Bioinformatics analysis of <i>POLD1</i> gene expression and biological function in non-small cell lung cancer_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

HE Mengyu , CHEN Ling , LI Nan ,  JIN Linling

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P. R. China;

Corresponding author：

JIN Linling, Email: cmu.apple@163.com

Keywords：

Non-small cell lung cancer; POLD1; prognosis; bioinformatics analysis

DOI：

10.7507/1671-6205.202301026

Video：

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Objective To detect the expression and clinical significance of POLD1 gene in non-small cell lung cancer (NSCLC) via bioinformatics method. Methods The expression difference of POLD1 in NSCLC tissue and normal lung tissue was investigated by TIMER database. UALCAN database was used to further verify different expression of POLD1 as well as the relationship between POLD1 expression and clinicopathological characteristics of NSCLC. The correlation between POLD1 gene and prognosis of NSCLC patients was detected by GEPIA and TIMER database. cBioPortal database was used to analyze frequencies of POLD1 gene mutation. POLD1-related protein-protein interaction network was constructed by STRING database. The relationship between POLD1 and immune infiltration was based on TISIDB database. Results The expression of POLD1 gene in lung adenocarcinoma and lung squamous cell carcinoma was significantly higher than that in normal lung tissue. In lung adenocarcinoma, patients with lower POLD1 level showed better prognosis. 1.2% of lung adenocarcinoma patients and 1.8% of lung squamous cell carcinoma patients carried mutated POLD1 gene, mainly missense mutations. POLD1 may interact with POLD2, POLD3, POLD4, POLE, RPA1, PCNA, MSH6, MSH2 and FEN1. The biological processes include DNA replication, mismatch repair, etc. Besides, the expression of POLD1 in NSCLC was correlated with the number of different immune cells. Conclusions The POLD1 gene is highly expressed in NSCLC patients, and negatively related with survival prognosis in patients of lung adenocarcinoma. POLD1 gene may be a potential diagnostic target and prognostic marker in NSCLC.

Citation： HE Mengyu, CHEN Ling, LI Nan, JIN Linling. Bioinformatics analysis of POLD1 gene expression and biological function in non-small cell lung cancer. Chinese Journal of Respiratory and Critical Care Medicine, 2023, 22(2): 104-110. doi: 10.7507/1671-6205.202301026 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.	Deshpand R, Chandra M, Rauthan A. Evolving trends in lung cancer: epidemiology, diagnosis, and management. Indian J Cancer, 2022, 59(Suppl 1): S90-S105.
3.	Chen PX, Liu YH, Wen YK, et al. Non-small cell lung cancer in China. Cancer Commun (Lond), 2022, 42(10): 937-970.
4.	Mur P, García-Mulero S, del Valle J, et al. Role of POLE and POLD1 in familial cancer. Genet Med, 2020, 22(12): 2089-2100.
5.	朱玉, 苏亚娟. DNA聚合酶ε在肿瘤中的研究进展. 实用肿瘤杂志, 2021, 36(2): 189-193.
6.	Hua X, Xu HM, Yang YN, et al. DrGaP: a powerful tool for identifying driver genes and pathways in cancer sequencing studies. Am J Hum Genet, 2013, 93(3): 439-451.
7.	Zhang LM, Chen JH, Yang H, et al. Multiple microarray analyses identify key genes associated with the development of non-small cell lung cancer from chronic obstructive pulmonary disease. J Cancer, 2021, 12(4): 996-1010.
8.	Yoshida R, Miyashita K, Inoue M, et al. Concurrent genetic alterations in DNA polymerase proofreading and mismatch repair in human colorectal cancer. Eur J Hum Genet, 2011, 19(3): 320-325.
9.	Wang F, Zhao Q, Wang YN, et al. Evaluation of POLE and POLD1 mutations as biomarkers for immunotherapy outcomes across multiple cancer types. JAMA Oncol, 2019, 5(10): 1504-1506.
10.	Tang H, You TT, Sun Z, et al. A comprehensive prognostic analysis of POLD1 in hepatocellular carcinoma. BMC Cancer, 2022, 22(1): 197.
11.	Qin QH, Tan QX, Li JY, et al. Elevated expression of POLD1 is associated with poor prognosis in breast cancer. Oncol Lett, 2018, 16(5): 5591-5598.
12.	Magrin L, Fanale D, Brando C, et al. POLE, POLD1, and NTHL1: the last but not the least hereditary cancer-predisposing genes. Oncogene, 2021, 40(40): 5893-5901.
13.	Nicolas E, Golemis EA, Arora S. POLD1: Central mediator of DNA replication and repair, and implication in cancer and other pathologies. Gene, 2016, 590(1): 128-141.
14.	Antoniali G, Marcuzzi F, Casarano E, et al. Cadmium treatment suppresses DNA polymerase δ catalytic subunit gene expression by acting on the p53 and Sp1 regulatory axis. DNA Repair (Amst), 2015, 35: 90-105.
15.	Sanefuji K, Taketomi A, Iguchi T, et al. Significance of DNA polymerase delta catalytic subunit p125 induced by mutant p53 in the invasive potential of human hepatocellular carcinoma. Oncology, 2010, 79(3-4): 229-237.
16.	宋勇. 晚期非小细胞肺癌的治疗. 中国呼吸与危重监护杂志, 2005, 4(3): 175-176.
17.	Liu XY, Wu SC, Yang YH, et al. The prognostic landscape of tumor-infiltrating immune cell and immunomodulators in lung cancer. Biomed Pharmacother, 2017, 95: 55-61.
18.	曾瑞红, 房桂珍, 魏林. CD4⁺ T细胞在肿瘤免疫治疗中的作用. 细胞生物学杂志, 2008, 30(1): 30-34.
19.	王琰, 卢斌峰, 蒋敬庭, 等. 肿瘤浸润淋巴细胞及其亚群在肿瘤免疫中的作用. 临床检验杂志, 2018, 36(11): 854-857.
20.	周越, 苑珩珩, 韩宇, 等. POLE/POLD1突变在肿瘤免疫治疗预后中的价值. 中国肿瘤, 2022, 31(3): 215-220.

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. Deshpand R, Chandra M, Rauthan A. Evolving trends in lung cancer: epidemiology, diagnosis, and management. Indian J Cancer, 2022, 59(Suppl 1): S90-S105.
3. Chen PX, Liu YH, Wen YK, et al. Non-small cell lung cancer in China. Cancer Commun (Lond), 2022, 42(10): 937-970.
4. Mur P, García-Mulero S, del Valle J, et al. Role of POLE and POLD1 in familial cancer. Genet Med, 2020, 22(12): 2089-2100.
5. 朱玉, 苏亚娟. DNA聚合酶ε在肿瘤中的研究进展. 实用肿瘤杂志, 2021, 36(2): 189-193.
6. Hua X, Xu HM, Yang YN, et al. DrGaP: a powerful tool for identifying driver genes and pathways in cancer sequencing studies. Am J Hum Genet, 2013, 93(3): 439-451.
7. Zhang LM, Chen JH, Yang H, et al. Multiple microarray analyses identify key genes associated with the development of non-small cell lung cancer from chronic obstructive pulmonary disease. J Cancer, 2021, 12(4): 996-1010.
8. Yoshida R, Miyashita K, Inoue M, et al. Concurrent genetic alterations in DNA polymerase proofreading and mismatch repair in human colorectal cancer. Eur J Hum Genet, 2011, 19(3): 320-325.
9. Wang F, Zhao Q, Wang YN, et al. Evaluation of POLE and POLD1 mutations as biomarkers for immunotherapy outcomes across multiple cancer types. JAMA Oncol, 2019, 5(10): 1504-1506.
10. Tang H, You TT, Sun Z, et al. A comprehensive prognostic analysis of POLD1 in hepatocellular carcinoma. BMC Cancer, 2022, 22(1): 197.
11. Qin QH, Tan QX, Li JY, et al. Elevated expression of POLD1 is associated with poor prognosis in breast cancer. Oncol Lett, 2018, 16(5): 5591-5598.
12. Magrin L, Fanale D, Brando C, et al. POLE, POLD1, and NTHL1: the last but not the least hereditary cancer-predisposing genes. Oncogene, 2021, 40(40): 5893-5901.
13. Nicolas E, Golemis EA, Arora S. POLD1: Central mediator of DNA replication and repair, and implication in cancer and other pathologies. Gene, 2016, 590(1): 128-141.
14. Antoniali G, Marcuzzi F, Casarano E, et al. Cadmium treatment suppresses DNA polymerase δ catalytic subunit gene expression by acting on the p53 and Sp1 regulatory axis. DNA Repair (Amst), 2015, 35: 90-105.
15. Sanefuji K, Taketomi A, Iguchi T, et al. Significance of DNA polymerase delta catalytic subunit p125 induced by mutant p53 in the invasive potential of human hepatocellular carcinoma. Oncology, 2010, 79(3-4): 229-237.
16. 宋勇. 晚期非小细胞肺癌的治疗. 中国呼吸与危重监护杂志, 2005, 4(3): 175-176.
17. Liu XY, Wu SC, Yang YH, et al. The prognostic landscape of tumor-infiltrating immune cell and immunomodulators in lung cancer. Biomed Pharmacother, 2017, 95: 55-61.
18. 曾瑞红, 房桂珍, 魏林. CD4⁺ T细胞在肿瘤免疫治疗中的作用. 细胞生物学杂志, 2008, 30(1): 30-34.
19. 王琰, 卢斌峰, 蒋敬庭, 等. 肿瘤浸润淋巴细胞及其亚群在肿瘤免疫中的作用. 临床检验杂志, 2018, 36(11): 854-857.
20. 周越, 苑珩珩, 韩宇, 等. POLE/POLD1突变在肿瘤免疫治疗预后中的价值. 中国肿瘤, 2022, 31(3): 215-220.

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