Frontiers in Medical Science Research, 2024, 6(10); doi: 10.25236/FMSR.2024.061002.
Min He1, Jianxin Lyu2
1College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
2Key Laboratory of Laboratory Medicine, Ministry of Education, College of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
CEBPB is an important transcription factor involved in the immune regulation of inflammatory diseases, and chronic inflammation is a key factor in cancer progression. CEBPB has been found to influence the occurrence and development of various malignancies in aspects such as cellular metabolism, drug resistance, migration, and invasion. However, its role in non-small cell lung cancer (NSCLC) remains unclear. To address this issue, this study analyzed the prognostic value of CEBPB in NSCLC and its relationship with clinical pathological parameters using the GEPIA 2, UALCAN, Human Protein Atlas, Kaplan-Meier Plotter, and c-BioPortal databases. It was found that CEBPB transcriptional expression is reduced in NSCLC patients and is significantly associated with cancer staging in LUAD patients and lymph node metastasis in LUSC patients. Additionally, higher CEBPB mRNA expression is significantly associated with shorter overall survival (OS) and disease-free survival (DFS) in NSCLC patients. Furthermore, the mutation rate of CEBPB in NSCLC patients is low at only 1%, but gene alterations of CEBPB are linked to shorter OS in NSCLC patients. In conclusion, these results suggest that CEBPB may serve as a biomarker for the survival prognosis of NSCLC patients.
CEBPB, NSCLC, Prognosis, GEPIA 2, UALCAN
Min He, Jianxin Lyu. CEBPB Transcriptional Expression as a Potential Indicator of Survival Prognosis in Non-Small Cell Lung Cancer Patients. Frontiers in Medical Science Research (2024), Vol. 6, Issue 10: 8-17. https://doi.org/10.25236/FMSR.2024.061002.
[1] BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2024, 74(3): 229-63.
[2] PARDOLL D M. The blockade of immune checkpoints in cancer immunotherapy [J]. Nat Rev Cancer, 2012, 12(4): 252-64.
[3] HIRSCH F R, SCAGLIOTTI G V, MULSHINE J L, et al. Lung cancer: current therapies and new targeted treatments [J]. Lancet, 2017, 389(10066): 299-311.
[4] ZOU W, CHEN L. Inhibitory B7-family molecules in the tumour microenvironment [J]. Nat Rev Immunol, 2008, 8(6): 467-77.
[5] HAN F, HE J, LI F, et al. Emerging Roles of MicroRNAs in EGFR-Targeted Therapies for Lung Cancer [J]. Biomed Res Int, 2015, 2015: 672759.
[6] ANDREWS L P, YANO H, VIGNALI D A A. Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: breakthroughs or backups [J]. Nat Immunol, 2019, 20(11): 1425-34.
[7] HANAHAN D, WEINBERG R A. Hallmarks of cancer: the next generation [J]. Cell, 2011, 144(5): 646-74.
[8] HERBST R S, MORGENSZTERN D, BOSHOFF C. The biology and management of non-small cell lung cancer [J]. Nature, 2018, 553(7689): 446-54.
[9] ZHANG J, FUJIMOTO J, ZHANG J, et al. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing [J]. Science, 2014, 346(6206): 256-9.
[10] MOLINA J R, YANG P, CASSIVI S D, et al. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship [J]. Mayo Clin Proc, 2008, 83(5): 584-94.
[11] TRAVIS W D, BRAMBILLA E, NOGUCHI M, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary [J]. Proc Am Thorac Soc, 2011, 8(5): 381-5.
[12] YANG M, LIN C, WANG Y, et al. Identification of a cytokine-dominated immunosuppressive class in squamous cell lung carcinoma with implications for immunotherapy resistance [J]. Genome Med, 2022, 14(1): 72.
[13] TSUKADA J, YOSHIDA Y, KOMINATO Y, et al. The CCAAT/enhancer (C/EBP) family of basic-leucine zipper (bZIP) transcription factors is a multifaceted highly-regulated system for gene regulation [J]. Cytokine, 2011, 54(1): 6-19.
[14] RAMJI D P, FOKA P. CCAAT/enhancer-binding proteins: structure, function and regulation [J]. Biochem J, 2002, 365(Pt 3): 561-75.
[15] ROY S K, HU J, MENG Q, et al. MEKK1 plays a critical role in activating the transcription factor C/EBP-beta-dependent gene expression in response to IFN-gamma [J]. Proc Natl Acad Sci U S A, 2002, 99(12): 7945-50.
[16] MA Y, CHEN Y, ZHAN L, et al. CEBPB-mediated upregulation of SERPINA1 promotes colorectal cancer progression by enhancing STAT3 signaling [J]. Cell Death Discov, 2024, 10(1): 219.
[17] LI W, TANIKAWA T, KRYCZEK I, et al. Aerobic Glycolysis Controls Myeloid-Derived Suppressor Cells and Tumor Immunity via a Specific CEBPB Isoform in Triple-Negative Breast Cancer [J]. Cell Metab, 2018, 28(1): 87-103 e6.
[18] OKAZAKI K, ANZAWA H, KATSUOKA F, et al. CEBPB is required for NRF2-mediated drug resistance in NRF2-activated non-small cell lung cancer cells [J]. J Biochem, 2022, 171(5): 567-78.
[19] TANG Z, KANG B, LI C, et al. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis [J]. Nucleic Acids Res, 2019, 47(W1): W556-W60.
[20] CHANDRASHEKAR D S, BASHEL B, BALASUBRAMANYA S A H, et al. UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses [J]. Neoplasia, 2017, 19(8): 649-58.
[21] ASPLUND A, EDQVIST P H, SCHWENK J M, et al. Antibodies for profiling the human proteome-The Human Protein Atlas as a resource for cancer research [J]. Proteomics, 2012, 12(13): 2067-77.
[22] WANG W, LIU P, ZHANG Y, et al. Expression and functions of transient receptor potential channels in liver diseases [J]. Acta Pharm Sin B, 2023, 13(2): 445-59.
[23] LIU Z L, BI X W, LIU P P, et al. Expressions and prognostic values of the E2F transcription factors in human breast carcinoma [J]. Cancer Manag Res, 2018, 10: 3521-32.
[24] CAO T, PAN W, SUN X, et al. Increased expression of TET3 predicts unfavorable prognosis in patients with ovarian cancer-a bioinformatics integrative analysis [J]. J Ovarian Res, 2019, 12(1): 101.
[25] HOU G X, LIU P, YANG J, et al. Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using Oncomine and Kaplan-Meier plotter [J]. PLoS One, 2017, 12(3): e0174515.
[26] HOU W, KONG L, HOU Z, et al. CD44 is a prognostic biomarker and correlated with immune infiltrates in gastric cancer [J]. BMC Med Genomics, 2022, 15(1): 225.
[27] GAO J, AKSOY B A, DOGRUSOZ U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal [J]. Sci Signal, 2013, 6(269): pl1.
[28] KINOSHITA S, AKIRA S, KISHIMOTO T. A member of the C/EBP family, NF-IL6 beta, forms a heterodimer and transcriptionally synergizes with NF-IL6 [J]. Proc Natl Acad Sci U S A, 1992, 89(4): 1473-6.
[29] KUZNETSOVA T, PRANGE K H M, GLASS C K, et al. Transcriptional and epigenetic regulation of macrophages in atherosclerosis [J]. Nat Rev Cardiol, 2020, 17(4): 216-28.
[30] LOPEZ-YRIGOYEN M, CASSETTA L, POLLARD J W. Macrophage targeting in cancer [J]. Ann N Y Acad Sci, 2021, 1499(1): 18-41.
[31] YANG J, XU Y, XIE K, et al. CEBPB is associated with active tumor immune environment and favorable prognosis of metastatic skin cutaneous melanoma [J]. Front Immunol, 2022, 13: 991797.
[32] REN Y, GUO W, QIAO B. Abnormal expression of CEBPB promotes the progression of renal cell carcinoma through regulating the generation of IL-6 [J]. Heliyon, 2023, 9(10): e20175.
[33] LU T, LI M, ZHAO M, et al. Metformin inhibits human non-small cell lung cancer by regulating AMPK-CEBPB-PDL1 signaling pathway [J]. Cancer Immunol Immunother, 2022, 71(7): 1733-46.
[34] SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2018 [J]. CA Cancer J Clin, 2018, 68(1): 7-30.
[35] 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 [J]. CA Cancer J Clin, 2018, 68(6): 394-424.
[36] ETTINGER D S, AKERLEY W, BORGHAEI H, et al. Non-small cell lung cancer, version 2.2013 [J]. J Natl Compr Canc Netw, 2013, 11(6): 645-53; quiz 53.
[37] OH H S, SMART R C. Expression of CCAAT/enhancer binding proteins (C/EBP) is associated with squamous differentiation in epidermis and isolated primary keratinocytes and is altered in skin neoplasms [J]. J Invest Dermatol, 1998, 110(6): 939-45.
[38] REGALO G, FORSTER S, RESENDE C, et al. C/EBPbeta regulates homeostatic and oncogenic gastric cell proliferation [J]. J Mol Med (Berl), 2016, 94(12): 1385-95.
[39] RASK K, THORN M, PONTEN F, et al. Increased expression of the transcription factors CCAAT-enhancer binding protein-beta (C/EBBeta) and C/EBzeta (CHOP) correlate with invasiveness of human colorectal cancer [J]. Int J Cancer, 2000, 86(3): 337-43.
[40] OYA M, HORIGUCHI A, MIZUNO R, et al. Increased activation of CCAAT/enhancer binding protein-beta correlates with the invasiveness of renal cell carcinoma [J]. Clin Cancer Res, 2003, 9(3): 1021-7.
[41] HOMMA J, YAMANAKA R, YAJIMA N, et al. Increased expression of CCAAT/enhancer binding protein beta correlates with prognosis in glioma patients [J]. Oncol Rep, 2006, 15(3): 595-601.
[42] RUSSELL A, BOONE B, JIANG A, et al. Genomic profiling of C/EBPbeta2 transformed mammary epithelial cells: a role for nuclear interleukin-1beta [J]. Cancer Biol Ther, 2010, 10(5): 509-19.
[43] ZAHNOW C A, YOUNES P, LAUCIRICA R, et al. Overexpression of C/EBPbeta-LIP, a naturally occurring, dominant-negative transcription factor, in human breast cancer [J]. J Natl Cancer Inst, 1997, 89(24): 1887-91.