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Cancer Cell International
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Open Access 01-12-2024 | Research

Analysis and experimental validation of disulfidptosis related genes solute carrier family 3 member 2 (SLC3A2) in endometrial cancer

Authors: Bo Wang, Wantong Wang, Yuting Wang, Xin Wen, Zihao Wang, Hongrui Leng, Fanfei Kong, Xiaoxin Ma

Published in: Cancer Cell International | Issue 1/2024

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Abstract

Disulfidptosis, a novel cell death paradigm triggered by disulfide stress, remains underexplored, particularly its implications for endometrial cancer (EC). This study focused on the prognostic significance of disulfidptosis-related genes (DRGs) in EC, highlighting the pivotal role of SLC3A2. To predict EC patient outcomes, we developed a model centered on DRGs, employing LASSO-Cox regression for its construction. The model revealed a strong correlation between DRG risk score, gene set enrichment analysis (GSEA), single-sample GSEA (ssGSEA), clinical characteristics, the tumor microenvironment (TME), and the response to immunotherapy. Key genes were pinpointed using random forest maps. To establish SLC3A2's oncogenic effects in EC, we conducted comprehensive studies including apoptosis, cell cycle, TRANSWELL, CCK-8, and tumor xenograft assays. SLC3A2 expression was further confirmed via qRT-PCR. The impact of SLC3A2 on EC's malignant behavior was corroborated through both in vitro and in vivo experiments.
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Literature
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRefPubMed
2.
Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. Lancet. 2022;399(10333):1412–28.PubMedCrossRef
3.
Nagy P. Kinetics and mechanisms of thiol-disulfide exchange covering direct substitution and thiol oxidation-mediated pathways. Antioxid Redox Signal. 2013;18(13):1623–41.PubMedPubMedCentralCrossRef
4.
5.
Liu X, Nie L, Zhang Y, Yan Y, Wang C, Colic M, Olszewski K, Horbath A, Chen X, Lei G, et al. Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. Nat Cell Biol. 2023;25(3):404–14.PubMedPubMedCentralCrossRef
6.
7.
8.
Zhong Z, Zhang C, Ni S, Ma M, Zhang X, Sang W, Lv T, Qian Z, Yi C, Yu B. NFATc1-mediated expression of SLC7A11 drives sensitivity to TXNRD1 inhibitors in osteoclast precursors. Redox Biol. 2023;63:102711.PubMedPubMedCentralCrossRef
9.
Wang T, Guo K, Zhang D, Wang H, Yin J, Cui H, Wu W. Disulfidptosis classification of hepatocellular carcinoma reveals correlation with clinical prognosis and immune profile. Int Immunopharmacol. 2023;120:110368.PubMedCrossRef
10.
Qi C, Ma J, Sun J, Wu X, Ding J. The role of molecular subtypes and immune infiltration characteristics based on disulfidptosis-associated genes in lung adenocarcinoma. Aging (Albany NY). 2023;15(11):5075–95.PubMed
11.
Chen H, Yang W, Li Y, Ma L, Ji Z. Leveraging a disulfidptosis-based signature to improve the survival and drug sensitivity of bladder cancer patients. Front Immunol. 2023;14:1198878.PubMedPubMedCentralCrossRef
12.
Shin CS, Mishra P, Watrous JD, Carelli V, D’Aurelio M, Jain M, Chan DC. The glutamate/cystine xCT antiporter antagonizes glutamine metabolism and reduces nutrient flexibility. Nat Commun. 2017;8:15074.PubMedPubMedCentralCrossRef
13.
Koppula P, Zhang Y, Shi J, Li W, Gan B. The glutamate/cystine antiporter SLC7A11/xCT enhances cancer cell dependency on glucose by exporting glutamate. J Biol Chem. 2017;292(34):14240–9.PubMedPubMedCentralCrossRef
14.
Goji T, Takahara K, Negishi M, Katoh H. Cystine uptake through the cystine/glutamate antiporter xCT triggers glioblastoma cell death under glucose deprivation. J Biol Chem. 2017;292(48):19721–32.PubMedPubMedCentralCrossRef
15.
Liu X, Olszewski K, Zhang Y, Lim EW, Shi J, Zhang X, Zhang J, Lee H, Koppula P, Lei G, et al. Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. Nat Cell Biol. 2020;22(4):476–86.PubMedPubMedCentralCrossRef
16.
Simon N, Friedman J, Hastie T, Tibshirani R. Regularization paths for Cox’s proportional hazards model via coordinate descent. J Stat Softw. 2011;39(5):1–13.PubMedPubMedCentralCrossRef
17.
Yoshihara K, Shahmoradgoli M, Martínez E, Vegesna R, Kim H, Torres-Garcia W, Treviño V, Shen H, Laird PW, Levine DA, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612.PubMedCrossRef
18.
Malta TM, Sokolov A, Gentles AJ, Burzykowski T, Poisson L, Weinstein JN, Kamińska B, Huelsken J, Omberg L, Gevaert O, et al. Machine learning identifies stemness features associated with oncogenic dedifferentiation. Cell. 2018;173(2):338-354.e315.PubMedPubMedCentralCrossRef
19.
Cai L, Hu C, Yu S, Liu L, Zhao J, Zhao Y, Lin F, Du X, Yu Q, Xiao Q. Identification of EMT-related gene signatures to predict the prognosis of patients with endometrial cancer. Front Genet. 2020;11:582274.PubMedPubMedCentralCrossRef
20.
Liu J, Li S, Feng G, Meng H, Nie S, Sun R, Yang J, Cheng W. Nine glycolysis-related gene signature predicting the survival of patients with endometrial adenocarcinoma. Cancer Cell Int. 2020;20:183.PubMedPubMedCentralCrossRef
21.
Liu J, Mei J, Li S, Wu Z, Zhang Y. Establishment of a novel cell cycle-related prognostic signature predicting prognosis in patients with endometrial cancer. Cancer Cell Int. 2020;20:329.PubMedPubMedCentralCrossRef
22.
23.
24.
25.
Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K. Body fatness and cancer-viewpoint of the IARC working group. N Engl J Med. 2016;375(8):794–8.PubMedPubMedCentralCrossRef
26.
Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–21.PubMedCrossRef
27.
Weiderpass E, Antoine J, Bray FI, Oh JK, Arbyn M. Trends in corpus uteri cancer mortality in member states of the European Union. Eur J Cancer. 2014;50(9):1675–84.PubMedCrossRef
28.
Zhao D, Meng Y, Dian Y, Zhou Q, Sun Y, Le J, Zeng F, Chen X, He Y, Deng G. Molecular landmarks of tumor disulfidptosis across cancer types to promote disulfidptosis-target therapy. Redox Biol. 2023;68:102966.PubMedPubMedCentralCrossRef
29.
30.
Hadian K, Stockwell BR. The therapeutic potential of targeting regulated non-apoptotic cell death. Nat Rev Drug Discov. 2023;22(9):723–42.PubMedCrossRef
31.
Yan Y, Teng H, Hang Q, Kondiparthi L, Lei G, Horbath A, Liu X, Mao C, Wu S, Zhuang L, et al. SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells. Nat Commun. 2023;14(1):3673.PubMedPubMedCentralCrossRef
32.
Wang Z, Chen X, Zhang J, Chen X, Peng J, Huang W. Based on disulfidptosis-related glycolytic genes to construct a signature for predicting prognosis and immune infiltration analysis of hepatocellular carcinoma. Front Immunol. 2023;14:1204338.PubMedPubMedCentralCrossRef
33.
Xue W, Qiu K, Dong B, Guo D, Fu J, Zhu C, Niu Z. Disulfidptosis-associated long non-coding RNA signature predicts the prognosis, tumor microenvironment, and immunotherapy and chemotherapy options in colon adenocarcinoma. Cancer Cell Int. 2023;23(1):218.PubMedPubMedCentralCrossRef
34.
Wang Y, Xu Y, Liu C, Yuan C, Zhang Y. Identification of disulfidptosis-related subgroups and prognostic signatures in lung adenocarcinoma using machine learning and experimental validation. Front Immunol. 2023;14:1233260.PubMedPubMedCentralCrossRef
35.
Zhang HB, Pan JY, Zhu T. A disulfidptosis-related lncRNA prognostic model to predict survival and response to immunotherapy in lung adenocarcinoma. Front Pharmacol. 2023;14:1254119.PubMedPubMedCentralCrossRef
36.
Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, Porta-Pardo E, Gao GF, Plaisier CL, Eddy JA, et al. The Immune Landscape of Cancer. Immunity. 2018;48(4):812-830.e814.PubMedPubMedCentralCrossRef
37.
Liang J, Wang X, Yang J, Sun P, Sun J, Cheng S, Liu J, Ren Z, Ren M. Identification of disulfidptosis-related subtypes, characterization of tumor microenvironment infiltration, and development of a prognosis model in breast cancer. Front Immunol. 2023;14:1198826.PubMedPubMedCentralCrossRef
38.
Liao Z, Cheng Y, Zhang H, Jin X, Sun H, Wang Y, Yan J. A novel prognostic signature and immune microenvironment characteristics associated with disulfidptosis in papillary thyroid carcinoma based on single-cell RNA sequencing. Front Cell Dev Biol. 2023;11:1308352.PubMedPubMedCentralCrossRef
39.
Visvader JE, Lindeman GJ. Cancer stem cells: current status and evolving complexities. Cell Stem Cell. 2012;10(6):717–28.PubMedCrossRef
40.
Atashzar MR, Baharlou R, Karami J, Abdollahi H, Rezaei R, Pourramezan F, Zoljalali Moghaddam SH. Cancer stem cells: a review from origin to therapeutic implications. J Cell Physiol. 2020;235(2):790–803.PubMedCrossRef
41.
Fillon M. Adding immunotherapy to chemotherapy improves survival for endometrial cancer patients. CA Cancer J Clin. 2023;73(5):445–7.PubMedCrossRef
42.
Polak P, Fu L, Foulkes WD. PD-1 and PD-L1 blockade plus chemotherapy in endometrial cancer. N Engl J Med. 2023;389(9):866.PubMedCrossRef
43.
Rochigneux P, Garcia AJ, Chanez B, Madroszyk A, Olive D, Garon EB. Medical treatment of lung cancer: can immune cells predict the response? A systematic review. Front Immunol. 2020;11:1036.PubMedPubMedCentralCrossRef
44.
Susumu N, Sagae S, Udagawa Y, Niwa K, Kuramoto H, Satoh S, Kudo R. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study. Gynecol Oncol. 2008;108(1):226–33.PubMedCrossRef
45.
Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2006;24(1):36–44.PubMedCrossRef
46.
El Ansari R, Craze ML, Diez-Rodriguez M, Nolan CC, Ellis IO, Rakha EA, Green AR. The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes. Br J Cancer. 2018;118(8):1115–22.PubMedPubMedCentralCrossRef
47.
Liu D, An M, Wen G, Xing Y, Xia P. Both in situ and circulating SLC3A2 could be used as prognostic markers for human lung squamous cell carcinoma and lung adenocarcinoma. Cancers. 2022;14(21):5191.PubMedPubMedCentralCrossRef
Metadata
Title
Analysis and experimental validation of disulfidptosis related genes solute carrier family 3 member 2 (SLC3A2) in endometrial cancer
Authors
Bo Wang
Wantong Wang
Yuting Wang
Xin Wen
Zihao Wang
Hongrui Leng
Fanfei Kong
Xiaoxin Ma
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2024
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-024-03560-6

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