Research Article
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The Role of Glutathione S-Transferases in Pleomorphic Adenomas of the Salivary Glands

Year 2022, Volume 6, Issue 1, 12 - 24, 01.06.2022
https://doi.org/10.47947/ijnls.1072427

Abstract

The aim of this study is to determine the expression levels of GST isoenzymes in salivary gland pleomorphic adenoma from 26 patients. In this study, we investigated the immunohistochemical staining characteristics of the Glutathione-S-transferase alpha (GSTA-1), sigma (GSTS-1), theta (GSTT-1), kappa (GSTK-1), mu (GSTM-1), omega (GSTO-1) isoenzymes in tumor and surrounding tumor-free (normal) salivary gland tissues from 26 patients. For immunohistochemical studies, tissues were obtained from 26 patients with salivary gland pleomorphic adenoma (PA). Tumor and control tissues of patients were compared according to their staining intensity. The correlations between GST expressions in PA tissue were analyzed by Spearman’s rho and the clinicopathological data were examined by Mann Whitney-U test and Spearman’s rho. Considering the differences in the expressions of GST isoenzymes between tumor tissues and normal tissues of the patients; No differences in GSTT1 and GSTS1 isoenzymes expression were found between tumor and normal tissues (p>0.05). GSTM1 and GSTO1 expression were significantly higher in tumor tissues than in normal tissue. However, GSTK1 and GSTA1 expressions were found to be significantly higher in the normal tissues of the patients compared to the tumor tissues. GSTM1 and GSTO1 expressions were increased in salivary gland PAs. These results should be confirmed with a larger series and different enzyme subtypes.

References

  • Alves, F. A., Perez, D. E., Almeida, O. P., Lopes, M. A., & Kowalski, L. P. (2002). Pleomorphic adenoma of the submandibular gland: clinicopathological and immunohistochemical features of 60 cases in Brazil. Archives Otolaryngol Head & Neck Surgery, 128(12), 1400-1403. https://doi.org/ 10.1001/archotol.128.12.1400.
  • Aydın, S., Oguztuzun, S., Gurbuz, N., Gul, A., Sanlı, A., Ozhavzalı, M., Satar, B., Ozan, S., & Karadayı, N. (2010). Immunohistochemical localization of Glutathione S-Transferase Isoenzymes (GSTA, GSTP, GSTM4, and GSTT1) and tumour marker p53 in matched tissue from normal larynx and laryngeal carcinoma: correlations with prognostic factors. Journal of Otolaryngology-Head & Neck Surgery, 39(5). https://doi.org/10.2310/7070.2010.090142
  • Bulus, H., Oğuztüzün, S., Simsek, G., Kilic, M., Ada, A. O., Göl, S., & Iscan M. (2019). Expression of CYP and GST in human normal and colon tumor tissues. Biotechnic & Histochemistry, 94(1), 1-9. https://doi.org/10.1080/10520295.2018.1493220
  • Campbell, J. A. H., Corrigall, A. V., Guy, A., & Kirsch, R. E. (1991). Immunohistologic localization of alpha, mu, and pi class glutathione s-transferases in human tissues. Cancer, 67(6), 1608-1613. https://doi.org/10.1002/1097-0142(19910315)67:6<1608: aid-cncr2820670623>3.0.co;2-s
  • Fatah, L. H., & Khaleel, A. K. (2016). Immunohistochemical Expression of P53 in Benign Pleomorphic Adenomas of Salivary Glands: A clinicopathological study. Medical Journal of Babylon, 13(3), 642-652.
  • Flanagan, J. U., & Jowsey, I. R. (2005). Glutathione transferases. Annual Review of Pharmacology and Toxicology, 45, 51-58.
  • Guzzo, M., Locati, L. D., Prott, F.J., Gatta, G., McGurk, M., & Licitra, L. (2010). Major and minor salivary gland tumors. Critical reviews in Oncology/Hematology, 74(2), 134-148. https://doi.org/10.1016/j.critrevonc.2009.10.004
  • Hayes, J. D., & Pulford, J. D. (1995). The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Critical Reviews in Biochemistry and Molecular Biology, 30(6), 445-520. https://doi.org/ 10.3109/10409239509083491
  • Hayes, P. C., May, L., Hayes, J. D., & Harrison, D. J. (1991). Glutathione S-transferases in human liver cancer. Gut, 32(12), 1546-1549. http://dx.doi.org/10.1136/gut.32.12.1546
  • Horn-Ross, P. L., Ljung, B. M., & Morrow, M. (1997). Environmental factors and the risk of salivary gland cancer. Epidemiology, 414-419. https://doi.org/ 10.1097/00001648-199707000-00011
  • Jordan, R. C., Daniels, T. E., Greenspan, J. S., & Regezi, J. A. (2002). Advanced diagnostic methods in oral and maxillofacial pathology. Part II: immunohistochemical and immunofluorescent methods. Oral Surgery, Oral Meicine, Oral Pathology, Oral Radiology, and Endodontology, 93(1), 56-74. https://doi.org/10.1067/moe.2002.119567
  • Kearns, P. R., Chrzanowska-Lightowlers, Z. M. A., Pieters, R., Veerman, A., & Hall, A. G. (2003). Mu class glutathione S-transferase mRNA isoform expression in acute lymphoblastic leukemia. British Journal of Haematology, 120(1), 80–88. https://doi.org/10.1046/j.1365-2141.2003.04039.x
  • Khandker, M. N. H., Sadat, S. A., Rahman, T., Haider, I. A., & Ahmed, M. (2019). Clinical presentation and histological variation of pleomorphic adenoma of salivary glands. Journal of Bangladesh College of Physicians and Surgeons, 37(2), 72-77. https://doi.org/10.3329/jbcps.v37i2.40563
  • Larasati, Y. A., Yoneda-Kato, N., Nakamae, I., Yokoyama, T., Meiyanto, E., & Kato, J. Y. (2018). Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth. Scientific Reports, 8(1), 1-13. https://doi.org/10.1038/s41598-018-20179-6
  • Li, J., Wang, Q., Yang, Y., Lei, C., Yang, F., Liang, L., & Tang, N. (2019). GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway. Journal of Experimental & Clinical Cancer Research, 38(1), 1-17. https://doi.org/10.1186/s13046-019-1459-6
  • Li, Y., Zhang, Q., Peng, B., Shao, Q., Qian, W., & Zhang, J. Y. (2014). Identification of glutathione S-transferase omega 1 (GSTO1) protein as a novel tumor-associated antigen and its autoantibody in human esophageal squamous cell carcinoma. Tumour Biology, 35 (11), 10871-10877. https://doi.org/10.1007/s13277-014-2394-y
  • Liu, X., Sui, X., Zhang, C., Wei, K., Bao, Y., Xiong, J., Xiong, J., & Tang, F. (2020). Glutathione S-transferase A1 suppresses tumor progression and indicates better prognosis of human primary hepatocellular carcinoma. Journal of Cancer, 11(1), 83. https://doi.org/ 10.7150/jca.36495
  • Lu, Y., Zhou, J., Zhang, J., Wang, Z., Yu, Y., Miao, M., & Yao, Q. (2019). Dual roles of glutathione S-transferase mu 1’in the development and metastasis of hepatocellular carcinoma. Biomedicine & Pharmacotherapy, 120, 109532. https://doi.org/10.1016/j.biopha.2019.109532
  • Meding, S., Balluff, B., Elsner, M., Schone, C., Rauser, S., Nitsche, U., & Walch, A. (2012). Tissue-based proteomics reveals FXYD3, S100A11, and GSTM3 as novel markers for regional lymph node metastasis in colon cancer. The Journal of Pathology, 228(4), 459-470. https://doi.org/10.1002/path.4021
  • Parl, F. F. (2005). Glutathione S-transferase genotypes and cancer risk. Cancer Letters, 221(2), 123-129. https://doi.org/10.1016/j.canlet.2004.06.016
  • Piaggi, S., Marchi, S., Ciancia, E., De Bortoli, N., Lazzarotti, A., Saviozzi, M., & Paolıcchı, A. (2009). Nuclear translocation of glutathione transferase omega is a progression marker in Barrett’s esophagus. Oncology Reports, 21(2), 283-287. https://doi.org/10.3892/or_00000219
  • Polat, K., Doğan, M., Yüce, S., Uysal, I. O., & Müderris, S. (2013). Parotid tail pleomorphic adenoma extending to the parapharyngeal space. The Journal of Craniofacial Surgery, 24(2), e124. https://doi.org/10.1097/SCS.0b013e318266fec7
  • Skálová, A., & Leivo, I. (1996). Cell proliferation in salivary gland tumors. General Diagnostic Pathology, 142(1), 7-16.
  • Stenner, M., & Klussmann, J. P. (2009). Current update on established and novel biomarkers in salivary gland carcinoma pathology and the molecular pathways involved. European Archives of Oto-Rhino-Laryngology, 266(3), 333-341. https://doi.org/ 10.1007/s00405-008-0882-7
  • Stennert, E., Guntinas-Lichius, O., Klussmann, J. P., & Arnold, G. (2001). Histopathology of pleomorphic adenoma in the parotid gland: a prospective unselected series of 100 cases. The Laryngoscope, 11(12), 2195-2200. https://doi.org/10.1097/00005537-200112000-00024
  • Tarakji, B., Kujan, O., & Nassani, M. Z. (2010). Immunohistochemical expression of p53 in pleomorphic adenoma and carcinoma ex pleomorphic adenoma. Journal of Cancer Epidemiology, 250606. https://doi.org/ 10.1155/2010/250606
  • Usarek, E., Kłoniecki, M., Osuch-Wojcikiewicz, ´E., Bruzgielewicz, A., Kukwa, M., Kukwa, A., & Baranczyk-Kuzma, A. (2004). Expression of glutathione-S-transferase isoenzymes in larynx cancer. The Polish Otolaryngology, 58(5), 895-898.
  • Wang, K., Zhang, F. L., & Jia, W. (2021). Glutathione S transferase ω 1 promotes the proliferation, migration, and invasion, and inhibits the apoptosis of non-small cell lung cancer cells, via the JAK/STAT3 signaling pathway. Molecular Medicine Reports, 23 (1), 1-1. https:// doi: 10.3892/mmr.2020.11709
  • Yang, F., Wen, J., Luo, K., & Fu, J. (2021). Low GSTM3 expression is associated with poor disease‐free survival in resected esophageal squamous cell carcinoma. Diagnostic Pathology, 16(1), 1-12. https://doi.org/10.1186/s13000-021-01069-4
  • Zhu, S., Schuerch, C., & Hunt, J. (2015). Review and updates of immunohistochemistry in selected salivary gland and head and neck tumors. Archives of Pathology and Laboratory Medicine, 139(1), 55-66. https://doi.org/10.5858/arpa.2014-0167-RA
  • Zieper, M., Zhang, R., Priddy, R., & Xiao, Y. (1994). The expression of placental glutathione s-transferase (GST-7T) in human normal salivary glands and tumors. International Journal of Oncology 5(4), 961-966. https://doi.org/10.3892/ijo.5.4.961

Year 2022, Volume 6, Issue 1, 12 - 24, 01.06.2022
https://doi.org/10.47947/ijnls.1072427

Abstract

References

  • Alves, F. A., Perez, D. E., Almeida, O. P., Lopes, M. A., & Kowalski, L. P. (2002). Pleomorphic adenoma of the submandibular gland: clinicopathological and immunohistochemical features of 60 cases in Brazil. Archives Otolaryngol Head & Neck Surgery, 128(12), 1400-1403. https://doi.org/ 10.1001/archotol.128.12.1400.
  • Aydın, S., Oguztuzun, S., Gurbuz, N., Gul, A., Sanlı, A., Ozhavzalı, M., Satar, B., Ozan, S., & Karadayı, N. (2010). Immunohistochemical localization of Glutathione S-Transferase Isoenzymes (GSTA, GSTP, GSTM4, and GSTT1) and tumour marker p53 in matched tissue from normal larynx and laryngeal carcinoma: correlations with prognostic factors. Journal of Otolaryngology-Head & Neck Surgery, 39(5). https://doi.org/10.2310/7070.2010.090142
  • Bulus, H., Oğuztüzün, S., Simsek, G., Kilic, M., Ada, A. O., Göl, S., & Iscan M. (2019). Expression of CYP and GST in human normal and colon tumor tissues. Biotechnic & Histochemistry, 94(1), 1-9. https://doi.org/10.1080/10520295.2018.1493220
  • Campbell, J. A. H., Corrigall, A. V., Guy, A., & Kirsch, R. E. (1991). Immunohistologic localization of alpha, mu, and pi class glutathione s-transferases in human tissues. Cancer, 67(6), 1608-1613. https://doi.org/10.1002/1097-0142(19910315)67:6<1608: aid-cncr2820670623>3.0.co;2-s
  • Fatah, L. H., & Khaleel, A. K. (2016). Immunohistochemical Expression of P53 in Benign Pleomorphic Adenomas of Salivary Glands: A clinicopathological study. Medical Journal of Babylon, 13(3), 642-652.
  • Flanagan, J. U., & Jowsey, I. R. (2005). Glutathione transferases. Annual Review of Pharmacology and Toxicology, 45, 51-58.
  • Guzzo, M., Locati, L. D., Prott, F.J., Gatta, G., McGurk, M., & Licitra, L. (2010). Major and minor salivary gland tumors. Critical reviews in Oncology/Hematology, 74(2), 134-148. https://doi.org/10.1016/j.critrevonc.2009.10.004
  • Hayes, J. D., & Pulford, J. D. (1995). The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Critical Reviews in Biochemistry and Molecular Biology, 30(6), 445-520. https://doi.org/ 10.3109/10409239509083491
  • Hayes, P. C., May, L., Hayes, J. D., & Harrison, D. J. (1991). Glutathione S-transferases in human liver cancer. Gut, 32(12), 1546-1549. http://dx.doi.org/10.1136/gut.32.12.1546
  • Horn-Ross, P. L., Ljung, B. M., & Morrow, M. (1997). Environmental factors and the risk of salivary gland cancer. Epidemiology, 414-419. https://doi.org/ 10.1097/00001648-199707000-00011
  • Jordan, R. C., Daniels, T. E., Greenspan, J. S., & Regezi, J. A. (2002). Advanced diagnostic methods in oral and maxillofacial pathology. Part II: immunohistochemical and immunofluorescent methods. Oral Surgery, Oral Meicine, Oral Pathology, Oral Radiology, and Endodontology, 93(1), 56-74. https://doi.org/10.1067/moe.2002.119567
  • Kearns, P. R., Chrzanowska-Lightowlers, Z. M. A., Pieters, R., Veerman, A., & Hall, A. G. (2003). Mu class glutathione S-transferase mRNA isoform expression in acute lymphoblastic leukemia. British Journal of Haematology, 120(1), 80–88. https://doi.org/10.1046/j.1365-2141.2003.04039.x
  • Khandker, M. N. H., Sadat, S. A., Rahman, T., Haider, I. A., & Ahmed, M. (2019). Clinical presentation and histological variation of pleomorphic adenoma of salivary glands. Journal of Bangladesh College of Physicians and Surgeons, 37(2), 72-77. https://doi.org/10.3329/jbcps.v37i2.40563
  • Larasati, Y. A., Yoneda-Kato, N., Nakamae, I., Yokoyama, T., Meiyanto, E., & Kato, J. Y. (2018). Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth. Scientific Reports, 8(1), 1-13. https://doi.org/10.1038/s41598-018-20179-6
  • Li, J., Wang, Q., Yang, Y., Lei, C., Yang, F., Liang, L., & Tang, N. (2019). GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway. Journal of Experimental & Clinical Cancer Research, 38(1), 1-17. https://doi.org/10.1186/s13046-019-1459-6
  • Li, Y., Zhang, Q., Peng, B., Shao, Q., Qian, W., & Zhang, J. Y. (2014). Identification of glutathione S-transferase omega 1 (GSTO1) protein as a novel tumor-associated antigen and its autoantibody in human esophageal squamous cell carcinoma. Tumour Biology, 35 (11), 10871-10877. https://doi.org/10.1007/s13277-014-2394-y
  • Liu, X., Sui, X., Zhang, C., Wei, K., Bao, Y., Xiong, J., Xiong, J., & Tang, F. (2020). Glutathione S-transferase A1 suppresses tumor progression and indicates better prognosis of human primary hepatocellular carcinoma. Journal of Cancer, 11(1), 83. https://doi.org/ 10.7150/jca.36495
  • Lu, Y., Zhou, J., Zhang, J., Wang, Z., Yu, Y., Miao, M., & Yao, Q. (2019). Dual roles of glutathione S-transferase mu 1’in the development and metastasis of hepatocellular carcinoma. Biomedicine & Pharmacotherapy, 120, 109532. https://doi.org/10.1016/j.biopha.2019.109532
  • Meding, S., Balluff, B., Elsner, M., Schone, C., Rauser, S., Nitsche, U., & Walch, A. (2012). Tissue-based proteomics reveals FXYD3, S100A11, and GSTM3 as novel markers for regional lymph node metastasis in colon cancer. The Journal of Pathology, 228(4), 459-470. https://doi.org/10.1002/path.4021
  • Parl, F. F. (2005). Glutathione S-transferase genotypes and cancer risk. Cancer Letters, 221(2), 123-129. https://doi.org/10.1016/j.canlet.2004.06.016
  • Piaggi, S., Marchi, S., Ciancia, E., De Bortoli, N., Lazzarotti, A., Saviozzi, M., & Paolıcchı, A. (2009). Nuclear translocation of glutathione transferase omega is a progression marker in Barrett’s esophagus. Oncology Reports, 21(2), 283-287. https://doi.org/10.3892/or_00000219
  • Polat, K., Doğan, M., Yüce, S., Uysal, I. O., & Müderris, S. (2013). Parotid tail pleomorphic adenoma extending to the parapharyngeal space. The Journal of Craniofacial Surgery, 24(2), e124. https://doi.org/10.1097/SCS.0b013e318266fec7
  • Skálová, A., & Leivo, I. (1996). Cell proliferation in salivary gland tumors. General Diagnostic Pathology, 142(1), 7-16.
  • Stenner, M., & Klussmann, J. P. (2009). Current update on established and novel biomarkers in salivary gland carcinoma pathology and the molecular pathways involved. European Archives of Oto-Rhino-Laryngology, 266(3), 333-341. https://doi.org/ 10.1007/s00405-008-0882-7
  • Stennert, E., Guntinas-Lichius, O., Klussmann, J. P., & Arnold, G. (2001). Histopathology of pleomorphic adenoma in the parotid gland: a prospective unselected series of 100 cases. The Laryngoscope, 11(12), 2195-2200. https://doi.org/10.1097/00005537-200112000-00024
  • Tarakji, B., Kujan, O., & Nassani, M. Z. (2010). Immunohistochemical expression of p53 in pleomorphic adenoma and carcinoma ex pleomorphic adenoma. Journal of Cancer Epidemiology, 250606. https://doi.org/ 10.1155/2010/250606
  • Usarek, E., Kłoniecki, M., Osuch-Wojcikiewicz, ´E., Bruzgielewicz, A., Kukwa, M., Kukwa, A., & Baranczyk-Kuzma, A. (2004). Expression of glutathione-S-transferase isoenzymes in larynx cancer. The Polish Otolaryngology, 58(5), 895-898.
  • Wang, K., Zhang, F. L., & Jia, W. (2021). Glutathione S transferase ω 1 promotes the proliferation, migration, and invasion, and inhibits the apoptosis of non-small cell lung cancer cells, via the JAK/STAT3 signaling pathway. Molecular Medicine Reports, 23 (1), 1-1. https:// doi: 10.3892/mmr.2020.11709
  • Yang, F., Wen, J., Luo, K., & Fu, J. (2021). Low GSTM3 expression is associated with poor disease‐free survival in resected esophageal squamous cell carcinoma. Diagnostic Pathology, 16(1), 1-12. https://doi.org/10.1186/s13000-021-01069-4
  • Zhu, S., Schuerch, C., & Hunt, J. (2015). Review and updates of immunohistochemistry in selected salivary gland and head and neck tumors. Archives of Pathology and Laboratory Medicine, 139(1), 55-66. https://doi.org/10.5858/arpa.2014-0167-RA
  • Zieper, M., Zhang, R., Priddy, R., & Xiao, Y. (1994). The expression of placental glutathione s-transferase (GST-7T) in human normal salivary glands and tumors. International Journal of Oncology 5(4), 961-966. https://doi.org/10.3892/ijo.5.4.961

Details

Primary Language English
Subjects Biochemistry and Molecular Biology
Journal Section Research articles
Authors

Muharrem ATLI> (Primary Author)
Kırıkkale Üniversitesi Fen Bilimleri Enstitüsü 71451 Yahşihan/ Kırıkkale
0000-0002-2453-1370
Türkiye


Sema ÇETİN>
KIRIKKALE ÜNİVERSİTESİ, FEN-EDEBİYAT FAKÜLTESİ, BİYOLOJİ BÖLÜMÜ
0000-0001-8442-4019
Türkiye


Serpil OĞUZTÜZÜN>
KIRIKKALE ÜNİVERSİTESİ, FEN-EDEBİYAT FAKÜLTESİ, BİYOLOJİ BÖLÜMÜ
0000-0002-5892-3735
Türkiye


Kayhan BAŞAK>
SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL KARTAL DR. LÜTFİ KIRDAR ŞEHİR SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ
0000-0003-1960-8924
Türkiye


Sedat AYDIN>
İSTANBUL ÜNİVERSİTESİ, İSTANBUL TIP FAKÜLTESİ, CERRAHİ TIP BİLİMLERİ BÖLÜMÜ, AĞIZ, YÜZ VE ÇENE CERRAHİSİ ANABİLİM DALI
0000-0003-4939-5026
Türkiye


Can YILMAZ>
VAN YÜZÜNCÜ YIL ÜNİVERSİTESİ, FEN FAKÜLTESİ, MOLEKÜLER BİYOLOJİ VE GENETİK BÖLÜMÜ
0000-0002-0028-6614
Türkiye


Gizem KAT ANIL>
SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL KARTAL DR. LÜTFİ KIRDAR ŞEHİR SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ
0000-0003-2031-283X
Türkiye


Mehmet Gökhan DEMİR>
SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL KARTAL DR. LÜTFİ KIRDAR ŞEHİR SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ, CERRAHİ TIP BİLİMLERİ BÖLÜMÜ, KULAK-BURUN-BOĞAZ HASTALIKLARI ANABİLİM DALI
0000-0002-0609-6782
Türkiye


Filiz KARDİYEN>
GAZİ ÜNİVERSİTESİ, FEN FAKÜLTESİ, İSTATİSTİK BÖLÜMÜ
0000-0002-8730-2751
Türkiye


Volkan ATEŞ>
TARSUS UNIVERSITY
0000-0002-2349-0140
Türkiye

Supporting Institution Kırıkkale University Scientific Research and Projects Department
Project Number 2020/035
Thanks The studies were carried out at Kırıkkale University, Department of Biology, Tissue Research Laboratory. I thank all the authors. Also, we thank Dr. Lütfi Kırdar City Hospital Pathology Department. We thank the Kırıkkale University Scientific Research and Projects Department (Project no. 2020/035) for funding this research.
Early Pub Date January 16, 2022
Publication Date June 1, 2022
Application Date February 12, 2022
Acceptance Date May 6, 2022
Published in Issue Year 2022, Volume 6, Issue 1

Cite

APA Atlı, M. , Çetin, S. , Oğuztüzün, S. , Başak, K. , Aydın, S. , Yılmaz, C. , Kat Anıl, G. , Demir, M. G. , Kardiyen, F. & Ateş, V. (2022). The Role of Glutathione S-Transferases in Pleomorphic Adenomas of the Salivary Glands . International Journal of Nature and Life Sciences , 6 (1) , 12-24 . DOI: 10.47947/ijnls.1072427