Prognostic significance of hepatocyte growth factor in non-metastatic colorectal cancer
- Authors: Bogomolova I.A.1, Dolgova D.R.2, Antoneeva I.I.2,3, Abakumova T.V.2, Gening T.P.2, Udalov Y.D.1
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Affiliations:
- Federal Scientific Clinical Centre for Medical Radiology and Oncology, Federal Medical and Biological Agency of Russia
- Ulyanovsk State University
- Regional Clinical Oncology Center
- Issue: Vol 27, No 2 (2024)
- Pages: 383-390
- Section: SHORT COMMUNICATIONS
- URL: https://bakhtiniada.ru/1028-7221/article/view/263703
- DOI: https://doi.org/10.46235/1028-7221-16652-PSO
- ID: 263703
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Abstract
Hepatocyte growth factor (HGF), produced by mesenchymal cells, stimulates mitogenesis and angiogenesis in tumor cells. Tumor cells of some solid tumors do not secrete HGF. The aim of the study was to evaluate the prognostic significance of HGF expression in tumor tissue in colorectal cancer (CRC). The study included 50 patients with stage II-III colorectal cancer; they underwent radical surgical treatment, followed by adjuvant chemotherapy according to the FOLFOX/XELOX regimen. In primary tumor samples, quantitative PCR was used to assess the level of HGF expression. Statistical processing of the obtained data was carried out using STATISTICA 13.0, BioStat v.7.1., and Jamovi 1.6.8 software. The study aims to study a new marker. Comparison of characteristics in the case of non-normal distribution was carried out using the nonparametric Mann–Whitney U test. Cox and Kaplan–Meier linear regression tests were used to analyze progression-free survival. When discussing the results, we used our previously obtained data on the level of expression of TGF-β and CXCL8 in the tumor tissue. As a result of the studies, it was found that in 60% of tumor samples HGF was not expressed, but it was significantly higher than in the resection line samples. Analysis of relapse-free survival in patients with CRC according to the level of HGF expression (predicted level by proportional hazards assessment – 0.7) showed that the median survival in groups 1 (HGF expression more than 0.7) and 2 (HGF expression less than 0.7) was 23.3 and 62.9 months, respectively (long rank test p = 0.215). It was shown that the level of HGF mRNA in CRC tumors does not depend on age, stage of the disease, and sensitivity to FOLFOX/XELOX chemotherapy. The expression level is significantly reduced in tumors with a KRAS mutation and increased in those with a BRAF mutation, in poorly differentiated tumors. Using the level of HGF expression in the tumor tissue of patients with non-metastatic CRC before the start of chemotherapy to assess the prognosis of the relapse-free period is only possible in conjunction with the expression of TGF-β, CXCL8 in the tissue and the level of CEA in the blood of these patients.
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##article.viewOnOriginalSite##About the authors
I. A. Bogomolova
Federal Scientific Clinical Centre for Medical Radiology and Oncology, Federal Medical and Biological Agency of Russia
Email: 73bogomolova@gmail.com
Head, Department of Antitumor Drug Therapy of the Hospital
Russian Federation, DimitrovgradD. R. Dolgova
Ulyanovsk State University
Author for correspondence.
Email: dolgova.dinara@yandex.ru
PhD (Biology), Associate Professor, Department of Physiology and Pathophysiology, Director of the Medical and Biological Research Center
Russian Federation, UlyanovskI. I. Antoneeva
Ulyanovsk State University; Regional Clinical Oncology Center
Email: 73bogomolova@gmail.com
PhD, MD (Medicine), Professor, Department of Oncology and Radiology; Head, Department of Oncogynecology
Russian Federation, Ulyanovsk; UlyanovskT. V. Abakumova
Ulyanovsk State University
Email: 73bogomolova@gmail.com
PhD, MD (Biology), Associate Professor, Professor, Department of Physiology and Pathophysiology
Russian Federation, UlyanovskT. P. Gening
Ulyanovsk State University
Email: 73bogomolova@gmail.com
PhD, MD (Biology), Professor, Head, Department of Physiology and Pathophysiology
Russian Federation, UlyanovskYu. D. Udalov
Federal Scientific Clinical Centre for Medical Radiology and Oncology, Federal Medical and Biological Agency of Russia
Email: 73bogomolova@gmail.com
PhD, MD (Medicine), Associate Professor, External Expert of the FMBA of Russia in Medical Radiology, General Manager
Russian Federation, DimitrovgradReferences
- Богомолова И.А., Долгова Д.Р., Антонеева И.И., Абакумова Т.В., Мягдиева И.Р., Песков А.Б., Генинг Т.П. Предиктивная значимость регуляторов воспаления TGFb1 и CXCL8 в опухолевой ткани при колоректальном раке // Бюллетень сибирской медицины, 2023. Т. 22, № 1. С. 7-13. [Bogomolova I.A., Dolgova D.R., Antoneeva I.I., Abakumova T.V., Myagdieva I.R., Peskov A.B., Gening T.P. Predictive value of inflammatory regulators TGFb1 and CXCL8 in tumor tissue in colorectal cancer. Byulleten sibirskoy meditsiny = Bulletin of Siberian Medicine, 2023, Vol. 22, no. 1, pp. 7-13. (In Russ.)]
- Кит О.И., Геворкян Ю.А., Солдаткина Н.В., Водолажский Д.И. Частота и спектр мутаций гена kras при распространенном колоректальном раке. Клинико-морфологические особенности // Молекулярная медицина, 2015. № 5. С. 26-29. [Kit O.I., Gevorkyan Yu.A., Soldatkina N.V., Vodolazhsky D.I. Frequency and spectrum of kras gene mutations in advanced colorectal cancer. Clinical and morphological characteristics. Molekulyarnaya meditsina = Molecular Medicine, 2015, no. 5, pp. 26-29. (In Russ.)]
- Кит О.И., Геворкян Ю.А., Солдаткина Н.В., Тимошкина Н.Н., Харагезов Д.А., Каймакчи Д.О., Полуэктов С.И., Дашков А.В., Гудцкова Т.Н. Современные прогностические факторы при колоректальном раке // Колопроктология, 2021. Т. 20, № 2. С. 42-49. [Kit O.I., Gevorkyan Yu.A., Soldatkina N.V., Timoshkina N.N., Kharagezov D.A., Kaymakchi D.O., Poluektov S.I., Dashkov A.V., Gudtskova T.N. Prognostic factors in colorectal cancer. Koloproktologiya = Coloproctology, 2021, Vol. 20, no. 2, pp. 42-49. (In Russ.)]
- Birchmeier C., Birchmeier W., Gherardi E., Woude G.F.V. Met, metastasis, motility and more. Nat. Rev. Mol. Cell Biol., 2003, Vol. 4, no. 12, pp. 915-925.
- Bottaro D.P., Rubin J.S., Faletto D.L., Chan A.M., Kmiecik T.E., Woude G.F.V., Aaronson S.A. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science, 1991, Vol. 251, no. 4995, 802-804.
- Jahangiri A., de Lay M., Miller L.M., Carbonell W.S., Hu Y.-L., Lu K., Tom M.W., Paquette J., Tokuyasu T.A., Tsao S., Marshall R., Perry A., Bjorgan K.M., Chaumeil M.M., Ronen S.M., Bergers G., Aghi M.K. Gene expression profile identifies tyrosine kinase c-Met as a targetable mediator of antiangiogenic therapy resistance. Clin. Cancer Res., 2013, Vol. 19, no. 7, pp. 1773-1783.
- Jones G.S., Hoadley K.A., Olsson L.T., Hamilton A.M., Bhattacharya A., Kirk E.L., Tipaldos H.J., Fleming J.M., Love M.I., Nichols H.B., Olshan A.F., Troester M.A. Hepatocyte growth factor pathway expression in breast cancer by race and subtype. Breast Cancer Res., 2021, Vol. 23, no. 1, 80. doi: 10.1186/s13058-021-01460-5.
- Qiu S.Q., van Rooijen J., Nienhuis H.H., van der Vegt B., Timmer-Bosscha H., van Leeuwen-Stok E., Walenkamp A.M.E., van Deurzen C.H.M., de Bock G.H., de Vries E.G.E., Schröder C.P. High hepatocyte growth factor expression in primary tumor predicts better overall survival in male breast cancer. Breast Cancer Res., 2020, Vol. 22, no. 1, 30. doi: 10.1186/s13058-020-01266-x.
- Rapisarda A., Melillo G. Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies. Drug Resist. Updat., 2009, Vol. 12, no. 3, pp. 74-80.
- Seneviratne D., Ma J., Tan X., Kwon Y.-K., Muhammad E., Melhem M., DeFrances M.C., Zarnegar R. Genomic instability causes HGF gene activation in colon cancer cells, promoting their resistance to necroptosis. Gastroenterology, 2015, Vol. 148, no. 1, pp. 181-191.e17.
- Trusolino L., Bertotti A., Comoglio P.M. MET signalling: Principles and functions in development, organ regeneration and cancer. Nat. Rev. Mol. Cell Biol., 2010, Vol. 11, pp. 834-848.
- Viale P.H. The American Cancer Society’s Facts & Figures: 2020 Edition. J. Adv. Pract. Oncol., 2020, Vol. 11, no. 2, pp. 135-136.
- Wang C., Xi W., Ji J., Cai Q., Zhao Q., Jiang J., Zhou C., Shi M., Zhang H., Zhu Z., Zhang J. The prognostic value of HGF-c-MET signaling pathway in Gastric Cancer: a study based on TCGA and GEO databases. Int. J. Med. Sci., 2020, Vol. 17, no. 13, pp. 1946-1955.
- Wang J., Shen J., Huang C., Cao M., Shen L. Clinicopathological significance of BRAFV600E mutation in colorectal cancer: an updated meta-analysis. J. Cancer, 2019, Vol. 10, no. 10, pp. 2332-2341.
- Xu Z., Pang T.C.Y., Liu A.C., Pothula S.P., Mekapogu A.R., Perera C.J., Murakami T., Goldstein D., Pirola R.C., Wilson J.S., Apte M.V. Targeting the HGF/c-MET pathway in advanced pancreatic cancer: a key element of treatment that limits primary tumour growth and eliminates metastasis. Br. J. Cancer, 2020, Vol. 122, no. 10, pp. 1486-1495.
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