Prognostic value of PHF19 mRNA expression in non-small-cell lung cancer: an analysis based on GEO_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LI Liying , QIN Huiping , HUANG Bin , QIN Chaoqun , XIAO Ying , TANG Yanping , HUANG Hancan ,  GAO Feng

Department of Respiratory and Critical Care Medicine, Guilin People’s Hospital, Guilin, Guangxi 541002, P. R. China;

Corresponding author：

GAO Feng, Email: 2020484210@qq.com

Keywords：

Non-small cell lung cancer; PHD finger protein 19; gene chip; prognostic analysis; immune infiltration

DOI：

10.7507/1671-6205.202503050

Video：

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Objective To analyze the expression and prognostic value of PHD Finger Protein 19 (PHF19) in non-small cell lung cancer (NSCLC) based on gene chip data. Methods The data about The Cancer Genome Atlas (TCGA) lung cancer patients were downloaded to analyze the expression of PHF19 in lung cancer. The data sets GSE30219 and GSE50081 were downloaded from the Gene Expression Omnibus (GEO), and the patients were screened into the training set and the validation set respectively, thus analyzing the relationship between PHF19 expression, gender, age, tumor clinical stage, pathological type and disease-free survival (DFS), as well as their relationship with overall survival (OS). Gene Ontology (GO)-Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and immune infiltration analysis were performed on PHF19 and co-expression related genes in lung cancer patients through the online database. Results The data from TCGA and GEO showed PHF19 was highly expressed in lung cancer (P<0.001), and PHF19 expression was related to tumor stage. The NSCLC patients in the PHF19 low expression group had longer DFS and OS than those in the high expression group (P<0.05). Multivariate COX regression analysis showed PHF19 was an independent prognostic factor in NSCLC patients (P<0.05). A nomogram drawing to predict the survival rate of lung cancer patients and verifying the C index showed the model has good accuracy. Gene enrichment analysis showed PHF19 high expression is mainly related to the cell cycle, cell nucleus, chromatin, etc. Immune infiltration analysis showed PHF19 is closely related to immune cell infiltration. Conclusions PHF19 can be used as an indicator to predict the prognosis of NSCLC. PHF19 high expression is an independent predictor of poor prognosis of NSCLC and may be a new target for its treatment.

Citation： LI Liying, QIN Huiping, HUANG Bin, QIN Chaoqun, XIAO Ying, TANG Yanping, HUANG Hancan, GAO Feng. Prognostic value of PHF19 mRNA expression in non-small-cell lung cancer: an analysis based on GEO. Chinese Journal of Respiratory and Critical Care Medicine, 2025, 24(9): 636-645. doi: 10.7507/1671-6205.202503050 Copy

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13.	Li QL, Lin X, Yu YL, et al. Genome-wide profiling in colorectal cancer identifies PHF19 and TBC1D16 as oncogenic super enhancers. Nat Commun, 2021, 12(1): 6407.
14.	Li P, Sun J, Ruan Y, et al. High PHD Finger Protein 19 (PHF19) expression predicts poor prognosis in colorectal cancer: a retrospective study. Peer J, 2021, 9: e11551.
15.	Tang Z, Kang B, Li C, et al. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res, 2019, 47(W1): W556-W560.
16.	Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia, 2017, 19(8): 649-658.
17.	Vasaikar SV, Straub P, Wang J, et al. LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res, 2018, 46(D1): D956-D963.
18.	Li T, Fan J, Wang B, et al. TIMER: A web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res, 2017, 77(21): e108-e110.
19.	Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res, 2013, 41 (Database issue): D991-D995.
20.	Parreno V, Martinez AM, Cavalli G. Mechanisms of polycomb group protein function in cancer. Cell Res, 2022, 32(3): 231-253.
21.	Hisanaga T, Romani F, Wu S, et al. The Polycomb repressive complex 2 deposits H3K27me3 and represses transposable elements in a broad range of eukaryotes. Curr Biol, 2023, 33(20): 4367-4380. e9.
22.	Fischer S, Liefke R. Polycomb-like proteins in gene regulation and cancer. Genes (Basel), 2023, 14(4): 938.
23.	Xu Y, Liu W, Jiang X, et al. Regulation of hPCL3 isoforms’ ubiquitination by TRIM21 in non-small cell lung cancer progression. Life Sci Alliance, 2023, 6(10): e202302060.
24.	de Visser KE, Joyce JA. The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth. Cancer Cell, 2023, 41(3): 374-403.
25.	Zhu ZY, Tang N, Wang MF, et al. Comprehensive pan-cancer genomic analysis reveals PHF19 as a carcinogenic indicator related to immune infiltration and prognosis of hepatocellular carcinoma. Front Immunol, 2022, 12: 781087.
26.	Ruan S, Zhang H, Tian X, et al. PHD Finger protein 19 enhances the resistance of ovarian cancer cells to compound fuling granule by protecting cell growth, invasion, migration, and stemness. Front Pharmacol, 2020, 11: 150.

1. 刘宗超, 李哲轩, 张阳, 等. 2020全球癌症统计报告解读. 肿瘤综合治疗电子杂志, 2021, 7(2): 1-14.
2. 国家卫生健康委办公厅. 原发性肺癌诊疗指南(2022年版). 协和医学杂志, 2022, 13(4): 549-570.
3. Song KJ, Choi S, Kim K, et al. Proteogenomic analysis reveals non-small cell lung cancer subtypes predicting chromosome instability, and tumor microenvironment. Nat Commun, 2024, 15(1): 10164.
4. 刘显平, 李晓, 杨帆. 非小细胞肺癌根治性切除术后复发转移模式研究进展. 中国肺癌杂志, 2022, 25(1): 8.
5. 朱玲玲, 伍娟, 王艇, 等. 2023年第2版NCCN肺癌筛查临床实践指南更新解读. 实用肿瘤杂志, 2023, 38(5): 399-407.
6. Riely GJ, Wood DE, Ettinger DS, et al. Non-small cell lung cancer, Version 4. 2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 2024, 22(4): 249-274.
7. Chen S, Wang Z, Sun B. Chinese Society of Clinical Oncology Non-Small Cell Lung Cancer (CSCO NSCLC) Guidelines in 2024: key update on the management of early and locally advanced NSCLC. Cancer Biol Med, 2025, 22(3): 191-196.
8. Goleij P, Heidari MM, Tabari MAK, et al. Polycomb repressive complex 2 (PRC2) pathway’s role in cancer cell plasticity and drug resistance. Funct Integr Genomics, 2025, 25(1): 53.
9. Xiaoyun S, Yuyuan Z, Jie X, et al. PHF19 activates hedgehog signaling and promotes tumorigenesis in hepatocellular carcinoma. Exp Cell Res, 2021, 406(1): 112690.
10. Schinke CD, Bird JT, Qu P, et al. PHF19 inhibition as a therapeutic target in multiple myeloma. Curr Res Transl Med, 2021, 69(3): 103290.
11. Johnson TS, Sudha P, Liu E, et al. 1q amplification and PHF19 expressing high-risk cells are associated with relapsed/refractory multiple myeloma. Nat Commun, 2024, 15(1): 4144. Published 2024 May 16.
12. An H, Chen S, Zhang X, et al. PHF19 before and post induction treatment possess favorable potency of reflecting treatment response to protease inhibitors, event-free survival, and overall survival in multiple myeloma patients. Hematology, 2024, 29(1): 2331389.
13. Li QL, Lin X, Yu YL, et al. Genome-wide profiling in colorectal cancer identifies PHF19 and TBC1D16 as oncogenic super enhancers. Nat Commun, 2021, 12(1): 6407.
14. Li P, Sun J, Ruan Y, et al. High PHD Finger Protein 19 (PHF19) expression predicts poor prognosis in colorectal cancer: a retrospective study. Peer J, 2021, 9: e11551.
15. Tang Z, Kang B, Li C, et al. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res, 2019, 47(W1): W556-W560.
16. Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia, 2017, 19(8): 649-658.
17. Vasaikar SV, Straub P, Wang J, et al. LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res, 2018, 46(D1): D956-D963.
18. Li T, Fan J, Wang B, et al. TIMER: A web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res, 2017, 77(21): e108-e110.
19. Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res, 2013, 41 (Database issue): D991-D995.
20. Parreno V, Martinez AM, Cavalli G. Mechanisms of polycomb group protein function in cancer. Cell Res, 2022, 32(3): 231-253.
21. Hisanaga T, Romani F, Wu S, et al. The Polycomb repressive complex 2 deposits H3K27me3 and represses transposable elements in a broad range of eukaryotes. Curr Biol, 2023, 33(20): 4367-4380. e9.
22. Fischer S, Liefke R. Polycomb-like proteins in gene regulation and cancer. Genes (Basel), 2023, 14(4): 938.
23. Xu Y, Liu W, Jiang X, et al. Regulation of hPCL3 isoforms’ ubiquitination by TRIM21 in non-small cell lung cancer progression. Life Sci Alliance, 2023, 6(10): e202302060.
24. de Visser KE, Joyce JA. The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth. Cancer Cell, 2023, 41(3): 374-403.
25. Zhu ZY, Tang N, Wang MF, et al. Comprehensive pan-cancer genomic analysis reveals PHF19 as a carcinogenic indicator related to immune infiltration and prognosis of hepatocellular carcinoma. Front Immunol, 2022, 12: 781087.
26. Ruan S, Zhang H, Tian X, et al. PHD Finger protein 19 enhances the resistance of ovarian cancer cells to compound fuling granule by protecting cell growth, invasion, migration, and stemness. Front Pharmacol, 2020, 11: 150.

Chinese Journal of Respiratory and Critical Care Medicine

Prognostic value of PHF19 mRNA expression in non-small-cell lung cancer: an analysis based on GEO

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