Expression and clinical significance of cold-induced RNA-binding protein in lung adenocarcinoma analyzed based on bioinformatics_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

XIAO Cui , YANG Jianbao ,  WANG Cheng , SUN Yiming , LI Xuan , LI Zheng , LIU Yanbin , AN Haiming

Department of Thoracic Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou, 730030, P. R. China;

Corresponding author：

WANG Cheng, Email: wangchengxw123@sina.com

Keywords：

Cold-induced RNA-binding protein (CIRBP); lung adenocarcinoma; bioinformatics analysis; prognosis

DOI：

10.7507/1007-4848.202102065

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To analyze the expression of cold-induced RNA-binding protein (CIRBP) in lung adenocarcinoma and its clinical significance based on bioinformatics, in order to provide a new direction for the study of therapeutic targets for lung adenocarcinoma.Methods The CIRBP gene expression data and patient clinical information data in lung adenocarcinoma tissues and adjacent tissues were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. The expression of CIRBP in lung adenocarcinoma was analyzed. Furthermore, its relationship with clinicopathological features and prognosis in patients with lung adenocarcinoma was analyzed. GO and KEGG enrichment analysis were carried out for the screened genes. The CIRBP protein interaction network was constructed by STRING, and the correlation analysis was carried out using the GEPIA online website.Results The expression level of CIRBP gene in lung adenocarcinoma tissues was significantly lower than that in adjacent tissues (P<0.01), and its expression level was correlated with T stage and N stage in clinicopathological features. The prognosis of patients with high CIRBP expression in lung adenocarcinoma was significantly better than that with low CIRBP expression. Univariate and multivariate Cox regression analysis showed that CIRBP was an independent prognostic factor in patients with lung adenocarcinoma. GO functional annotation showed its enrichment in organelle fission, nuclear fission, chromosome separation, and DNA replication, etc. KEGG analysis showed that it was mainly involved in cell cycle and DNA replication. Protein interaction network and GEPIA online analysis showed that the expression level of CIRBP was negatively correlated with the expression level of cyclin B2.Conclusion CIRBP gene is down-regulated in lung adenocarcinoma tissues, and its expression level is closely related to patient prognosis. CIRBP gene may be a potential therapeutic target and prognostic marker for lung adenocarcinoma.

Citation： XIAO Cui, YANG Jianbao, WANG Cheng, SUN Yiming, LI Xuan, LI Zheng, LIU Yanbin, AN Haiming. Expression and clinical significance of cold-induced RNA-binding protein in lung adenocarcinoma analyzed based on bioinformatics. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2022, 29(7): 914-922. doi: 10.7507/1007-4848.202102065 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Chien CM, Yang JC, Wu PH, et al. Phytochemical naphtho[1,2-b] furan-4,5-dione induced topoisomerase Ⅱ-mediated DNA damage response in human non-small-cell lung cancer. Phytomedicine, 2019, 54: 109-119.
3.	Hirsch FR, Scagliotti GV, Mulshine JL, et al. Lung cancer: Current therapies and new targeted treatments. Lancet, 2017, 389(10066): 299-311.
4.	Tsiambas E, Lefas AY, Georgiannos SN, et al. EGFR gene deregulation mechanisms in lung adenocarcinoma: A molecular review. Pathol Res Pract, 2016, 212(8): 672-677.
5.	Fahrmann JF, Grapov D, Phinney BS, et al. Proteomic profiling of lung adenocarcinoma indicates heightened DNA repair, antioxidant mechanisms and identifies LASP1 as a potential negative predictor of survival. Clin Proteomics, 2016, 13: 31.
6.	Yamaoka T, Ohmori T, Ohba M, et al. Acquired resistance mechanisms to combination Met-TKI/EGFR-TKI exposure in met-amplified EGFR-TKI-resistant lung adenocarcinoma harboring an activating EGFR mutation. Mol Cancer Ther, 2016, 15(12): 3040-3054.
7.	Choi EB, Yang AY, Kim SC, et al. PARP1 enhances lung adenocarcinoma metastasis by novel mechanisms independent of DNA repair. Oncogene, 2016, 35(35): 4569-4579.
8.	Yang D, Cheng D, Tu Q, et al. HUWE1 controls the development of non-small cell lung cancer through down-regulation of p53. Theranostics, 2018, 8(13): 3517-3529.
9.	Nishiyama H, Higashitsuji H, Yokoi H, et al. Cloning and characterization of human CIRP (cold-inducible RNA-binding protein) cDNA and chromosomal assignment of the gene. Gene, 1997, 204(1-2): 115-120.
10.	Nishiyama H, Itoh K, Kaneko Y, et al. A glycine-rich RNA-binding protein mediating cold-inducible suppression of mammalian cell growth. J Cell Biol, 1997, 137(4): 899-908.
11.	Xue JH, Nonoguchi K, Fukumoto M, et al. Effects of ischemia and H₂O₂ on the cold stress protein CIRP expression in rat neuronal cells. Free Radic Biol Med, 1999, 27(11-12): 1238-1244.
12.	Xia ZP, Zheng XM, Zheng H, et al. Downregulation of cold-inducible RNA-binding protein activates mitogen-activated protein kinases and impairs spermatogenic function in mouse testes. Asian J Androl, 2012, 14(6): 884-889.
13.	Sakurai T, Yada N, Watanabe T, et al. Cold-inducible RNA-binding protein promotes the development of liver cancer. Cancer Sci, 2015, 106(4): 352-358.
14.	Lu M, Ge Q, Wang G, et al. CIRBP is a novel oncogene in human bladder cancer inducing expression of HIF-1α. Cell Death Dis, 2018, 9(10): 1046.
15.	Guo X, Wu Y, Hartley RS. Cold-inducible RNA-binding protein contributes to human antigen R and cyclin E1 deregulation in breast cancer. Mol Carcinog, 2010, 49(2): 130-140.
16.	Hamid AA, Mandai M, Fujita J, et al. Expression of cold-inducible RNA-binding protein in the normal endometrium, endometrial hyperplasia, and endometrial carcinoma. Int J Gynecol Pathol, 2003, 22(3): 240-247.
17.	杨柳, 熊吟, 余永红, 等. 上调 CIRBP 基因表达抑制肾癌细胞的增殖和迁移及其可能的分子机制. 肿瘤, 2020, 40(4): 257-265.
18.	Lujan DA, Ochoa JL, Hartley RS. Cold-inducible RNA binding protein in cancer and inflammation. Wiley Interdiscip Rev RNA, 2018, 9(2).
19.	Brochu C, Cabrita MA, Melanson BD, et al. NF-κB-dependent role for cold-inducible RNA binding protein in regulating interleukin 1β. PLoS One, 2013, 8(2): e57426.
20.	Chen L, Ran D, Xie W, et al. Cold-inducible RNA-binding protein mediates cold air inducible airway mucin production through TLR4/NF-κB signaling pathway. Int Immunopharmacol, 2016, 39: 48-56.
21.	Idrovo JP, Jacob A, Yang WL, et al. A deficiency in cold-inducible RNA-binding protein accelerates the inflammation phase and improves wound healing. Int J Mol Med, 2016, 37(2): 423-428.
22.	Gao S, Ma JJ, Lu C. Prognostic value of cyclin E expression in breast cancer: A meta-analysis. Tumour Biol, 2013, 34(6): 3423-3430.
23.	Indacochea A, Guerrero S, Ureña M, et al. Cold-inducible RNA binding protein promotes breast cancer cell malignancy by regulating Cystatin C levels. RNA, 2021, 27(2): 190-201.
24.	Dankner M, Caron M, Al-Saadi T, et al. Invasive growth associated with cold-inducible RNA-binding protein expression drives recurrence of surgically resected brain metastases. Neuro Oncol, 2021: noab002.
25.	Xu C, Ke D, Zou L, et al. Cold-induced RNA-binding protein (CIRBP) regulates the expression of Src-associated during mitosis of 68 kDa (Sam68) and extracellular signal-regulated kinases (ERK) during heat stress-induced testicular injury. Reprod Fertil Dev, 2020, 32(18): 1357-1364.
26.	Masuda T, Itoh K, Higashitsuji H, et al. Cold-inducible RNA-binding protein (Cirp) interacts with Dyrk1b/Mirk and promotes proliferation of immature male germ cells in mice. Proc Natl Acad Sci U S A, 2012, 109(27): 10885-10890.
27.	Zhang Q, Wang YZ, Zhang W, et al. Involvement of cold inducible rna-binding protein in severe hypoxia-induced growth arrest of neural stem cells in vitro. Mol Neurobiol, 2017, 54(3): 2143-2153.
28.	Qian X, Song X, He Y, et al. CCNB2 overexpression is a poor prognostic biomarker in Chinese NSCLC patients. Biomed Pharmacother, 2015, 74: 222-227.
29.	Wang X, Xiao H, Wu D, et al. miR-335-5p regulates cell cycle and metastasis in lung adenocarcinoma by targeting CCNB2. Onco Targets Ther, 2020, 13: 6255-6263.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Chien CM, Yang JC, Wu PH, et al. Phytochemical naphtho[1,2-b] furan-4,5-dione induced topoisomerase Ⅱ-mediated DNA damage response in human non-small-cell lung cancer. Phytomedicine, 2019, 54: 109-119.
3. Hirsch FR, Scagliotti GV, Mulshine JL, et al. Lung cancer: Current therapies and new targeted treatments. Lancet, 2017, 389(10066): 299-311.
4. Tsiambas E, Lefas AY, Georgiannos SN, et al. EGFR gene deregulation mechanisms in lung adenocarcinoma: A molecular review. Pathol Res Pract, 2016, 212(8): 672-677.
5. Fahrmann JF, Grapov D, Phinney BS, et al. Proteomic profiling of lung adenocarcinoma indicates heightened DNA repair, antioxidant mechanisms and identifies LASP1 as a potential negative predictor of survival. Clin Proteomics, 2016, 13: 31.
6. Yamaoka T, Ohmori T, Ohba M, et al. Acquired resistance mechanisms to combination Met-TKI/EGFR-TKI exposure in met-amplified EGFR-TKI-resistant lung adenocarcinoma harboring an activating EGFR mutation. Mol Cancer Ther, 2016, 15(12): 3040-3054.
7. Choi EB, Yang AY, Kim SC, et al. PARP1 enhances lung adenocarcinoma metastasis by novel mechanisms independent of DNA repair. Oncogene, 2016, 35(35): 4569-4579.
8. Yang D, Cheng D, Tu Q, et al. HUWE1 controls the development of non-small cell lung cancer through down-regulation of p53. Theranostics, 2018, 8(13): 3517-3529.
9. Nishiyama H, Higashitsuji H, Yokoi H, et al. Cloning and characterization of human CIRP (cold-inducible RNA-binding protein) cDNA and chromosomal assignment of the gene. Gene, 1997, 204(1-2): 115-120.
10. Nishiyama H, Itoh K, Kaneko Y, et al. A glycine-rich RNA-binding protein mediating cold-inducible suppression of mammalian cell growth. J Cell Biol, 1997, 137(4): 899-908.
11. Xue JH, Nonoguchi K, Fukumoto M, et al. Effects of ischemia and H₂O₂ on the cold stress protein CIRP expression in rat neuronal cells. Free Radic Biol Med, 1999, 27(11-12): 1238-1244.
12. Xia ZP, Zheng XM, Zheng H, et al. Downregulation of cold-inducible RNA-binding protein activates mitogen-activated protein kinases and impairs spermatogenic function in mouse testes. Asian J Androl, 2012, 14(6): 884-889.
13. Sakurai T, Yada N, Watanabe T, et al. Cold-inducible RNA-binding protein promotes the development of liver cancer. Cancer Sci, 2015, 106(4): 352-358.
14. Lu M, Ge Q, Wang G, et al. CIRBP is a novel oncogene in human bladder cancer inducing expression of HIF-1α. Cell Death Dis, 2018, 9(10): 1046.
15. Guo X, Wu Y, Hartley RS. Cold-inducible RNA-binding protein contributes to human antigen R and cyclin E1 deregulation in breast cancer. Mol Carcinog, 2010, 49(2): 130-140.
16. Hamid AA, Mandai M, Fujita J, et al. Expression of cold-inducible RNA-binding protein in the normal endometrium, endometrial hyperplasia, and endometrial carcinoma. Int J Gynecol Pathol, 2003, 22(3): 240-247.
17. 杨柳, 熊吟, 余永红, 等. 上调 CIRBP 基因表达抑制肾癌细胞的增殖和迁移及其可能的分子机制. 肿瘤, 2020, 40(4): 257-265.
18. Lujan DA, Ochoa JL, Hartley RS. Cold-inducible RNA binding protein in cancer and inflammation. Wiley Interdiscip Rev RNA, 2018, 9(2).
19. Brochu C, Cabrita MA, Melanson BD, et al. NF-κB-dependent role for cold-inducible RNA binding protein in regulating interleukin 1β. PLoS One, 2013, 8(2): e57426.
20. Chen L, Ran D, Xie W, et al. Cold-inducible RNA-binding protein mediates cold air inducible airway mucin production through TLR4/NF-κB signaling pathway. Int Immunopharmacol, 2016, 39: 48-56.
21. Idrovo JP, Jacob A, Yang WL, et al. A deficiency in cold-inducible RNA-binding protein accelerates the inflammation phase and improves wound healing. Int J Mol Med, 2016, 37(2): 423-428.
22. Gao S, Ma JJ, Lu C. Prognostic value of cyclin E expression in breast cancer: A meta-analysis. Tumour Biol, 2013, 34(6): 3423-3430.
23. Indacochea A, Guerrero S, Ureña M, et al. Cold-inducible RNA binding protein promotes breast cancer cell malignancy by regulating Cystatin C levels. RNA, 2021, 27(2): 190-201.
24. Dankner M, Caron M, Al-Saadi T, et al. Invasive growth associated with cold-inducible RNA-binding protein expression drives recurrence of surgically resected brain metastases. Neuro Oncol, 2021: noab002.
25. Xu C, Ke D, Zou L, et al. Cold-induced RNA-binding protein (CIRBP) regulates the expression of Src-associated during mitosis of 68 kDa (Sam68) and extracellular signal-regulated kinases (ERK) during heat stress-induced testicular injury. Reprod Fertil Dev, 2020, 32(18): 1357-1364.
26. Masuda T, Itoh K, Higashitsuji H, et al. Cold-inducible RNA-binding protein (Cirp) interacts with Dyrk1b/Mirk and promotes proliferation of immature male germ cells in mice. Proc Natl Acad Sci U S A, 2012, 109(27): 10885-10890.
27. Zhang Q, Wang YZ, Zhang W, et al. Involvement of cold inducible rna-binding protein in severe hypoxia-induced growth arrest of neural stem cells in vitro. Mol Neurobiol, 2017, 54(3): 2143-2153.
28. Qian X, Song X, He Y, et al. CCNB2 overexpression is a poor prognostic biomarker in Chinese NSCLC patients. Biomed Pharmacother, 2015, 74: 222-227.
29. Wang X, Xiao H, Wu D, et al. miR-335-5p regulates cell cycle and metastasis in lung adenocarcinoma by targeting CCNB2. Onco Targets Ther, 2020, 13: 6255-6263.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Expression and clinical significance of cold-induced RNA-binding protein in lung adenocarcinoma analyzed based on bioinformatics

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content