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Current Cancer Drug Targets

Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

Comprehensive Analyses and Experiments Confirmed IGFBP5 as a Prognostic Predictor Based on an Aging-genomic Landscape Analysis of Ovarian Cancer

Author(s): Ting-Yu Fan, Li-li Xu, Hong-Feng Zhang, Juan Peng, Dan Liu, Wen-Da Zou, Wen-Jie Feng, Mei Qin, Juan Zhang*, Hui Li* and Yu-Kun Li*

Volume 24, Issue 7, 2024

Published on: 24 November, 2023

Page: [760 - 778] Pages: 19

DOI: 10.2174/0115680096276852231113111412

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Abstract

Background: Ovarian cancer (OC) is one of the malignant diseases of the reproductive system in elderly women. Aging-related genes (ARGs) were involved in tumor malignancy and cellular senescence, but the specifics of these mechanisms in OC remain unknown.

Methods: ARGs expression and survival data of OC patients were collected from TCGA and CPTAC databases. Subtype classification was used to identify the roles of hub ARGs in OC progression, including function enrichment, immune infiltration, and drug sensitivity. LASSO regression was utilized to confirm the prognosis significance for these hub ARGs. MTT, EdU, Transwell, and wounding healing analysis confirmed the effect of IGFBP5 on the proliferation and migration ability of OC cells.

Results: ARGs were ectopically expressed in OC tissues compared to normal ovary tissues. Three molecular subtypes were divided by ARGs for OC patients. There were significant differences in ferroptosis, m6A methylation, prognosis, immune infiltration, angiogenesis, differentiation level, and drug sensitivity among the three groups. LASSO regression indicated that 4 signatures, FOXO4, IGFBP5, OGG1 and TYMS, had important prognosis significance. Moreover, IGFBP5 was significantly correlated with immune infiltration. The hub ARG, IGFBP5, expression was significantly decreased in OC patients compared to normal women. IGFBP5 could also reduce the migration and proliferation ability of OC cells compared to vector and NC groups.

Conclusion: IGFBP5 was correlated with OC prognosis and associated with OC migration and proliferation. This gene may serve as potential prognostic biomarkers and therapeutic targets for OC patients.

Keywords: Ovarian cancer, IGBP5, aging-related genes, immune infiltration, prognostic model, oncogene-induced senescence (OIS).

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Graphical Abstract

Graphical abstract illustrating key findings of the study

[1]
d’Adda di Fagagna, F. Living on a break: Cellular senescence as a DNA-damage response. Nat. Rev. Cancer, 2008, 8(7), 512-522.
[http://dx.doi.org/10.1038/nrc2440] [PMID: 18574463]
[2]
Ewald, J.A.; Desotelle, J.A.; Wilding, G.; Jarrard, D.F. Therapy-induced senescence in cancer. J. Natl. Cancer Inst., 2010, 102(20), 1536-1546.
[http://dx.doi.org/10.1093/jnci/djq364] [PMID: 20858887]
[3]
Blagosklonny, M.V. Hallmarks of cancer and hallmarks of aging. Aging (Albany NY), 2022, 14(9), 4176-4187.
[http://dx.doi.org/10.18632/aging.204082] [PMID: 35533376]
[4]
Ren, J.L.; Pan, J.S.; Lu, Y.P.; Sun, P.; Han, J. Inflammatory signaling and cellular senescence. Cell. Signal., 2009, 21(3), 378-383.
[http://dx.doi.org/10.1016/j.cellsig.2008.10.011] [PMID: 18992324]
[5]
Braig, M.; Lee, S.; Loddenkemper, C.; Rudolph, C.; Peters, A.H.F.M.; Schlegelberger, B.; Stein, H.; Dörken, B.; Jenuwein, T.; Schmitt, C.A. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature, 2005, 436(7051), 660-665.
[http://dx.doi.org/10.1038/nature03841] [PMID: 16079837]
[6]
Manukyan, M.; Singh, P.B. Epigenetic rejuvenation. Genes Cells, 2012, 17(5), 337-343.
[http://dx.doi.org/10.1111/j.1365-2443.2012.01595.x] [PMID: 22487104]
[7]
Pan, B.; Zhao, D.; Liu, Y.; Li, N.; Song, C.; Li, N.; Li, X.; Li, M.; Zhao, Z. Establishment and characterization of breast cancer organoids from a patient with mammary Paget’s disease. Cancer Cell Int., 2020, 20(1), 365.
[http://dx.doi.org/10.1186/s12935-020-01459-6] [PMID: 32774159]
[8]
Parikh, N.; Shuck, R.L.; Gagea, M.; Shen, L.; Donehower, L.A. Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene-induced lung tumors in aged mice. Aging Cell, 2018, 17(1), e12691.
[http://dx.doi.org/10.1111/acel.12691] [PMID: 29047229]
[9]
Sprenger, C.C.T.; Drivdahl, R.H.; Woodke, L.B.; Eyman, D.; Reed, M.J.; Carter, W.G.; Plymate, S.R. Senescence-induced alterations of laminin chain expression modulate tumorigenicity of prostate cancer cells. Neoplasia, 2008, 10(12), 1350-1361.
[http://dx.doi.org/10.1593/neo.08746] [PMID: 19048114]
[10]
Kudryavtseva, A.V.; Krasnov, G.S.; Dmitriev, A.A.; Alekseev, B.Y.; Kardymon, O.L.; Sadritdinova, A.F.; Fedorova, M.S.; Pokrovsky, A.V.; Melnikova, N.V.; Kaprin, A.D.; Moskalev, A.A.; Snezhkina, A.V. Mitochondrial dysfunction and oxidative stress in aging and cancer. Oncotarget, 2016, 7(29), 44879-44905.
[http://dx.doi.org/10.18632/oncotarget.9821] [PMID: 27270647]
[11]
López-Otín, C.; Pietrocola, F.; Roiz-Valle, D.; Galluzzi, L.; Kroemer, G. Meta-hallmarks of aging and cancer. Cell Metab., 2023, 35(1), 12-35.
[http://dx.doi.org/10.1016/j.cmet.2022.11.001] [PMID: 36599298]
[12]
Li, Z.; Low, V.; Luga, V.; Sun, J.; Earlie, E.; Parang, B.; Shobana Ganesh, K.; Cho, S.; Endress, J.; Schild, T.; Hu, M.; Lyden, D.; Jin, W.; Guo, C.; Dephoure, N.; Cantley, L.C.; Laughney, A.M.; Blenis, J. Tumor-produced and aging-associated oncometabolite methylmalonic acid promotes cancer-associated fibroblast activation to drive metastatic progression. Nat. Commun., 2022, 13(1), 6239.
[http://dx.doi.org/10.1038/s41467-022-33862-0] [PMID: 36266345]
[13]
Wang, X.; Ma, L.; Pei, X.; Wang, H.; Tang, X.; Pei, J.F.; Ding, Y.N.; Qu, S.; Wei, Z.Y.; Wang, H.Y.; Wang, X.; Wei, G.H.; Liu, D.P.; Chen, H.Z. Comprehensive assessment of cellular senescence in the tumor microenvironment. Brief. Bioinform., 2022, 23(3), bbac118.
[http://dx.doi.org/10.1093/bib/bbac118] [PMID: 35419596]
[14]
Waters, J.A.; Urbano, I.; Robinson, M.; House, C.D. Insulin-like growth factor binding protein 5: Diverse roles in cancer. Front. Oncol., 2022, 12, 1052457.
[http://dx.doi.org/10.3389/fonc.2022.1052457] [PMID: 36465383]
[15]
Sanada, F.; Taniyama, Y.; Muratsu, J.; Otsu, R.; Shimizu, H.; Rakugi, H.; Morishita, R. IGF Binding Protein-5 Induces Cell Senescence. Front. Endocrinol. (Lausanne), 2018, 9, 53.
[http://dx.doi.org/10.3389/fendo.2018.00053] [PMID: 29515523]
[16]
Nojima, I.; Hosoda, R.; Toda, Y.; Saito, Y.; Ueda, N.; Horimoto, K.; Iwahara, N.; Horio, Y.; Kuno, A. Downregulation of IGFBP5 contributes to replicative senescence via ERK2 activation in mouse embryonic fibroblasts. Aging (Albany NY), 2022, 14(7), 2966-2988.
[http://dx.doi.org/10.18632/aging.203999] [PMID: 35378512]
[17]
Wuestefeld, A.; Iakovleva, V.; Yap, S.X.L.; Ong, A.B.L.; Huang, D.Q.; Shuen, T.W.H.; Toh, H.C.; Dan, Y.Y.; Zender, L.; Wuestefeld, T. A Pro-Regenerative Environment Triggers Premalignant to Malignant Transformation of Senescent Hepatocytes. Cancer Res., 2023, 83(3), 428-440.
[http://dx.doi.org/10.1158/0008-5472.CAN-22-1477] [PMID: 36449018]
[18]
Walker, G.; MacLeod, K.; Williams, A.R.W.; Cameron, D.A.; Smyth, J.F.; Langdon, S.P. Insulin-like growth factor binding proteins IGFBP3, IGFBP4, and IGFBP5 predict endocrine responsiveness in patients with ovarian cancer. Clin. Cancer Res., 2007, 13(5), 1438-1444.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-2245] [PMID: 17332286]
[19]
Tomczak, K.; Czerwińska, P.; Wiznerowicz, M. Review The Cancer Genome Atlas (TCGA): An immeasurable source of knowledge. Contemp. Oncol. (Pozn.), 2015, 1A(1A), 68-77.
[http://dx.doi.org/10.5114/wo.2014.47136] [PMID: 25691825]
[20]
Cerami, E.; Gao, J.; Dogrusoz, U.; Gross, B.E.; Sumer, S.O.; Aksoy, B.A.; Jacobsen, A.; Byrne, C.J.; Heuer, M.L.; Larsson, E.; Antipin, Y.; Reva, B.; Goldberg, A.P.; Sander, C.; Schultz, N. The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov., 2012, 2(5), 401-404.
[http://dx.doi.org/10.1158/2159-8290.CD-12-0095] [PMID: 22588877]
[21]
Dennis, G., Jr; Sherman, B.T.; Hosack, D.A.; Yang, J.; Gao, W.; Lane, H.C.; Lempicki, R.A. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol., 2003, 4(5), P3.
[http://dx.doi.org/10.1186/gb-2003-4-5-p3] [PMID: 12734009]
[22]
Zhang, J.; Li, Y.; Fan, T.; Liu, D.; Zou, W.; Li, H.; Li, Y. Identification of bromodomain-containing proteins prognostic value and expression significance based on a genomic landscape analysis of ovarian serous cystadenocarcinoma. Front. Oncol., 2022, 12, 1021558.
[http://dx.doi.org/10.3389/fonc.2022.1021558] [PMID: 36276071]
[23]
Yue, T.; Chen, S.; Zhu, J.; Guo, S.; Huang, Z.; Wang, P.; Zuo, S.; Liu, Y. The aging-related risk signature in colorectal cancer. Aging (Albany NY), 2021, 13(5), 7330-7349.
[http://dx.doi.org/10.18632/aging.202589] [PMID: 33658390]
[24]
Yu, J.; Shi, L.; Lin, W.; Lu, B.; Zhao, Y. UCP2 promotes proliferation and chemoresistance through regulating the NF-κB/β-catenin axis and mitochondrial ROS in gallbladder cancer. Biochem. Pharmacol., 2020, 172, 113745.
[http://dx.doi.org/10.1016/j.bcp.2019.113745] [PMID: 31811866]
[25]
Cheng, Y.; Xu, T.; Li, S.; Ruan, H. GPX1, a biomarker for the diagnosis and prognosis of kidney cancer, promotes the progression of kidney cancer. Aging (Albany NY), 2019, 11(24), 12165-12176.
[http://dx.doi.org/10.18632/aging.102555] [PMID: 31844035]
[26]
Giatromanolaki, A.; Harris, A.L.; Koukourakis, M.I. The prognostic and therapeutic implications of distinct patterns of argininosuccinate synthase 1 (ASS1) and arginase-2 (ARG2) expression by cancer cells and tumor stroma in non-small-cell lung cancer. Cancer Metab., 2021, 9(1), 28.
[http://dx.doi.org/10.1186/s40170-021-00264-7] [PMID: 34344457]
[27]
Chen, X.; Yu, X.; Shen, E. Overexpression of CDKN2B is involved in poor gastric cancer prognosis. J. Cell. Biochem., 2019, 120(12), 19825-19831.
[http://dx.doi.org/10.1002/jcb.29287] [PMID: 31297846]
[28]
Niu, J.; Huang, Y.J.; Wei, S.; Liu, Z.; Wang, L.E.; Chang, S.; Chamberlain, R.M.; El-Naggar, A.K.; Sturgis, E.M.; Wei, Q. Association between a functional polymorphism (-1195T>C) in the IGFBP5 promoter and head and neck cancer risk. Head Neck, 2011, 33(5), 650-660.
[http://dx.doi.org/10.1002/hed.21514] [PMID: 20949447]
[29]
Garner, C.P.; Ding, Y.C.; John, E.M.; Ingles, S.A.; Olopade, O.I.; Huo, D.; Adebamowo, C.; Ogundiran, T.; Neuhausen, S.L. Genetic variation in IGFBP2 and IGFBP5 is associated with breast cancer in populations of African descent. Hum. Genet., 2008, 123(3), 247-255.
[http://dx.doi.org/10.1007/s00439-008-0468-x] [PMID: 18210156]
[30]
Hu, X.; Yuan, P.; Yan, J.; Feng, F.; Li, X.; Liu, W.; Yang, Y. Gene Polymorphisms of ADIPOQ +45T>G, UCP2 -866G>A, and FABP2 Ala54Thr on the Risk of Colorectal Cancer: A Matched Case-Control Study. PLoS One, 2013, 8(6), e67275.
[http://dx.doi.org/10.1371/journal.pone.0067275] [PMID: 23826253]
[31]
Rojas, V.; Hirshfield, K.; Ganesan, S.; Rodriguez-Rodriguez, L. Molecular Characterization of Epithelial Ovarian Cancer: Implications for Diagnosis and Treatment. Int. J. Mol. Sci., 2016, 17(12), 2113.
[http://dx.doi.org/10.3390/ijms17122113] [PMID: 27983698]
[32]
Shimada, S.; Tanaka, S. Molecular targeted drugs, comprehensive classification and preclinical models for the implementation of precision immune oncology in hepatocellular carcinoma. Int. J. Clin. Oncol., 2022, 27(7), 1101-1109.
[http://dx.doi.org/10.1007/s10147-022-02174-0] [PMID: 35633441]
[33]
Wang, Z.; Liu, X.; Ho, R.; Lam, C.; Chow, M. Precision or Personalized Medicine for Cancer Chemotherapy: Is there a Role for Herbal Medicine. Molecules, 2016, 21(7), 889.
[http://dx.doi.org/10.3390/molecules21070889] [PMID: 27399658]
[34]
Lu, X.; Zhang, L.; Zhao, H.; Chen, C.; Wang, Y.; Liu, S.; Lin, X.; Wang, Y.; Zhang, Q.; Lu, T.; Yan, F. Molecular classification and subtype-specific drug sensitivity research of uterine carcinosarcoma under multi-omics framework. Cancer Biol. Ther., 2019, 20(2), 227-235.
[http://dx.doi.org/10.1080/15384047.2018.1523853] [PMID: 30359167]
[35]
Zhang, C.; Liu, X.; Jin, S.; Chen, Y.; Guo, R. Ferroptosis in cancer therapy: A novel approach to reversing drug resistance. Mol. Cancer, 2022, 21(1), 47.
[http://dx.doi.org/10.1186/s12943-022-01530-y] [PMID: 35151318]
[36]
Wang, Y.; Zheng, L.; Shang, W.; Yang, Z.; Li, T.; Liu, F.; Shao, W.; Lv, L.; Chai, L.; Qu, L.; Xu, Q.; Du, J.; Liang, X.; Zeng, J.; Jia, J. Wnt/beta-catenin signaling confers ferroptosis resistance by targeting GPX4 in gastric cancer. Cell Death Differ., 2022, 29(11), 2190-2202.
[http://dx.doi.org/10.1038/s41418-022-01008-w] [PMID: 35534546]
[37]
Nie, Z.; Chen, M.; Gao, Y.; Huang, D.; Cao, H.; Peng, Y.; Guo, N.; Wang, F.; Zhang, S. Ferroptosis and Tumor Drug Resistance: Current Status and Major Challenges. Front. Pharmacol., 2022, 13, 879317.
[http://dx.doi.org/10.3389/fphar.2022.879317] [PMID: 35668934]
[38]
Li, L.; Qiu, C.; Hou, M.; Wang, X.; Huang, C.; Zou, J.; Liu, T.; Qu, J. Ferroptosis in Ovarian Cancer: A Novel Therapeutic Strategy. Front. Oncol., 2021, 11, 665945.
[http://dx.doi.org/10.3389/fonc.2021.665945] [PMID: 33996593]
[39]
Li, G.; Lin, Y.; Zhang, Y.; Gu, N.; Yang, B.; Shan, S.; Liu, N.; Ouyang, J.; Yang, Y.; Sun, F.; Xu, H. Endometrial stromal cell ferroptosis promotes angiogenesis in endometriosis. Cell Death Discov., 2022, 8(1), 29.
[http://dx.doi.org/10.1038/s41420-022-00821-z] [PMID: 35039492]
[40]
Liu, C.Q.; Liu, X.Y.; Ouyang, P.W.; Liu, Q.; Huang, X.M.; Xiao, F.; Cui, Y.H.; Zhou, Q.; Pan, H.W. Ferrostatin-1 attenuates pathological angiogenesis in oxygen-induced retinopathy via inhibition of ferroptosis. Exp. Eye Res., 2023, 226, 109347.
[http://dx.doi.org/10.1016/j.exer.2022.109347] [PMID: 36502924]
[41]
Gao, W.; Wang, X.; Zhou, Y.; Wang, X.; Yu, Y. Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy. Signal Transduct. Target. Ther., 2022, 7(1), 196.
[http://dx.doi.org/10.1038/s41392-022-01046-3] [PMID: 35725836]
[42]
Lin, R.; Fogarty, C.E.; Ma, B.; Li, H.; Ni, G.; Liu, X.; Yuan, J.; Wang, T. Identification of ferroptosis genes in immune infiltration and prognosis in thyroid papillary carcinoma using network analysis. BMC Genomics, 2021, 22(1), 576.
[http://dx.doi.org/10.1186/s12864-021-07895-6] [PMID: 34315405]
[43]
Weijiao, Y.; Fuchun, L.; Mengjie, C.; Xiaoqing, Q.; Hao, L.; Yuan, L.; Desheng, Y. Immune infiltration and a ferroptosis-associated gene signature for predicting the prognosis of patients with endometrial cancer. Aging (Albany NY), 2021, 13(12), 16713-16732.
[http://dx.doi.org/10.18632/aging.203190] [PMID: 34170849]
[44]
Lan, Q.; Liu, P.Y.; Bell, J.L.; Wang, J.Y.; Hüttelmaier, S.; Zhang, X.D.; Zhang, L.; Liu, T. The Emerging Roles of RNA m6A Methylation and Demethylation as Critical Regulators of Tumorigenesis, Drug Sensitivity, and Resistance. Cancer Res., 2021, 81(13), 3431-3440.
[http://dx.doi.org/10.1158/0008-5472.CAN-20-4107] [PMID: 34228629]
[45]
Liu, Z.; Zou, H.; Dang, Q.; Xu, H.; Liu, L.; Zhang, Y.; Lv, J.; Li, H.; Zhou, Z.; Han, X. Biological and pharmacological roles of m6A modifications in cancer drug resistance. Mol. Cancer, 2022, 21(1), 220.
[http://dx.doi.org/10.1186/s12943-022-01680-z] [PMID: 36517820]
[46]
Lin, Z.; Niu, Y.; Wan, A.; Chen, D.; Liang, H.; Chen, X.; Sun, L.; Zhan, S.; Chen, L.; Cheng, C.; Zhang, X.; Bu, X.; He, W.; Wan, G. RNA m 6 A methylation regulates sorafenib resistance in liver cancer through FOXO 3-mediated autophagy. EMBO J., 2020, 39(12), e103181.
[http://dx.doi.org/10.15252/embj.2019103181] [PMID: 32368828]
[47]
Chen, H.M.; Li, H.; Lin, M.X.; Fan, W.J.; Zhang, Y.; Lin, Y.T.; Wu, S.X. Research Progress for RNA Modifications in Physiological and Pathological Angiogenesis. Front. Genet., 2022, 13, 952667.
[http://dx.doi.org/10.3389/fgene.2022.952667] [PMID: 35937999]
[48]
Zhao, Y.; Hu, J.; Sun, X.; Yang, K.; Yang, L.; Kong, L.; Zhang, B.; Li, F.; Li, C.; Shi, B.; Hu, K.; Sun, A.; Ge, J. Loss of m6A demethylase ALKBH5 promotes post-ischemic angiogenesis via post-transcriptional stabilization of WNT5A. Clin. Transl. Med., 2021, 11(5), e402.
[http://dx.doi.org/10.1002/ctm2.402] [PMID: 34047466]
[49]
Yang, Z.; Wang, T.; Wu, D.; Min, Z.; Tan, J.; Yu, B. RNA N6-methyladenosine reader IGF2BP3 regulates cell cycle and angiogenesis in colon cancer. J. Exp. Clin. Cancer Res., 2020, 39(1), 203.
[http://dx.doi.org/10.1186/s13046-020-01714-8] [PMID: 32993738]
[50]
Li, M.; Zha, X.; Wang, S. The role of N6-methyladenosine mRNA in the tumor microenvironment. Biochim. Biophys. Acta Rev. Cancer, 2021, 1875(2), 188522.
[http://dx.doi.org/10.1016/j.bbcan.2021.188522] [PMID: 33545295]
[51]
Liu, X.S.; Zhou, L.M.; Yuan, L.L.; Gao, Y.; Kui, X.Y.; Liu, X.Y.; Pei, Z.J. NPM1 Is a Prognostic Biomarker Involved in Immune Infiltration of Lung Adenocarcinoma and Associated With m6A Modification and Glycolysis. Front. Immunol., 2021, 12, 724741.
[http://dx.doi.org/10.3389/fimmu.2021.724741] [PMID: 34335635]
[52]
Sun, D.; Yang, H.; Fan, L.; Shen, F.; Wang, Z. m6A regulator-mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma. J. Cell. Mol. Med., 2021, 25(21), 10236-10247.
[http://dx.doi.org/10.1111/jcmm.16961] [PMID: 34647423]
[53]
Li, X.; Cao, X.; Li, X.; Zhang, W.; Feng, Y. Expression level of insulin-like growth factor binding protein 5 mRNA is a prognostic factor for breast cancer. Cancer Sci., 2007, 98(10), 1592-1596.
[http://dx.doi.org/10.1111/j.1349-7006.2007.00565.x] [PMID: 17651454]
[54]
Zeng, Z.; Zuo, Y.; Jin, Y.; Peng, Y.; Zhu, X. Identification of Extracellular Matrix Signatures as Novel Potential Prognostic Biomarkers in Lung Adenocarcinoma. Front. Genet., 2022, 13, 872380.
[http://dx.doi.org/10.3389/fgene.2022.872380] [PMID: 35711936]
[55]
Zhong, Z.; Xu, X.; Han, S.; Shao, Y.; Yi, Y. Comprehensive Analysis of Prognostic Value and Immune Infiltration of IGFBP Family Members in Glioblastoma. J. Healthc. Eng., 2022, 2022, 1-13.
[http://dx.doi.org/10.1155/2022/2929695] [PMID: 35832140]
[56]
Li, J.; Jiang, Z.; Han, F.; Liu, S.; Yuan, X.; Tong, J. FOXO4 and FOXD3 are predictive of prognosis in gastric carcinoma patients. Oncotarget, 2016, 7(18), 25585-25592.
[http://dx.doi.org/10.18632/oncotarget.8339] [PMID: 27027443]
[57]
Hwang, H.W.; Ha, S.Y.; Bang, H.; Park, C.K. ATAD2 as a Poor Prognostic Marker for Hepatocellular Carcinoma after Curative Resection. Cancer Res. Treat., 2015, 47(4), 853-861.
[http://dx.doi.org/10.4143/crt.2014.177] [PMID: 25687855]
[58]
Yasuoka, H.; Yamaguchi, Y.; Feghali-Bostwick, C.A. The pro-fibrotic factor IGFBP-5 induces lung fibroblast and mononuclear cell migration. Am. J. Respir. Cell Mol. Biol., 2009, 41(2), 179-188.
[http://dx.doi.org/10.1165/rcmb.2008-0211OC] [PMID: 19131643]
[59]
Ireland, L.; Santos, A.; Campbell, F.; Figueiredo, C.; Hammond, D.; Ellies, L.G.; Weyer-Czernilofsky, U.; Bogenrieder, T.; Schmid, M.; Mielgo, A. Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer. Oncogene, 2018, 37(15), 2022-2036.
[http://dx.doi.org/10.1038/s41388-017-0115-x] [PMID: 29367764]
[60]
Somri-Gannam, L.; Meisel-Sharon, S.; Hantisteanu, S.; Groisman, G.; Limonad, O.; Hallak, M.; Bruchim, I. IGF1R Axis Inhibition Restores Dendritic Cell Antitumor Response in Ovarian Cancer. Transl. Oncol., 2020, 13(8), 100790.
[http://dx.doi.org/10.1016/j.tranon.2020.100790] [PMID: 32428851]
[61]
Sprinzl, M.F.; Puschnik, A.; Schlitter, A.M.; Schad, A.; Ackermann, K.; Esposito, I.; Lang, H.; Galle, P.R.; Weinmann, A.; Heikenwälder, M.; Protzer, U. Sorafenib inhibits macrophage-induced growth of hepatoma cells by interference with insulin-like growth factor-1 secretion. J. Hepatol., 2015, 62(4), 863-870.
[http://dx.doi.org/10.1016/j.jhep.2014.11.011] [PMID: 25463538]
[62]
Beattie, J.; Allan, G.J.; Lochrie, J.D.; Flint, D.J. Insulin-like growth factor-binding protein-5 (IGFBP-5): A critical member of the IGF axis. Biochem. J., 2006, 395(1), 1-19.
[http://dx.doi.org/10.1042/BJ20060086] [PMID: 16526944]
[63]
Dittmer, J. Biological effects and regulation of IGFBP5 in breast cancer. Front. Endocrinol. (Lausanne), 2022, 13, 983793.
[http://dx.doi.org/10.3389/fendo.2022.983793] [PMID: 36093095]
[64]
Deng, Y.; Yang, X.; Hua, H.; Zhang, C. IGFBP5 is Upregulated and Associated with Poor Prognosis in Colorectal Cancer. Int. J. Gen. Med., 2022, 15, 6485-6497.
[http://dx.doi.org/10.2147/IJGM.S370576] [PMID: 35966504]
[65]
Zhang, L.; Li, W.; Cao, L.; Xu, J.; Qian, Y.; Chen, H.; Zhang, Y.; Kang, W.; Gou, H.; Wong, C.C.; Yu, J. PKNOX2 suppresses gastric cancer through the transcriptional activation of IGFBP5 and p53. Oncogene, 2019, 38(23), 4590-4604.
[http://dx.doi.org/10.1038/s41388-019-0743-4] [PMID: 30745575]
[66]
Wang, J.; Ding, N.; Li, Y.; Cheng, H.; Wang, D.; Yang, Q.; Deng, Y.; Yang, Y.; Li, Y.; Ruan, X.; Xie, F.; Zhao, H.; Fang, X. Insulin-like growth factor binding protein 5 (IGFBP5) functions as a tumor suppressor in human melanoma cells. Oncotarget, 2015, 6(24), 20636-20649.
[http://dx.doi.org/10.18632/oncotarget.4114] [PMID: 26010068]
[67]
Sureshbabu, A.; Okajima, H.; Yamanaka, D.; Tonner, E.; Shastri, S.; Maycock, J.; Szymanowska, M.; Shand, J.; Takahashi, S.I.; Beattie, J.; Allan, G.J.; Flint, D.J. IGFBP-5 induces cell adhesion, increases cell survival and inhibits cell migration in MCF-7 human breast cancer cells. J. Cell Sci., 2012, 125(Pt 7), jcs.092882.
[http://dx.doi.org/10.1242/jcs.092882] [PMID: 22328518]
[68]
Dong, C.; Zhang, J.; Fang, S.; Liu, F. IGFBP5 increases cell invasion and inhibits cell proliferation by EMT and Akt signaling pathway in Glioblastoma multiforme cells. Cell Div., 2020, 15(1), 4.
[http://dx.doi.org/10.1186/s13008-020-00061-6] [PMID: 32127912]
[69]
Chan, D.; Zhou, Y.; Chui, C.; Lam, K.; Law, S.; Chan, A.; Li, X.; Lam, A.; Tang, J. Expression of Insulin-Like Growth Factor Binding Protein-5 (IGFBP5) Reverses Cisplatin-Resistance in Esophageal Carcinoma. Cells, 2018, 7(10), 143.
[http://dx.doi.org/10.3390/cells7100143] [PMID: 30241323]
[70]
Luther, G.A.; Lamplot, J.; Chen, X.; Rames, R.; Wagner, E.R.; Liu, X.; Parekh, A.; Huang, E.; Kim, S.H.; Shen, J.; Haydon, R.C.; He, T.C.; Luu, H.H. IGFBP5 domains exert distinct inhibitory effects on the tumorigenicity and metastasis of human osteosarcoma. Cancer Lett., 2013, 336(1), 222-230.
[http://dx.doi.org/10.1016/j.canlet.2013.05.002] [PMID: 23665505]
[71]
Rho, S.B.; Dong, S.M.; Kang, S.; Seo, S.S.; Yoo, C.W.; Lee, D.O.; Woo, J.S.; Park, S.Y. Insulin-like growth factor-binding protein-5 (IGFBP-5) acts as a tumor suppressor by inhibiting angiogenesis. Carcinogenesis, 2008, 29(11), 2106-2111.
[http://dx.doi.org/10.1093/carcin/bgn206] [PMID: 18775916]
[72]
Hwang, J.R.; Cho, Y.J.; Lee, Y.; Park, Y.; Han, H.D.; Ahn, H.J.; Lee, J.H.; Lee, J.W. The C-terminus of IGFBP-5 suppresses tumor growth by inhibiting angiogenesis. Sci. Rep., 2016, 6(1), 39334.
[http://dx.doi.org/10.1038/srep39334] [PMID: 28008951]
[73]
Chen, X.; Yu, Q.; Pan, H.; Li, P.; Wang, X.; Fu, S. Overexpression of IGFBP5 Enhances Radiosensitivity Through PI3K-AKT Pathway in Prostate Cancer. Cancer Manag. Res., 2020, 12, 5409-5418.
[http://dx.doi.org/10.2147/CMAR.S257701] [PMID: 32753958]
[74]
Liu, B.Y.; Soloviev, I.; Huang, X.; Chang, P.; Ernst, J.A.; Polakis, P.; Sakanaka, C. Mammary tumor regression elicited by Wnt signaling inhibitor requires IGFBP5. Cancer Res., 2012, 72(6), 1568-1578.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-3668] [PMID: 22307840]
[75]
Remsing Rix, L.L.; Sumi, N.J.; Hu, Q.; Desai, B.; Bryant, A.T.; Li, X.; Welsh, E.A.; Fang, B.; Kinose, F.; Kuenzi, B.M.; Chen, Y.A.; Antonia, S.J.; Lovly, C.M.; Koomen, J.M.; Haura, E.B.; Marusyk, A.; Rix, U. IGF-binding proteins secreted by cancer-associated fibroblasts induce context-dependent drug sensitization of lung cancer cells. Sci. Signal., 2022, 15(747), eabj5879.
[http://dx.doi.org/10.1126/scisignal.abj5879] [PMID: 35973030]

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