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Integrative Network-Based Characterization of Serum Biomarker Interactions in Prostate Cancer Progression

Year 2025, Volume: 5 Issue: 2, 7 - 18, 31.08.2025

Huriye Erbak Yılmaz , Zeynep Özel , Çiğdem Dinçkal , Oğuz Karalar , Zeynep Gülsüm Güç , Mustafa Dinçkal , Mustafa Agah Tekindal , Şerif Şentürk

Abstract

Objective: This study investigates the interactions among key serum biomarkers—Hypoxia-inducible factor-1 alpha (HIF-1α), Thrombospondin-1 (TSP1), Neuropilin-1 (NRP1), and Prostate-specific antigen (PSA)—and clinical parameters including age at diagnosis, diabetes mellitus (DM), hypertension (HT), and smoking status in patients with metastatic prostate cancer (mPCa). The objective was to identify structural and functional interdependencies among these variables using a network-based analytical approach.
Materials and Methods: Network analysis was conducted using JASP software (v0.19.3.0). Variables were modeled as nodes, and partial correlations between them as edges. Edge color represented the direction (positive or negative) of the correlation, while thickness indicated its strength. Network topology was evaluated using graph-theoretical metrics including degree, closeness, betweenness, and eigenvector centrality. Additional measures of density and sparsity were also calculated. Spatial visualization of the network was performed using the Fruchterman–Reingold algorithm.
Results: The network comprised eight variables and 27 connections, yielding a sparsity value of 0.036, indicating a highly dense structure. PSA and TSP1 exhibited the highest betweenness centrality, serving as critical bridging nodes. HT and DM had high degree and closeness centrality values, reflecting central positions within the network. NRP1 displayed the highest clustering coefficient, suggesting a localized regulatory role. A strong negative association was observed between TSP1 and HT.
Conclusion: This study highlights the utility of network analysis as a systems-level tool to explore complex biomarker interactions in mPCa. PSA, TSP1, and NRP1 emerged as key molecular regulators, while systemic conditions such as HT and DM significantly influenced network architecture. These findings warrant further validation through mechanistic and hypothesis-driven statistical studies.

Keywords

Prostate Cancer Serum biomarkers Network analysis Thrombospondin-1 Neuropilin-1 Hypoxia-inducible factor-1 alpha Hypoxia-inducible factor-1 alpha

Ethical Statement

Ethical Approval The study was approved by the Clinical Research Ethics Committee of İzmir Katip Çelebi University Atatürk Training and Research Hospital (Approval No: 0165, dated March 21, 2024).

Project Number

0167

References

  • Mottet N., van den Bergh RCN., Briers E., et al. EAU–EANM–ESTRO–ESUR–SIOG guidelines on prostate cancer 2020 update. Part 1: Screening, diagnosis, and local treatment with curative intent. Eur Urol 2021; 79(2):243–62. Doi: 10.1016/j.eururo.2020.09.042
  • Loeb S., Bjurlin MA., Nicholson J., et al. Overdiagnosis and overtreatment of prostate cancer. Eur Urol 2014; 65(6):1046–55. Doi: 10.1016/j.eururo.2013.12.062
  • Neal DE, Donovan JL, Martin RM, Hamdy FC. Screening for prostate cancer remains controversial. Lancet 2009; 374(9700):1482–3. Doi: 10.1016/S0140-6736(09)61085-0
  • Stefanes N., Cunha-Silva M., de Oliveira Silva L., Walter L., Santos-Silva M., Gartia M. Circulating biomarkers for diagnosis and response to therapies in cancer patients. Int Rev Cell Mol Biol 2025; 391:1-41. Doi: 10.1016/bs.ircmb.2024.08.007
  • Kaur S., Martin-Manso G., Pendrak ML., Garfield SH., Isenberg JS., Roberts DD. Thrombospondin-1 inhibits VEGF receptor-2 signaling by disrupting its association with CD47. J Biol Chem 2010; 285(50):38923–32. Doi: 10.1074/jbc.M110.172304
  • Phelan MW., Forman LW., Perrine SP., Faller DV. Hypoxia increases thrombospondin-1 transcript and protein in cultured endothelial cells. J Lab Clin Med 1998; 132(6):519–29. Doi: 10.1016/S0022-2143(98)90131-7
  • Lawler J., Miao WM., Duquette M., Bouck N., Bronson RT., Hynes RO. Thrombospondin-1 gene expression affects survival and tumor spectrum of p53-deficient mice. Am J Pathol 2001; 159(5):1949–56. Doi: 10.1016/S0002-9440(10)63042-8
  • Vallbo C., Wang W., Damber JE. The expression of thrombospondin-1 in benign prostatic hyperplasia and prostatic intraepithelial neoplasia is decreased in prostate cancer. BJU Int 2004; 93(9):1339–43. Doi:10.1111/j.1464-410x.2004.04818.x
  • Kwak C., Jin RJ., Lee C., Park MS., Lee SE. Thrombospondin-1, vascular endothelial growth factor expression and their relationship with p53 status in prostate cancer and benign prostatic hyperplasia. BJU Int 2002; 89(3):303–9. Doi: 10.1046/j.1464-4096.2001.01417.x
  • Tordjman R., Lepelletier Y., Lemarchandel V., et al. A neuronal receptor, neuropilin-1, is essential for the initiation of the primary immune response. Nat Immunol 2002; 3(5):477–82. Doi:10.1038/ni789
  • Olsson AK., Dimberg A., Kreuger J., Claesson-Welsh L. VEGF receptor signalling – in control of vascular function. Nat Rev Mol Cell Biol 2006; 7(5):359–71. Doi: 10.1038/nrm1911
  • Tse BWC., Volpert M., Ratther E., et al. Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality. Oncogene 2017; 36(24):3417–27. Doi:10.1038/onc.2016.482
  • Zhang P., Chen L., Zhou F., He Z., Wang G., Luo Y. NRP1 promotes prostate cancer progression via modulating EGFR-dependent AKT pathway activation. Cell Death Dis 2023; 14(2):159. Doi:10.1038/s41419-023-05696-1
  • Zhong H., Agani F., Baccala AA., et al. Increased expression of hypoxia-inducible factor-1α in rat and human prostate cancer. Cancer Res 1998; 58(23):5280–4.
  • Liang J., Qian Y., Xu D., Yin Q., Pan HJ. Serum tumor markers, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor, in patients with non-small cell lung cancer before and after intervention. Asian Pac J Cancer Prev 2013; 14(6):3851–4. Doi:10.7314/apjcp.2013.14.6.3851
  • Jia ZZ., Jiang GM., Feng YL. Serum HIF-1α and VEGF levels pre- and post-TACE in patients with primary liver cancer. Chin Med Sci J 2011; 26(3):158–62. Doi:10.1016/S1001-9294(11)60041-2
  • Mitra K., Carvunis AR., Ramesh SK., Ideker T. Integrative approaches for finding modular structure in biological networks. Nat Rev Genet 2013; 14(10):719–32. Doi:10.1038/nrg3552
  • Chicco D., Jurman G. Machine learning can predict survival of patients with heart failure from serum creatinine and ejection fraction alone. BMC Med Inform Decis Mak 2020; 20(1):16. Doi:10.1186/s12911-020-1023-5
  • Barabási AL., Gulbahce N., Loscalzo J. Network medicine: A network-based approach to human disease. Nat Rev Genet 2011; 12(1):56–68. Doi:10.1038/nrg2918
  • Chuang HY., Lee E., Liu YT., Lee D., Ideker T. Network-based classification of breast cancer metastasis. Mol Syst Biol 2007; 3:140. Doi:10.1038/msb4100180
  • Goh KI., Cusick ME., Valle D., Childs B., Vidal M., Barabási AL. The human disease network. Proc Natl Acad Sci U S A 2007;104(21):8685–90. Doi: 10.1073/pnas.0701361104
  • Jeong H., Mason SP., Barabási AL., Oltvai ZN. Lethality and centrality in protein networks. Nature 2001; 411(6833):41–6. Doi: 10.1038/35075138
  • Menche J., Sharma A., Kitsak M., et al. Disease networks: Uncovering disease–disease relationships through the incomplete interactome. Science 2015; 347(6224):1257601. Doi: 10.1126/science.1257601
  • Freeman LC. A set of measures of centrality based on betweenness. Sociometry 1977; 40(1):35–41. Doi: 10.2307/3033543
  • Fruchterman TMJ., Reingold EM. Graph drawing by force-directed placement. Softw Pract Exp 1991; 21(11):1129–64. Doi: 10.1002/spe.4380211102
  • Miyata Y., Sakai H. Thrombospondin-1 in urological cancer: Pathological role, clinical significance, and therapeutic prospects. Int J Mol Sci 2013; 14(6):12249–72. Doi: 10.3390/ijms140612249
  • Lawler J. The functions of thrombospondin-1 and -2. Curr Opin Cell Biol. 2000; 12(5):634–40. Doi: 10.1016/S0955-0674(00)00143-5
  • Kazerounian S., Yee KO., Lawler J. Thrombospondins in cancer. Cell Mol Life Sci 2008; 65(5):700–12. Doi: 10.1007/s00018-007-7486-z
  • Grossfeld GD., Carroll PR., Lindeman N., et al. Thrombospondin-1 expression in patients with pathologic stage T3 prostate cancer undergoing radical prostatectomy: Association with p53 alterations, tumor angiogenesis, and tumor progression. Urology 2002; 59(1):97–102. Doi: 10.1016/s0090-4295(01)01476-5
  • Fitchev PP., Wcislak SM., Lee C., et al. Thrombospondin-1 regulates the normal prostate in vivo through angiogenesis and TGF-β activation. Lab Invest 2010; 90(7):1078–90. Doi: 10.1038/labinvest.2010.90
  • Zhang Y., Zheng D., Zhou T., et al. Androgen deprivation promotes neuroendocrine differentiation and angiogenesis through CREB–EZH2–TSP1 pathway in prostate cancers. Nat Commun 2018; 9(1):4080. Doi: 10.1038/s41467-018-06177-2
  • Buda V., Andor M., Cristescu C., et al. Thrombospondin-1 serum levels in hypertensive patients with endothelial dysfunction after one year of treatment with perindopril. Drug Des Devel Ther 2019; 13:3515–26. Doi: 10.2147/DDDT.S218428
  • Dolmatova E., Waheed N., Olson BM., Patel SA., Mandawat A. The intersection of prostate cancer and hypertension: A call to action. Curr Treat Options Oncol 2023; 24(7):892–905. Doi: 10.1007/s11864-023-01094-z
  • Li J., Li ZP., Xu SS., Wang W. Unraveling the biological link between diabetes mellitus and prostate cancer: Insights and implications. World J Diabetes 2024; 15(6):1367–73. Doi: 10.4239/wjd.v15.i6.1367
  • Bhattacharyya S., Marinic TE., Krukovets I., Hoppe G., Stenina OI. Cell type-specific post-transcriptional regulation of production of the potent antiangiogenic and proatherogenic protein thrombospondin-1 by high glucose. J Biol Chem 2008; 283(9):5699–707. Doi: 10.1074/jbc.M706435200
  • Bhattacharyya S., Sul K., Krukovets I., Nestor C., Li J., Adognravi OS. Novel tissue-specific mechanism of regulation of angiogenesis and cancer growth in response to hyperglycemia. J Am Heart Assoc 2012; 1(6):e005967. Doi: 10.1161/JAHA.112.005967
  • Fu R., Du W., Ding Z., et al. HIF-1α promoted vasculogenic mimicry formation in lung adenocarcinoma through NRP1 upregulation in the hypoxic tumor microenvironment. Cell Death Dis 2021; 12(4):394. Doi: 10.1038/s41419-021-03682-z
  • Dumond A., Pagès G. Neuropilins, as relevant oncology target: Their role in the tumoral microenvironment. Front Cell Dev Biol 2020; 8:662. Doi: 10.3389/fcell.2020.00662

Prostat Kanseri İlerlemesinde Serum Biyobelirteçleri Arasındaki Etkileşimlerin Entegre Ağ Tabanlı Analizi

Year 2025, Volume: 5 Issue: 2, 7 - 18, 31.08.2025

Huriye Erbak Yılmaz , Zeynep Özel , Çiğdem Dinçkal , Oğuz Karalar , Zeynep Gülsüm Güç , Mustafa Dinçkal , Mustafa Agah Tekindal , Şerif Şentürk

Abstract

Amaç: Bu çalışma, metastatik prostat kanseri (mPK) hastalarında Hipoksiye duyarlı faktör-1 alfa (HIF-1α), Trombospondin-1 (TSP1), Nöropilin-1 (NRP1) ve Prostat spesifik antijen (PSA) gibi temel serum biyobelirteçleri ile tanı yaşı, diyabetes mellitus, hipertansiyon ve sigara kullanımı gibi klinik parametreler arasındaki etkileşimleri ağ tabanlı analitik bir yaklaşımla değerlendirmeyi amaçlamaktadır.
Gereç ve Yöntemler: Analiz, JASP yazılımı (v0.19.3.0) ile gerçekleştirilmiştir. Değişkenler düğüm (node), kısmi korelasyonlar ise kenar (edge) olarak modellenmiştir. Kenar renkleri ilişkinin yönünü (pozitif/negatif), kalınlıkları ise ilişkinin gücünü göstermektedir. Ağ yapısı; derece, yakınlık, aradalık ve özvektör merkezilik gibi grafik kuramı temelli ölçütlerle değerlendirilmiş; yoğunluk ve seyreklik değerleri hesaplanmıştır. Düğümlerin konumlandırılmasında Fruchterman–Reingold algoritması kullanılmıştır.
Bulgular: Toplam sekiz değişken ve 27 bağlantıdan oluşan ağın seyreklik değeri 0,036 olarak bulunmuştur; bu da yoğun bir yapı olduğunu göstermektedir. PSA ve TSP1 en yüksek aradalık merkezilik değerleriyle köprü rolü üstlenmiştir. Hipertansiyon ve diyabet, yüksek derece ve yakınlık merkezilik değerleriyle ağın merkezinde yer almıştır. NRP1 en yüksek kümeleme katsayısına sahip olup lokal bir düzenleyici rol üstlenmektedir. TSP1 ile hipertansiyon arasında güçlü negatif bir ilişki gözlenmiştir.
Sonuç: Bu çalışma, metastatik prostat kanserinde biyobelirteçler arası ilişkilerin sistem düzeyinde anlaşılmasında ağ analizinin etkili bir yöntem olduğunu ortaya koymaktadır. PSA, TSP1 ve NRP1 önemli moleküler düzenleyiciler olarak öne çıkarken; hipertansiyon ve diyabetes mellitus gibi sistemik hastalıklar ağ yapısının bütünlüğü üzerinde belirgin rol oynamaktadır. Bulguların mekanistik ve istatistiksel çalışmalarla doğrulanması gerekmektedir.

Keywords

Prostat kanseri Serum biyobelirteçleri Ağ analizi Trombospondin-1 Nöropilin-1 Hipoksiye duyarlı faktör-1 alfa

Ethical Statement

Çalışma, İzmir Katip Çelebi Üniversitesi Atatürk Eğitim ve Araştırma Hastanesi Klinik Araştırmalar Etik Kurulu tarafından onaylanmıştır (Karar No: 0165, Tarih: 21 Mart 2024). Bu çalışmada insan katılımcılarla yürütülen tüm işlemler, kurumsal araştırma kurulunun etik standartlarına ve 1964 Helsinki Bildirgesi ile sonraki değişikliklerine uygun olarak gerçekleştirilmiştir. Çalışmaya dahil edilen tüm katılımcılardan yazılı bilgilendirilmiş onam alınmıştır.

Project Number

0167

References

  • Mottet N., van den Bergh RCN., Briers E., et al. EAU–EANM–ESTRO–ESUR–SIOG guidelines on prostate cancer 2020 update. Part 1: Screening, diagnosis, and local treatment with curative intent. Eur Urol 2021; 79(2):243–62. Doi: 10.1016/j.eururo.2020.09.042
  • Loeb S., Bjurlin MA., Nicholson J., et al. Overdiagnosis and overtreatment of prostate cancer. Eur Urol 2014; 65(6):1046–55. Doi: 10.1016/j.eururo.2013.12.062
  • Neal DE, Donovan JL, Martin RM, Hamdy FC. Screening for prostate cancer remains controversial. Lancet 2009; 374(9700):1482–3. Doi: 10.1016/S0140-6736(09)61085-0
  • Stefanes N., Cunha-Silva M., de Oliveira Silva L., Walter L., Santos-Silva M., Gartia M. Circulating biomarkers for diagnosis and response to therapies in cancer patients. Int Rev Cell Mol Biol 2025; 391:1-41. Doi: 10.1016/bs.ircmb.2024.08.007
  • Kaur S., Martin-Manso G., Pendrak ML., Garfield SH., Isenberg JS., Roberts DD. Thrombospondin-1 inhibits VEGF receptor-2 signaling by disrupting its association with CD47. J Biol Chem 2010; 285(50):38923–32. Doi: 10.1074/jbc.M110.172304
  • Phelan MW., Forman LW., Perrine SP., Faller DV. Hypoxia increases thrombospondin-1 transcript and protein in cultured endothelial cells. J Lab Clin Med 1998; 132(6):519–29. Doi: 10.1016/S0022-2143(98)90131-7
  • Lawler J., Miao WM., Duquette M., Bouck N., Bronson RT., Hynes RO. Thrombospondin-1 gene expression affects survival and tumor spectrum of p53-deficient mice. Am J Pathol 2001; 159(5):1949–56. Doi: 10.1016/S0002-9440(10)63042-8
  • Vallbo C., Wang W., Damber JE. The expression of thrombospondin-1 in benign prostatic hyperplasia and prostatic intraepithelial neoplasia is decreased in prostate cancer. BJU Int 2004; 93(9):1339–43. Doi:10.1111/j.1464-410x.2004.04818.x
  • Kwak C., Jin RJ., Lee C., Park MS., Lee SE. Thrombospondin-1, vascular endothelial growth factor expression and their relationship with p53 status in prostate cancer and benign prostatic hyperplasia. BJU Int 2002; 89(3):303–9. Doi: 10.1046/j.1464-4096.2001.01417.x
  • Tordjman R., Lepelletier Y., Lemarchandel V., et al. A neuronal receptor, neuropilin-1, is essential for the initiation of the primary immune response. Nat Immunol 2002; 3(5):477–82. Doi:10.1038/ni789
  • Olsson AK., Dimberg A., Kreuger J., Claesson-Welsh L. VEGF receptor signalling – in control of vascular function. Nat Rev Mol Cell Biol 2006; 7(5):359–71. Doi: 10.1038/nrm1911
  • Tse BWC., Volpert M., Ratther E., et al. Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality. Oncogene 2017; 36(24):3417–27. Doi:10.1038/onc.2016.482
  • Zhang P., Chen L., Zhou F., He Z., Wang G., Luo Y. NRP1 promotes prostate cancer progression via modulating EGFR-dependent AKT pathway activation. Cell Death Dis 2023; 14(2):159. Doi:10.1038/s41419-023-05696-1
  • Zhong H., Agani F., Baccala AA., et al. Increased expression of hypoxia-inducible factor-1α in rat and human prostate cancer. Cancer Res 1998; 58(23):5280–4.
  • Liang J., Qian Y., Xu D., Yin Q., Pan HJ. Serum tumor markers, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor, in patients with non-small cell lung cancer before and after intervention. Asian Pac J Cancer Prev 2013; 14(6):3851–4. Doi:10.7314/apjcp.2013.14.6.3851
  • Jia ZZ., Jiang GM., Feng YL. Serum HIF-1α and VEGF levels pre- and post-TACE in patients with primary liver cancer. Chin Med Sci J 2011; 26(3):158–62. Doi:10.1016/S1001-9294(11)60041-2
  • Mitra K., Carvunis AR., Ramesh SK., Ideker T. Integrative approaches for finding modular structure in biological networks. Nat Rev Genet 2013; 14(10):719–32. Doi:10.1038/nrg3552
  • Chicco D., Jurman G. Machine learning can predict survival of patients with heart failure from serum creatinine and ejection fraction alone. BMC Med Inform Decis Mak 2020; 20(1):16. Doi:10.1186/s12911-020-1023-5
  • Barabási AL., Gulbahce N., Loscalzo J. Network medicine: A network-based approach to human disease. Nat Rev Genet 2011; 12(1):56–68. Doi:10.1038/nrg2918
  • Chuang HY., Lee E., Liu YT., Lee D., Ideker T. Network-based classification of breast cancer metastasis. Mol Syst Biol 2007; 3:140. Doi:10.1038/msb4100180
  • Goh KI., Cusick ME., Valle D., Childs B., Vidal M., Barabási AL. The human disease network. Proc Natl Acad Sci U S A 2007;104(21):8685–90. Doi: 10.1073/pnas.0701361104
  • Jeong H., Mason SP., Barabási AL., Oltvai ZN. Lethality and centrality in protein networks. Nature 2001; 411(6833):41–6. Doi: 10.1038/35075138
  • Menche J., Sharma A., Kitsak M., et al. Disease networks: Uncovering disease–disease relationships through the incomplete interactome. Science 2015; 347(6224):1257601. Doi: 10.1126/science.1257601
  • Freeman LC. A set of measures of centrality based on betweenness. Sociometry 1977; 40(1):35–41. Doi: 10.2307/3033543
  • Fruchterman TMJ., Reingold EM. Graph drawing by force-directed placement. Softw Pract Exp 1991; 21(11):1129–64. Doi: 10.1002/spe.4380211102
  • Miyata Y., Sakai H. Thrombospondin-1 in urological cancer: Pathological role, clinical significance, and therapeutic prospects. Int J Mol Sci 2013; 14(6):12249–72. Doi: 10.3390/ijms140612249
  • Lawler J. The functions of thrombospondin-1 and -2. Curr Opin Cell Biol. 2000; 12(5):634–40. Doi: 10.1016/S0955-0674(00)00143-5
  • Kazerounian S., Yee KO., Lawler J. Thrombospondins in cancer. Cell Mol Life Sci 2008; 65(5):700–12. Doi: 10.1007/s00018-007-7486-z
  • Grossfeld GD., Carroll PR., Lindeman N., et al. Thrombospondin-1 expression in patients with pathologic stage T3 prostate cancer undergoing radical prostatectomy: Association with p53 alterations, tumor angiogenesis, and tumor progression. Urology 2002; 59(1):97–102. Doi: 10.1016/s0090-4295(01)01476-5
  • Fitchev PP., Wcislak SM., Lee C., et al. Thrombospondin-1 regulates the normal prostate in vivo through angiogenesis and TGF-β activation. Lab Invest 2010; 90(7):1078–90. Doi: 10.1038/labinvest.2010.90
  • Zhang Y., Zheng D., Zhou T., et al. Androgen deprivation promotes neuroendocrine differentiation and angiogenesis through CREB–EZH2–TSP1 pathway in prostate cancers. Nat Commun 2018; 9(1):4080. Doi: 10.1038/s41467-018-06177-2
  • Buda V., Andor M., Cristescu C., et al. Thrombospondin-1 serum levels in hypertensive patients with endothelial dysfunction after one year of treatment with perindopril. Drug Des Devel Ther 2019; 13:3515–26. Doi: 10.2147/DDDT.S218428
  • Dolmatova E., Waheed N., Olson BM., Patel SA., Mandawat A. The intersection of prostate cancer and hypertension: A call to action. Curr Treat Options Oncol 2023; 24(7):892–905. Doi: 10.1007/s11864-023-01094-z
  • Li J., Li ZP., Xu SS., Wang W. Unraveling the biological link between diabetes mellitus and prostate cancer: Insights and implications. World J Diabetes 2024; 15(6):1367–73. Doi: 10.4239/wjd.v15.i6.1367
  • Bhattacharyya S., Marinic TE., Krukovets I., Hoppe G., Stenina OI. Cell type-specific post-transcriptional regulation of production of the potent antiangiogenic and proatherogenic protein thrombospondin-1 by high glucose. J Biol Chem 2008; 283(9):5699–707. Doi: 10.1074/jbc.M706435200
  • Bhattacharyya S., Sul K., Krukovets I., Nestor C., Li J., Adognravi OS. Novel tissue-specific mechanism of regulation of angiogenesis and cancer growth in response to hyperglycemia. J Am Heart Assoc 2012; 1(6):e005967. Doi: 10.1161/JAHA.112.005967
  • Fu R., Du W., Ding Z., et al. HIF-1α promoted vasculogenic mimicry formation in lung adenocarcinoma through NRP1 upregulation in the hypoxic tumor microenvironment. Cell Death Dis 2021; 12(4):394. Doi: 10.1038/s41419-021-03682-z
  • Dumond A., Pagès G. Neuropilins, as relevant oncology target: Their role in the tumoral microenvironment. Front Cell Dev Biol 2020; 8:662. Doi: 10.3389/fcell.2020.00662
There are 38 citations in total.

Details

Primary Language English
Subjects Oncologic Surgery, Urology, Metabolic Medicine, Medical Biochemistry - Proteins, Peptides and Proteomics
Journal Section Research Articles
Authors

Huriye Erbak Yılmaz 0000-0002-8995-5561

Zeynep Özel 0000-0002-1077-1250

Çiğdem Dinçkal

Oğuz Karalar 0000-0002-9190-6064

Zeynep Gülsüm Güç 0000-0001-8960-2208

Mustafa Dinçkal 0000-0003-4905-1602

Mustafa Agah Tekindal 0000-0002-4060-7048

Şerif Şentürk 0000-0003-3963-2294

Project Number 0167
Publication Date August 31, 2025
Submission Date July 8, 2025
Acceptance Date August 28, 2025
Published in Issue Year 2025 Volume: 5 Issue: 2

Cite

APA Erbak Yılmaz, H., Özel, Z., Dinçkal, Ç., … Karalar, O. (2025). Integrative Network-Based Characterization of Serum Biomarker Interactions in Prostate Cancer Progression. Güncel Tıbbi Araştırmaları Dergisi, 5(2), 7-18.
AMA Erbak Yılmaz H, Özel Z, Dinçkal Ç, et al. Integrative Network-Based Characterization of Serum Biomarker Interactions in Prostate Cancer Progression. CJMR. August 2025;5(2):7-18.
Chicago Erbak Yılmaz, Huriye, Zeynep Özel, Çiğdem Dinçkal, Oğuz Karalar, Zeynep Gülsüm Güç, Mustafa Dinçkal, Mustafa Agah Tekindal, and Şerif Şentürk. “Integrative Network-Based Characterization of Serum Biomarker Interactions in Prostate Cancer Progression”. Güncel Tıbbi Araştırmaları Dergisi 5, no. 2 (August 2025): 7-18.
EndNote Erbak Yılmaz H, Özel Z, Dinçkal Ç, Karalar O, Güç ZG, Dinçkal M, Tekindal MA, Şentürk Ş (August 1, 2025) Integrative Network-Based Characterization of Serum Biomarker Interactions in Prostate Cancer Progression. Güncel Tıbbi Araştırmaları Dergisi 5 2 7–18.
IEEE H. Erbak Yılmaz, Z. Özel, Ç. Dinçkal, O. Karalar, Z. G. Güç, M. Dinçkal, M. A. Tekindal, and Ş. Şentürk, “Integrative Network-Based Characterization of Serum Biomarker Interactions in Prostate Cancer Progression”, CJMR, vol. 5, no. 2, pp. 7–18, 2025.
ISNAD Erbak Yılmaz, Huriye et al. “Integrative Network-Based Characterization of Serum Biomarker Interactions in Prostate Cancer Progression”. Güncel Tıbbi Araştırmaları Dergisi 5/2 (August2025), 7-18.
JAMA Erbak Yılmaz H, Özel Z, Dinçkal Ç, Karalar O, Güç ZG, Dinçkal M, Tekindal MA, Şentürk Ş. Integrative Network-Based Characterization of Serum Biomarker Interactions in Prostate Cancer Progression. CJMR. 2025;5:7–18.
MLA Erbak Yılmaz, Huriye et al. “Integrative Network-Based Characterization of Serum Biomarker Interactions in Prostate Cancer Progression”. Güncel Tıbbi Araştırmaları Dergisi, vol. 5, no. 2, 2025, pp. 7-18.
Vancouver Erbak Yılmaz H, Özel Z, Dinçkal Ç, Karalar O, Güç ZG, Dinçkal M, et al. Integrative Network-Based Characterization of Serum Biomarker Interactions in Prostate Cancer Progression. CJMR. 2025;5(2):7-18.
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