Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Typ-2-Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Häufige urologisch-sexualmedizinische Themen in der Praxis sind das Thema des MMW-Webinars am 5. Juni von 17.30 bis 19 Uhr. Konkret geht es um die Frage, wann bei Harnwegsinfektionen auf Antibiotika verzichtet werden kann, und um ein Update zur Therapie von Libido- und Potenzstörungen des Mannes. Der dritte Vortrag behandelt sexuell übertragbare Krankheiten. Stellen Sie Ihre Fragen an die Experten und sammeln Sie 2 CME-Punkte. Jetzt gleich anmelden!
Erweiterte Suche
Anmelden
nach oben
Inflammation Research

04.05.2024 | Original Research Paper

Identification of diagnostic markers related to inflammatory response and cellular senescence in endometriosis using machine learning and in vitro experiment

verfasst von: Pusheng Yang, Yaxin Miao, Tao Wang, Jing Sun

Erschienen in: Inflammation Research

Einloggen, um Zugang zu erhalten

Abstract

Objective

To understand the association between chronic inflammation, cellular senescence, and immunological infiltration in endometriosis.

Methods

Datasets from GEO comprising 108 endometriosis and 97 healthy human samples and the human endometrial stromal cell. Differentially expressed genes were identified using Limma and WGCNA. Inflammatory response-related subtypes were constructed using consensus clustering analysis. The CIBERSORT algorithm and correlation analyses assessed immune cell infiltration. LASSO, SVM-RFE, and RF identified diagnostic genes. Functional enrichment analysis and multifactor regulatory networks established functional effects. Nomograms, internal and external validations, and in vitro experiments validated the diagnostic genes.

Results

Inflammatory response subtypes were highly correlated with the immune activities of B and NK cells. Sixteen genes were associated with inflammatory response and cellular senescence and six diagnostic genes (NLK, RAD51, TIMELESS, TBX3, MET, and BTG3) were identified. The six diagnostic gene models had an area under the curve of 0.828 and their expression was significantly downregulated in endometriosis samples. Low expression of NLK and BTG3 promoted the proliferation, migration, and invasion of endometriotic cells.

Conclusions

Inflammatory response subtypes were successfully constructed for endometriosis. Six diagnostic genes related to inflammatory response and cellular senescence were identified and validated. Our study provides novel insights for inflammatory response in endometriosis and markers for endometriosis diagnosis and treatment.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
2.
de Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet. 2010;376:730–8.PubMedCrossRef
3.
Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis. BMJ. 2022;379: e070750.PubMedCrossRef
4.
Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet. 2021;397:839–52.PubMedCrossRef
5.
Vercellini P, Vigano P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10:261–75.PubMedCrossRef
6.
Saunders PTK, Horne AW. Endometriosis: Etiology, pathobiology, and therapeutic prospects. Cell. 2021;184:2807–24.PubMedCrossRef
7.
Retrograde menstruation. Lancet. 1983;2:25–6.
8.
Symons LK, Miller JE, Kay VR, Marks RM, Liblik K, Koti M, et al. The immunopathophysiology of endometriosis. Trends Mol Med. 2018;24:748–62.PubMedCrossRef
9.
Zhang T, De Carolis C, Man GCW, Wang CC. The link between immunity, autoimmunity and endometriosis: a literature update. Autoimmun Rev. 2018;17:945–55.PubMedCrossRef
10.
Montagna P, Capellino S, Villaggio B, Remorgida V, Ragni N, Cutolo M, et al. Peritoneal fluid macrophages in endometriosis: correlation between the expression of estrogen receptors and inflammation. Fertil Steril. 2008;90:156–64.PubMedCrossRef
11.
Lousse JC, Van Langendonckt A, Gonzalez-Ramos R, Defrere S, Renkin E, Donnez J. Increased activation of nuclear factor-kappa B (NF-kappaB) in isolated peritoneal macrophages of patients with endometriosis. Fertil Steril. 2008;90:217–20.PubMedCrossRef
12.
Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E. From discoveries in ageing research to therapeutics for healthy ageing. Nature. 2019;571:183–92.PubMedPubMedCentralCrossRef
13.
Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, et al. Cellular senescence: defining a path forward. Cell. 2019;179:813–27.PubMedCrossRef
14.
15.
Zhu X, Chen Z, Shen W, Huang G, Sedivy JM, Wang H, et al. Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention. Signal Transduct Target Ther. 2021;6:245.PubMedPubMedCentralCrossRef
16.
Li X, Li C, Zhang W, Wang Y, Qian P, Huang H. Inflammation and aging: signaling pathways and intervention therapies. Signal Transduct Target Ther. 2023;8:239.PubMedPubMedCentralCrossRef
17.
Sayed N, Huang Y, Nguyen K, Krejciova-Rajaniemi Z, Grawe AP, Gao T, et al. An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging. Nat Aging. 2021;1:598–615.PubMedPubMedCentralCrossRef
18.
Munoz-Espin D, Serrano M. Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol. 2014;15:482–96.PubMedCrossRef
19.
Yang P, Lu J, Zhang P, Zhang S. Comprehensive analysis of prognosis and immune landscapes based on lipid-metabolism- and ferroptosis-associated signature in uterine corpus endometrial carcinoma. Diagnostics (Basel). 2023;13(5):870.PubMedCrossRef
20.
Yang P, Zhang P, Zhang S. RNA-binding protein MEX3A interacting with DVL3 stabilizes Wnt/beta-catenin signaling in endometrial carcinoma. Int J Mol Sci. 2022;24(1):592.PubMedPubMedCentralCrossRef
21.
Watanabe S, Alexander M, Misharin AV, Budinger GRS. The role of macrophages in the resolution of inflammation. J Clin Invest. 2019;129:2619–28.PubMedPubMedCentralCrossRef
22.
23.
Catalana R, Kirkpatrick DR. Verbal approval and anxiety in serial-verbal learning. Psychol Rep. 1968;23:1251–4.PubMedCrossRef
24.
Ascher DP, Shoupe BA, Robb M, Maybee DA, Fischer GW. Comparison of standard and quantitative blood cultures in the evaluation of children with suspected central venous line sepsis. Diagn Microbiol Infect Dis. 1992;15:499–503.PubMedCrossRef
25.
Lv SJ, Sun JN, Gan L, Sun J. Identification of molecular subtypes and immune infiltration in endometriosis: a novel bioinformatics analysis and In vitro validation. Front Immunol. 2023;14:1130738.PubMedPubMedCentralCrossRef
26.
Jiang H, Zhang X, Wu Y, Zhang B, Wei J, Li J, et al. Bioinformatics identification and validation of biomarkers and infiltrating immune cells in endometriosis. Front Immunol. 2022;13: 944683.PubMedPubMedCentralCrossRef
27.
Gan L, Sun J, Sun J. Bioinformatical analysis identifies PDLIM3 as a potential biomarker associated with immune infiltration in patients with endometriosis. PeerJ. 2022;10: e13218.PubMedPubMedCentralCrossRef
28.
Wilson TJ, Hertzog PJ, Angus D, Munnery L, Wood EC, Kola I. Decreased natural killer cell activity in endometriosis patients: relationship to disease pathogenesis. Fertil Steril. 1994;62:1086–8.PubMedCrossRef
29.
Sikora J, Mielczarek-Palacz A, Kondera-Anasz Z. Role of natural killer cell activity in the pathogenesis of endometriosis. Curr Med Chem. 2011;18:200–8.PubMedCrossRef
30.
Kanzaki H, Wang HS, Kariya M, Mori T. Suppression of natural killer cell activity by sera from patients with endometriosis. Am J Obstet Gynecol. 1992;167:257–61.PubMedCrossRef
31.
Riccio LGC, Baracat EC, Chapron C, Batteux F, Abrao MS. The role of the B lymphocytes in endometriosis: a systematic review. J Reprod Immunol. 2017;123:29–34.PubMedCrossRef
32.
Cargnello M. Roux PP (2011) Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev. 2011;75:50–83.PubMedPubMedCentralCrossRef
33.
Zhang Y, Peng C, Wu G, Wang Y, Liu R, Yang S, et al. Expression of NLK and its potential effect in ovarian cancer chemotherapy. Int J Gynecol Cancer. 2011;21:1380–7.PubMedCrossRef
34.
Wang X, Veeraraghavan J, Liu CC, Cao X, Qin L, Kim JA, et al. Therapeutic targeting of nemo-like kinase in primary and acquired endocrine-resistant breast cancer. Clin Cancer Res. 2021;27:2648–62.PubMedPubMedCentralCrossRef
35.
Shi C, Xu L, Tang Z, Zhang W, Wei Y, Ni J, et al. Knockdown of nemo-like kinase promotes metastasis in non-small-cell lung cancer. Oncol Rep. 2019;42:1090–100.PubMedPubMedCentral
36.
Bhowmick R, Lerdrup M, Gadi SA, Rossetti GG, Singh MI, Liu Y, et al. RAD51 protects human cells from transcription-replication conflicts. Mol Cell. 2022;82(3366–3381): e9.
37.
Choi YS, Park JH, Lee JH, Yoon JK, Yun BH, Park JH, et al. Association between impairment of DNA double strand break repair and decreased ovarian reserve in patients with endometriosis. Front Endocrinol (Lausanne). 2018;9:772.PubMedCrossRef
38.
Barrio-Alonso E, Lituma PJ, Notaras MJ, Albero R, Bouchekioua Y, Wayland N, et al. Circadian protein TIMELESS regulates synaptic function and memory by modulating cAMP signaling. Cell Rep. 2023;42: 112375.PubMedPubMedCentralCrossRef
39.
Cao M, Wang Y, Xiao Y, Zheng D, Zhi C, Xia X, et al. Activation of the clock gene TIMELESS by H3k27 acetylation promotes colorectal cancer tumorigenesis by binding to Myosin-9. J Exp Clin Cancer Res. 2021;40:162.PubMedPubMedCentralCrossRef
40.
Zhang S, Huang P, Dai H, Li Q, Hu L, Peng J, et al. TIMELESS regulates sphingolipid metabolism and tumor cell growth through Sp1/ACER2/S1P axis in ER-positive breast cancer. Cell Death Dis. 2020;11:892.PubMedPubMedCentralCrossRef
41.
Wei S, Wu X, Chen M, Xiang Z, Li X, Zhang J, et al. Exosomal-miR-129-2-3p derived from Fusobacterium nucleatum-infected intestinal epithelial cells promotes experimental colitis through regulating TIMELESS-mediated cellular senescence pathway. Gut Microbes. 2023;15:2240035.PubMedPubMedCentralCrossRef
42.
Shen X, Li M, Mao Z, Yu W. Loss of circadian protein TIMELESS accelerates the progression of cellular senescence. Biochem Biophys Res Commun. 2018;503:2784–91.PubMedCrossRef
43.
Xing X, Gu F, Hua L, Cui X, Li D, Wu Z, et al. TIMELESS promotes tumor progression by enhancing macrophages recruitment in ovarian cancer. Front Oncol. 2021;11: 732058.PubMedPubMedCentralCrossRef
44.
Morales-Santana S, Morell S, Leon J, Carazo-Gallego A, Jimenez-Lopez JC, Morell M. An overview of the polymorphisms of circadian genes associated with endocrine cancer. Front Endocrinol (Lausanne). 2019;10:104.PubMedCrossRef
45.
Wang Z, He S, Xin L, Zhou Y, Zhao L, Wang F. HMGB1-mediated transcriptional activation of circadian gene TIMELESS contributes to endometrial cancer progression through Wnt-beta-catenin pathway. Cell Signal. 2024;116: 111045.PubMedCrossRef
46.
Khan SF, Damerell V, Omar R, Du Toit M, Khan M, Maranyane HM, et al. The roles and regulation of TBX3 in development and disease. Gene. 2020;726: 144223.PubMedCrossRef
47.
Liang B, Zhou Y, Qian M, Xu M, Wang J, Zhang Y, et al. TBX3 functions as a tumor suppressor downstream of activated CTNNB1 mutants during hepatocarcinogenesis. J Hepatol. 2021;75:120–31.PubMedPubMedCentralCrossRef
48.
Yotova I, Hsu E, Do C, Gaba A, Sczabolcs M, Dekan S, et al. Epigenetic alterations affecting transcription factors and signaling pathways in stromal cells of endometriosis. PLoS ONE. 2017;12: e0170859.PubMedPubMedCentralCrossRef
49.
Guo R, Luo J, Chang J, Rekhtman N, Arcila M, Drilon A. MET-dependent solid tumours: molecular diagnosis and targeted therapy. Nat Rev Clin Oncol. 2020;17:569–87.PubMedPubMedCentralCrossRef
50.
Khan KN, Masuzaki H, Fujishita A, Kitajima M, Sekine I, Matsuyama T, et al. Estrogen and progesterone receptor expression in macrophages and regulation of hepatocyte growth factor by ovarian steroids in women with endometriosis. Hum Reprod. 2005;20:2004–13.PubMedCrossRef
51.
Yoshida S, Harada T, Mitsunari M, Iwabe T, Sakamoto Y, Tsukihara S, et al. Hepatocyte growth factor/Met system promotes endometrial and endometriotic stromal cell invasion via autocrine and paracrine pathways. J Clin Endocrinol Metab. 2004;89:823–32.PubMedCrossRef
52.
Yamashita Y, Akatsuka S, Shinjo K, Yatabe Y, Kobayashi H, Seko H, et al. Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis. PLoS ONE. 2013;8: e57724.PubMedPubMedCentralCrossRef
53.
Cheng YC, Chiang HY, Cheng SJ, Chang HW, Li YJ, Shieh SY. Loss of the tumor suppressor BTG3 drives a pro-angiogenic tumor microenvironment through HIF-1 activation. Cell Death Dis. 2020;11:1046.PubMedPubMedCentralCrossRef
54.
Ren T, Hou J, Liu C, Shan F, Xiong X, Qin A, et al. The long non-coding RNA HOTAIRM1 suppresses cell progression via sponging endogenous miR-17-5p/ B-cell translocation gene 3 (BTG3) axis in 5-fluorouracil resistant colorectal cancer cells. Biomed Pharmacother. 2019;117: 109171.PubMedCrossRef
55.
Geng R, Huang X, Li L, Guo X, Wang Q, Zheng Y, et al. Gene expression analysis in endometriosis: Immunopathology insights, transcription factors and therapeutic targets. Front Immunol. 2022;13:1037504.PubMedPubMedCentralCrossRef
56.
Bjorkman S, Taylor HS. MicroRNAs in endometriosis: biological function and emerging biomarker candidatesdagger. Biol Reprod. 2019;100:1135–46.PubMedPubMedCentral
Metadaten
Titel
Identification of diagnostic markers related to inflammatory response and cellular senescence in endometriosis using machine learning and in vitro experiment
verfasst von
Pusheng Yang
Yaxin Miao
Tao Wang
Jing Sun
Publikationsdatum
04.05.2024
Verlag
Springer International Publishing
Erschienen in
Inflammation Research
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-024-01886-5

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise