The clinicopathological and prognostic significance of PD-1 expression in cancers: A bioinformatics analysis
Background: Programmed cell death protein 1 (PD-1), which is encoded by PDCD1 gene, is a cell-surface protein of immunoglobin family. A number of published studies have reported the relationship between PD-1 expression and prognosis in cancers. The purpose of our study was to identify an independent prognostic marker.
Methods: In the present study, we investigated the prognostic value of PD-1 mRNA expression through the Kaplan–Meier plotter databases.
Results: The expression of PD-1 mRNA was negatively related with the overall survival (OS) rate of gastric cancer, but positively associated with the OS rate of breast cancer, ovarian cancer and liver cancer (P < 0.05). High PD-1 mRNA expression was linked to an improved relapse-free survival rate of breast cancer, ovarian cancer, and liver cancer (P < 0.05). There was a negative correlation with post-progression survival in gastric cancer (P < 0.05). Besides, there was a positive correlation with progression-free survival and disease specific survival in liver cancer. We also further evaluated the prognostic value of PD-1 in relation to different clinicopathological features of cancers.
Conclusion: Our results showed that PD-1 expression might be a good marker for the prognosis of patients with cancers, which highlights new methods and ideas for preventive treatment.
Okazaki T, Honjo T, 2007, PD-1 and PD-1 ligands: From discovery to clinical application. Int Immunol, 19(7): 813–824. https://doi.org/10.1093/intimm/dxm057
Pedoeem A, Azoulay-Alfaguter I, Strazza M, et al., 2014, Programmed death-1 pathway in cancer and autoimmunity. Clin Immunol, 153(1): 145–152. https://doi.org/10.1016/j.clim.2014.04.010
Mamalis A, Garcha M, Jagdeo J, 2014, Targeting the PD-1 pathway: A promising future for the treatment of melanoma. Arch Dermatol Res, 306(6): 511–519. https://doi.org/10.1007/s00403-014-1457-7
Eto S, Yoshikawa K, Nishi M, et al., 2016, Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection. Gastric Cancer, 19(2): 466–471. https://doi.org/10.1007/s10120-015-0519-7
Choi C, Yoo GS, Cho WK, et al., 2019, Optimizing radiotherapy with immune checkpoint blockade in hepatocellular carcinoma. World J Gastroenterol, 25(20): 2416–2429. https://doi.org/10.3748/wjg.v25.i20.2416
Greenwald RJ, Freeman GJ, Sharpe AH, 2005, The B7 family revisited. Ann Rev Immunol, 23(1): 515–548. https://doi.org/10.1146/annurev.immunol.23.021704.115611
Tumeh PC, Harview CL, Yearley JH, et al., 2014, PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature, 515(7528): 568–571. https://doi.org/10.1038/nature13954
Xu C, Hua HJ, Chen TY, et al., 2016, Progression of PD-1/ PD-L1 pathway in non-small cell lung cancer. Chin J Pathol, 45(9): 663–666.
Kang MJ, Kim KM, Bae JS, et al., 2013, Tumor-infiltrating PD1-positive lymphocytes and foxp3-positive regulatory T cells predict distant metastatic relapse and survival of clear cell renal cell carcinoma. Transl Oncol, 6(3): 282–289. https://doi.org/10.1593/tlo.13256
Raptopoulou AP, Bertsias G, Makrygiannakis D, et al., 2014, The programmed death 1/programmed death ligand 1 inhibitory pathway is up-regulated in rheumatoid synovium and regulates peripheral T cell responses in human and murine arthritis. Arthritis Rheumatol, 62(7): 1870–1880. https://doi.org/10.1002/art.27500
Hou JY, Xiang NY, Chen SF, et al., 2015, Expression of Foxp3 +Tregs and PD1 in gastric cancer tissues and their correlation with clinicopathological factors and prognosis. Chin. J. Pathophysiol., 10: 1744–1749.
Zhao WJ, Tan YL, Jia L, 2015, Expression of PD-1 in breast cancer and its clinical significance. Health, 2015(2): 37–37.
Thompson RH, Dong H, Lohse CM, et al., 2007, PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res, 13(6): 1757–1761. https://doi.org/10.1158/1078-0432.ccr-06-2599
Yang S, Zhang YH, Sun YL, et al., 2016, Expressions of programmed death 1, programmed death ligand-1 and nerve growth factor in liver cancer tissues and their significance. Infect Dis Inf, 29(2): 92–96.
Liu TM, Song Z, Wang WH, et al, 2019, Expression of GPC1 and PD-1 in non-small cell lung cancer tissues and their correlation with patient prognosis. Chin J Gerontol, 39(8): 66–68.
Shao JY, 2015, Research update on PD-1 and its ligand PD-L1 in malignant tumor. J Int Oncol, 42(5): 358–360.
Abhisek SW, Hammond WA and Joseph RW, 2015, Current state of anti-PD-L1 and anti-PD-1 agents in cancer therapy. Mol Immunol, 67(2 Pt A): 4–17. https://doi.org/10.1016/j.molimm.2015.02.009
Zhong YC, Lu X, Yang Y, et al., 2019, The expression and value of PD-1, PDL-1 and T lymphocyte subsets in breast cancer. Chongqing Yixue, 2019(18): 3134–3137.
Justin L, Tze-Chen H, Dorota HH, et al., 2018, Upregulation of PD-L1 expression by resveratrol and piceatannol in breast and colorectal cancer cells occurs via HDAC3/p300-mediated NF-κB signaling. Int J Oncol, 53(4): 1469–1480. https://doi.org/10.3892/ijo.2018.4512
Jia XP, Meng LL, Li HL, et al., 2021, Differential expression and clinical significance of PD-1, PD-L1 and FOXP3 in triple-negative breast cancer and non-triple-negative breast cancer tissues. J Med Inf, 34: 7–11. https://doi.org/10.1016/j.clbc.2018.05.006
Yu XQ, Zhang SW, Chen F, et al., 2019, Detection and significance of Tim-3 and PD-1 expression levels on the surface of PBMCs in peripheral blood of patients with HBV-related liver diseases. China J Mod Med, 69(7): 43–47.
Nebbia G, Peppa D, Schurich A, et al., 2012, Upregulation of the tim-3/galectin-9 pathway of T cell exhaustion in chronic hepatitis B virus infection. PLoS One, 7(10): e47648. https://doi.org/10.1371/journal.pone.0047648
Zhou QS, Wei Z, Du JH, 2019, Changes and clinical significance of expression of PD-1,PD-L1 and CEA 125 in primary hepatocellular carcinoma. Mod Digest Intervent, 24(8): 851–854.
Li PY, Ke XL, Zhu Q, et al., 2013, Expression and clinical significance of nerve growth factor in primary liver cancer. Chin J Hepatol, 21(2): 121–124.
Hu JW, Zhang XJ, Cai GY, et al., 2021, The expression and clinical significance of PD-1 and IFN-γ in peripheral blood of patients with primary hepatic carcinoma. Mod Med J, 49(7): 4.
Tan D, Sheng L, Yi QH, 2018, Correlation of PD-1/PD-L1 polymorphisms and expressions with clinicopathologic features and prognosis of ovarian cancer. Cancer Biomark, 21(2): 287–297. https://doi.org/10.3233/cbm-170357
Du XL, Zhang DM, Xu H, et al., 2021, Relationship between the expression of PD-1, PD-L1 and Cyclin D1 protein and prognosis in ovarian cancer. J Mol Diagn Ther, 13(10): 1680–1684.
Zhu WW, 2017, Expression of PD-1 and PD-L1 in gastric cancer tissues and its clinical significance. Henan Med Res, 26(18): 3302–3304.
Wu S, Shao JY, Wang F, et al., 2015, Expression and clinical significance of PD-L1 and PD-1 in gastric carcinoma. Acta Univ Med, 6: 103–107.
Li YF, Bao F, Xiang Y, et al., 2018, Expression of PD1/ PD-L1 in gastric carcinoma and its correlation with clinicopathological characteristics and prognosis. Chin J Clin Exp Pathol, 34: 614–618.
Deng Y, Ma YT, 2021, The expression of PD-1/PD-L1 in gastric cancer and its clinical significance. Mod Med J, 34(14): 4.
Feng TB, 2019, The expression and pathological significance of PD-L1 and PD-1 in gastric cancer. Mod Diagn Treatment, 30(6): 849–851.
Takaya S, Saito H and Ikeguchi M. Upregulation of immune checkpoint molecules, PD-1 and LAG-3, on CD4+ and CD8+ T cells after gastric cancer surgery. Yonago Acta Medica, 58(1): 39–44.
Qu HW, Jin JP, Chang T, 2019, Expression and clinical significance of PDCD1 in nasopharyngeal carcinoma tissues. Chin Clin Oncol, 24(4): 21–26.
Shi HJ, Li JR, Yan QJ, et al., 2019, Expression and clinical significance of PD-1,PD- L1 and TIM-3 in oral squamous cell carcinoma. Henan Med Res, 28(11): 1924–1926.
Ansell SM, Lesokhin AM, Borrello I, et al., 2015, PD-1 blockade with nivolumab in relapseed or refractory Hodgkin’s lynphoma. N Engl J Med, 372(4): 311–319.
Mezache L, Paniccia B, Nyinawabera A, et al., 2015, Enhanced expression of PD L1 in cervical intraepithelial neoplasia and cervical cancers. Mod Pathol, 28(12): 1594–602. https://doi.org/10.1038/modpathol.2015.108
Powles T, Eder JP, Fine GD, et al., 2014, MPDL3280A (anti- PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature, 515(7528): 558–562. https://doi.org/10.1038/nature13904
Starke A, Lindenmeyer MT, Segerer S, et al., 2010, Renal tubular PD-L1 (CD274) suppresses alloreactive human T-cell responses. Kidney Int, 78(1): 38–47. https://doi.org/10.1038/ki.2010.97
Wolchok JD, Kluger H, Callahan MK, et al., 2013, Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med, 369(2): 122–133.