironment of gastric cancer, investigate the effects of oxidative stress on gastric cancer microenvironmental cells through the comparison between cancer tissue and normal tissue, and identify the key genes associated with gastric cancer patients’ survival. The results showed that compared with normal gastric tissue, gastric cancer tissue had a decreased oxidative stress response, weaker oxidative detoxification ability, and increased oxidative stress-induced cell death. In the different types of single cells of gastric cancer microenvironment, the oxidative stress response of T cell was increased, the ability of oxidative detoxification was enhanced, and the oxidative stress-induced cell death was exacerbate. Mucous cell showed the same trend as gastric cancer cells: decreased oxidative stress response, weak oxidative detoxification ability, and weakened oxidative stress-induced cell death. Moreover, TRIM62, MET, and HBA1, which were significantly associated with oxidative stress, may be biomarkers for the prognosis of gastric cancer. High expression of TRIM62 indicated a good prognosis, while MET and HBA1 indicated a poor prognosis, which will be confirmed by further clinical studies.

Available only for authorised users

Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric cancer: epidemiology, risk factors, classification, genomic characteristics and treatment strategies. Int J Mol Sci. 2020. https://doi.org/10.3390/ijms21114012].CrossRefPubMedPubMedCentral

Cao M, Li H, Sun D, He S, Lei L, Peng J, Chen W. Epidemiological trend analysis of gastric cancer in China from 2000 to 2019. Chin J Dig Surg. 2021;20:102–9.

Ji JF, Shan F. Comprehensive therapy of gastric carcinoma. Zhonghua Wai Ke Za Zhi. 2011;49:193–7.PubMed

Arneth B. Tumor Microenvironment. Medicina (Kaunas). 2019. https://doi.org/10.3390/medicina56010015].CrossRef

Oya Y, Hayakawa Y, Koike K. Tumor microenvironment in gastric cancers. Cancer Sci. 2020;111:2696–707. https://doi.org/10.1111/cas.14521].CrossRefPubMedPubMedCentral

Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA. Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res. 2014;2014: 149185. https://doi.org/10.1155/2014/149185].CrossRefPubMedPubMedCentral

Catalano V, Turdo A, Di Franco S, Dieli F, Todaro M, Stassi G. Tumor and its microenvironment: a synergistic interplay. Semin Cancer Biol. 2013;23:522–32. https://doi.org/10.1016/j.semcancer.2013.08.007].CrossRefPubMed

Kruk J, Aboul-Enein HY. Reactive oxygen and nitrogen species in carcinogenesis: implications of oxidative stress on the progression and development of several cancer types. Mini Rev Med Chem. 2017;17:904–19. https://doi.org/10.2174/1389557517666170228115324].CrossRefPubMed

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. J Proc Natl Acad Sci. 2005;102:15545–50. https://doi.org/10.1073/pnas.0506580102.CrossRef

10.

Slovin S, Carissimo A, Panariello F, Grimaldi A, Bouché V, Gambardella G, Cacchiarelli D. Single-cell RNA sequencing analysis: a step-by-step overview. Methods Mol Biol (Clifton, NJ). 2021;2284:343–65. https://doi.org/10.1007/978-1-0716-1307-8_19].CrossRef

11.

Sosa V, Moliné T, Somoza R, Paciucci R, Kondoh H, ME LL. Oxidative stress and cancer: an overview. Ageing Res Rev. 2013;12:376–90. https://doi.org/10.1016/j.arr.2012.10.004.CrossRefPubMed

12.

Klaunig JE. Oxidative stress and cancer. Curr Pharm Des. 2018;24:4771–8. https://doi.org/10.2174/1381612825666190215121712].CrossRefPubMed

13.

Dogan R, Guler EM, Kocyigit A, Çelik İ, Senturk E, Yenigun A, Tugrul S, Ozturan O. Are the oxidative stress levels in the tumor center and tumor boundary different from those in healthy tissue? Eur Arch Otorhinolaryngol. 2021. https://doi.org/10.1007/s00405-021-06749-x].CrossRefPubMed

14.

Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010;49:1603–16. https://doi.org/10.1016/j.freeradbiomed.2010.09.006].CrossRefPubMedPubMedCentral

15.

Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 2014;94:329–54. https://doi.org/10.1152/physrev.00040.2012].CrossRefPubMedPubMedCentral

16.

Huang T, Wang-Johanning F, Zhou F, Kallon H, Wei Y. MicroRNAs serve as a bridge between oxidative stress and gastric cancer (review). Int J Oncol. 2016;49:1791–800. https://doi.org/10.3892/ijo.2016.3686].CrossRefPubMed

17.

Ghafouri-Fard S, Shoorei H, Taheri M. Non-coding RNAs are involved in the response to oxidative stress. Biomed Pharmacother. 2020;127: 110228. https://doi.org/10.1016/j.biopha.2020.110228].CrossRefPubMed

18.

Gorrini C, Harris IS, Mak TW. Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov. 2013;12:931–47. https://doi.org/10.1038/nrd4002.CrossRefPubMed

19.

Roma-Rodrigues C, Mendes R, Baptista PV, Fernandes AR. Targeting tumor microenvironment for cancer therapy. Int J Mol Sci. 2019. https://doi.org/10.3390/ijms20040840].CrossRefPubMedPubMedCentral

20.

Zeng D, Li M, Zhou R, Zhang J, Sun H, Shi M, Bin J, Liao Y, Rao J, Liao W. Tumor microenvironment characterization in gastric cancer identifies prognostic and immunotherapeutically relevant gene signatures. Cancer Immunol Res. 2019;7:737–50. https://doi.org/10.1158/2326-6066.Cir-18-0436].CrossRefPubMed

21.

Choi JA, Kwon H, Cho H, Chung JY, Hewitt SM, Kim JH. ALDH1A2 is a candidate tumor suppressor gene in ovarian cancer. Cancers. 2019. https://doi.org/10.3390/cancers11101553.CrossRefPubMedPubMedCentral

22.

Auersperg N. The stem-cell profile of ovarian surface epithelium is reproduced in the oviductal fimbriae, with increased stem-cell marker density in distal parts of the fimbriae. Int J Gynecol Pathol. 2013;32:444–53. https://doi.org/10.1097/PGP.0b013e3182800ad5].CrossRefPubMed

23.

Huang F, Xiao H, Sun BL, Yang RG. Characterization of TRIM62 as a RING finger E3 ubiquitin ligase and its subcellular localization. Biochem Biophy Res Commun. 2013;432:208–13. https://doi.org/10.1016/j.bbrc.2013.02.012.CrossRef

24.

Chen M, Huang X, Li L, Huang M, Cai R, Liao X. A regulatory axis of circ_0008193/miR-1180–3p/TRIM62 suppresses proliferation, migration, invasion, and warburg effect in lung adenocarcinoma cells under hypoxia. Med Sci Monit. 2020;26: e922900. https://doi.org/10.12659/msm.922900].CrossRefPubMedPubMedCentral

25.

Terry S, Savagner P, Ortiz-Cuaran S, Mahjoubi L, Saintigny P, Thiery JP, Chouaib S. New insights into the role of EMT in tumor immune escape. Mol Oncol. 2017;11:824–46. https://doi.org/10.1002/1878-0261.12093].CrossRefPubMedPubMedCentral

26.

Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10:942–9. https://doi.org/10.1038/nm1093].CrossRefPubMed

27.

Maj T, Wang W, Crespo J, Zhang H, Wang W, Wei S, Zhao L, Vatan L, Shao I, Szeliga W, Lyssiotis C, Liu JR, Kryczek I, Zou W. Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor. Nat Immunol. 2017;18:1332–41. https://doi.org/10.1038/ni.3868].CrossRefPubMedPubMedCentral

28.

Zhang P, Yang M, Zhang Y, Xiao S, Lai X, Tan A, Du S, Li S. Dissecting the single-cell transcriptome network underlying gastric premalignant lesions and early gastric cancer. Cell Rep. 2019;27:1934-1947.e1935. https://doi.org/10.1016/j.celrep.2019.04.052].CrossRefPubMed

29.

Meyer AR, Goldenring JR. Injury, repair, inflammation and metaplasia in the stomach. J Physiol. 2018;596:3861–7. https://doi.org/10.1113/jp275512].CrossRefPubMedPubMedCentral

30.

Peng Z, Zhu Y, Wang Q, Gao J, Li Y, Li Y, Ge S, Shen L. Prognostic significance of MET amplification and expression in gastric cancer: a systematic review with meta-analysis. PLoS ONE. 2014;9: e84502. https://doi.org/10.1371/journal.pone.0084502].CrossRefPubMedPubMedCentral

31.

Moosavi F, Giovannetti E, Saso L, Firuzi O. HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers. Crit Rev Clin Lab Sci. 2019;56:533–66. https://doi.org/10.1080/10408363.2019.1653821].CrossRefPubMed

32.

Wu YP, Ke ZB, Lin F, Wen YA, Chen S, Li XD, Chen SH, Sun XL, Huang JB, Zheng QS, Xue XY, Wei Y, Xu N. Identification of key genes and pathways in castrate-resistant prostate cancer by integrated bioinformatics analysis. Pathol Res Pract. 2020;216: 153109. https://doi.org/10.1016/j.prp.2020.153109].CrossRefPubMed

33.

Nie K, Shi L, Wen Y, Pan J, Li P, Zheng Z, Liu F. Identification of hub genes correlated with the pathogenesis and prognosis of gastric cancer via bioinformatics methods. Miner Med. 2020;111:213–25. https://doi.org/10.23736/s0026-4806.19.06166-4].CrossRef

34.

Pandey P, Siddiqui MH, Behari A, Kapoor VK, Mishra K, Sayyed U, Tiwari RK, Shekh R, Bajpai P. Jab1-siRNA induces cell growth inhibition and cell cycle arrest in gall bladder cancer cells via targeting Jab1 signalosome. Anti Cancer Agents Med Chem. 2019;19:2019–33. https://doi.org/10.2174/1871520619666190725122400].CrossRef

35.

Pandey P, Khan F. Jab1 inhibition by methanolic extract of Moringa Oleifera leaves in cervical cancer cells: a potent targeted therapeutic approach. Nutr Cancer. 2021;73:2411–9. https://doi.org/10.1080/01635581.2020.1826989].CrossRefPubMed

36.

Teng L, Lu J. cMET as a potential therapeutic target in gastric cancer (review). Int J Mol Med. 2013;32:1247–54. https://doi.org/10.3892/ijmm.2013.1531].CrossRefPubMed

Title: Single-cell sequencing analysis reveals gastric cancer microenvironment cells respond vastly different to oxidative stress
Authors: Weihua Yu
Guojun Chen
Jiafei Yan
Xianfa Wang
Yiping Zhu
Linghua Zhu
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Gastric Cancer
Gastric Cancer
Published in: Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-022-03411-w

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2022

Targeting macrophages: a novel treatment strategy in solid tumors

Identifying CCR5 coreceptor populations permissive for HIV-1 entry and productive infection: implications for in vivo studies

Unilateral acute lung injury in pig: a promising animal model

Urinary exosomal hsa_circ_0001250 as a novel diagnostic biomarker of idiopathic membranous nephropathy

SPOP promotes cervical cancer progression by inducing the movement of PD-1 away from PD-L1 in spatial localization

Discovery of new therapeutic targets in ovarian cancer through identifying significantly non-mutated genes

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials