Expression and clinical significance of RUNX1 in gastric cancer based on bioinformatics_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Zhigang , HE Qichen , ZHOU Huinian ,  JIAO Zuoyi

Department of General Surgery, Second Hospital of Lanzhou University, Lanzhou 730030, P. R. China;

Corresponding author：

JIAO Zuoyi, Email: jiaozy@lzu.edu.cn

Keywords：

Runt-related transcription factor 1; gastric cancer; prognosis; extracellular matrixc

DOI：

10.7507/1007-9424.202303040

Video：

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Objective To investigate the expression of Runt-related transcription factor 1 (RUNX1) in gastric cancer and its correlation with clinicopathological features, prognosis and tumor cell invasion ability. Methods ① Database analysis: the expression of RUNX1 in gastric cancer and adjacent tissues were analyzed by TCGA and GEO database. Kaplan-Meier Plotter database was used to analyze the correlation between RUNX1 expression level and overall survival (OS) of gastric cancer patients. GO analysis and KEGG pathway enrichment were used to analyze the possible functions and signaling pathways of RUNX1 in gastric cancer, and gene correlation was verified by GEPIA database. ② Clinical case validation: the cancer tissues and adjacent tissues of 62 patients with gastric cancer admitted to the Second Hospital of Lanzhou University from June 2018 to December 2019 were retrospectively collected for immunohistochemical staining, HE staining and Sirius red staining, and the relation between RUNX1 expression and clinicopathological features and prognosis of patients was explored. ③ Cell experiment: we knocked down RUNX1 by using small interfering RNA, and then analyzed the relation between RUNX1 and the invasion ability of gastric cancer cells by Transwell assay. Results ① Database analysis: RUNX1 was highly expressed in gastric cancer tissues and negatively correlated with OS (P<0.001). GO analysis and KEGG pathway enrichment analysis showed that RUNX1 was not only involved in the construction of collagen in extracellular matrix (ECM), but also significantly enriched in ECM-receptor interaction pathway. The results of GEPIA gene correlation analysis showed that RUNX1 was positively correlated with gene expression involved in ECM-receptor interaction pathway (P<0.05). ② Clinical case validation: the results of immunohistochemical staining showed that RUNX1 was relatively highly expressed in gastric cancer tissues, and the high expression of RUNX1 was a risk factor affecting the postoperative OS of gastric cancer patients (RR=5.074, P=0.034); the expression of RUNX1 in gastric cancer tissues was positively correlated with red staining area of Sirius red staining (r=0.46, P<0.001). ③ Cell experiment: invasion experiments confirmed that the number of invasive AGS or HGC27 cells in si-001 group and si-002 group decreased after RUNX1 knockdown. Conclusion RUNX1 is highly expressed in gastric cancer and suggests a worse survival prognosis, and it is possible that RUNX1 promotes the development of gastric cancer by activating the ECM-receptor interaction pathway.

Citation： LI Zhigang, HE Qichen, ZHOU Huinian, JIAO Zuoyi. Expression and clinical significance of RUNX1 in gastric cancer based on bioinformatics. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(7): 833-841. doi: 10.7507/1007-9424.202303040 Copy

1.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2.	Tan Z. Recent advances in the surgical treatment of advanced gastric cancer: a review. Med Sci Monit, 2019, 25: 3537-3541.
3.	赫捷, 陈万青, 李兆申, 等. 中国胃癌筛查与早诊早治指南 (2022, 北京). 中国肿瘤, 2022, 31(7): 488-527.
4.	Miyoshi H, Shimizu K, Kozu T, et al. t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci U S A, 1991, 88(23): 10431-10434.
5.	Lin TC. RUNX1 and cancer. Biochim Biophys Acta Rev Cancer, 2022, 1877(3): 188715. doi: 10.1016/j.bbcan.2022.188715.
6.	Li Q, Lai Q, He C, et al. RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer. J Exp Clin Cancer Res, 2019, 38(1): 334. doi: 10.1186/s13046-019-1330-9.
7.	Li Q, Lai Q, He C, et al. RUNX1 regulates the proliferation and chemoresistance of colorectal cancer through the Hedgehog signaling pathway. J Cancer, 2021, 12(21): 6363-6371.
8.	Deng YZ, Yao F, Li JJ, et al. RACK1 suppresses gastric tumorigenesis by stabilizing the β-catenin destruction complex. Gastroenterology, 2012, 142(4): 812-823.e15.
9.	于萍, 步宏, 王华, 等. 免疫组化结果的图像分析与人工计数方法的对比研究. 生物医学工程学杂志, 2003, 20(2): 288-290.
10.	刘微. HE染色在临床病理诊断中的应用价值研究. 中国实用医药, 2022, 17(19): 106-108.
11.	Rittié L. Method for picrosirius red-polarization detection of collagen fibers in tissue sections. Methods Mol Biol, 2017, 1627: 395-407.
12.	潘浩磊, 张凯赟, 李楠, 等. EZH2抑制剂EPZ-6438对胃癌细胞侵袭和转移的作用研究. 锦州医科大学学报, 2022, 43(6): 40-45.
13.	Chen ZD, Zhang PF, Xi HQ, et al. Recent advances in the diagnosis, staging, treatment, and prognosis of advanced gastric cancer: a literature review. Front Med (Lausanne), 2021, 8: 744839. doi: 10.3389/fmed.2021.744839.
14.	Feng X, Zheng Z, Wang Y, et al. Elevated RUNX1 is a prognostic biomarker for human head and neck squamous cell carcinoma. Exp Biol Med (Maywood), 2021, 246(5): 538-546.
15.	Liu S, Zhang J, Yin L, et al. The lncRNA RUNX1-IT1 regulates C-FOS transcription by interacting with RUNX1 in the process of pancreatic cancer proliferation, migration and invasion. Cell Death Dis, 2020, 11(6): 412. doi: 10.1038/s41419-020-2617-7.
16.	Whitmore HAB, Amarnani D, O’Hare M, et al. TNF-α signaling regulates RUNX1 function in endothelial cells. FASEB J, 2021, 35(2): e21155. doi: 10.1096/fj.202001668R.
17.	Xie B, Chen X, Zhao L. SNORA71C promotes development and metastasis of breast cancer by regulating RUNX1 and ferroptosis. MedComm (2020), 2023, 4(3): e262. doi: 10.1002/mco2.262.
18.	Bao Y, Wang L, Shi L, et al. Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer. Cell Mol Biol Lett, 2019, 24: 38. doi: 10.1186/s11658-019-0162-0.
19.	Yan P, He Y, Xie K, et al. In silico analyses for potential key genes associated with gastric cancer. PeerJ, 2018, 6: e6092. doi: 10.7717/peerj.6092.
20.	Dubey S, Dubey PK, Umeshappa CS, et al. Inhibition of RUNX1 blocks the differentiation of lung fibroblasts to myofibroblasts. J Cell Physiol, 2022, 237(4): 2169-2182.
21.	Winkler J, Abisoye-Ogunniyan A, Metcalf KJ, et al. Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nat Commun, 2020, 11(1): 5120. doi: 10.1038/s41467-020-18794-x.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Tan Z. Recent advances in the surgical treatment of advanced gastric cancer: a review. Med Sci Monit, 2019, 25: 3537-3541.
3. 赫捷, 陈万青, 李兆申, 等. 中国胃癌筛查与早诊早治指南 (2022, 北京). 中国肿瘤, 2022, 31(7): 488-527.
4. Miyoshi H, Shimizu K, Kozu T, et al. t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci U S A, 1991, 88(23): 10431-10434.
5. Lin TC. RUNX1 and cancer. Biochim Biophys Acta Rev Cancer, 2022, 1877(3): 188715. doi: 10.1016/j.bbcan.2022.188715.
6. Li Q, Lai Q, He C, et al. RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer. J Exp Clin Cancer Res, 2019, 38(1): 334. doi: 10.1186/s13046-019-1330-9.
7. Li Q, Lai Q, He C, et al. RUNX1 regulates the proliferation and chemoresistance of colorectal cancer through the Hedgehog signaling pathway. J Cancer, 2021, 12(21): 6363-6371.
8. Deng YZ, Yao F, Li JJ, et al. RACK1 suppresses gastric tumorigenesis by stabilizing the β-catenin destruction complex. Gastroenterology, 2012, 142(4): 812-823.e15.
9. 于萍, 步宏, 王华, 等. 免疫组化结果的图像分析与人工计数方法的对比研究. 生物医学工程学杂志, 2003, 20(2): 288-290.
10. 刘微. HE染色在临床病理诊断中的应用价值研究. 中国实用医药, 2022, 17(19): 106-108.
11. Rittié L. Method for picrosirius red-polarization detection of collagen fibers in tissue sections. Methods Mol Biol, 2017, 1627: 395-407.
12. 潘浩磊, 张凯赟, 李楠, 等. EZH2抑制剂EPZ-6438对胃癌细胞侵袭和转移的作用研究. 锦州医科大学学报, 2022, 43(6): 40-45.
13. Chen ZD, Zhang PF, Xi HQ, et al. Recent advances in the diagnosis, staging, treatment, and prognosis of advanced gastric cancer: a literature review. Front Med (Lausanne), 2021, 8: 744839. doi: 10.3389/fmed.2021.744839.
14. Feng X, Zheng Z, Wang Y, et al. Elevated RUNX1 is a prognostic biomarker for human head and neck squamous cell carcinoma. Exp Biol Med (Maywood), 2021, 246(5): 538-546.
15. Liu S, Zhang J, Yin L, et al. The lncRNA RUNX1-IT1 regulates C-FOS transcription by interacting with RUNX1 in the process of pancreatic cancer proliferation, migration and invasion. Cell Death Dis, 2020, 11(6): 412. doi: 10.1038/s41419-020-2617-7.
16. Whitmore HAB, Amarnani D, O’Hare M, et al. TNF-α signaling regulates RUNX1 function in endothelial cells. FASEB J, 2021, 35(2): e21155. doi: 10.1096/fj.202001668R.
17. Xie B, Chen X, Zhao L. SNORA71C promotes development and metastasis of breast cancer by regulating RUNX1 and ferroptosis. MedComm (2020), 2023, 4(3): e262. doi: 10.1002/mco2.262.
18. Bao Y, Wang L, Shi L, et al. Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer. Cell Mol Biol Lett, 2019, 24: 38. doi: 10.1186/s11658-019-0162-0.
19. Yan P, He Y, Xie K, et al. In silico analyses for potential key genes associated with gastric cancer. PeerJ, 2018, 6: e6092. doi: 10.7717/peerj.6092.
20. Dubey S, Dubey PK, Umeshappa CS, et al. Inhibition of RUNX1 blocks the differentiation of lung fibroblasts to myofibroblasts. J Cell Physiol, 2022, 237(4): 2169-2182.
21. Winkler J, Abisoye-Ogunniyan A, Metcalf KJ, et al. Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nat Commun, 2020, 11(1): 5120. doi: 10.1038/s41467-020-18794-x.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression and clinical significance of RUNX1 in gastric cancer based on bioinformatics

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