Pan-cancer Analysis Predicts PDCD4 as a Potential Diagnostic, Prognostic and Immune Infiltration-related Biomarker
-
Haili Jiang
,
Anni Xie
,
Ting Wang
,
Wenjing Shi
,
Die Hu
,
Rui Sheng
,
Chaozheng Gao
,
Tian Xie
Abstract
Programmed cell death protein 4 (PDCD4) is an oncogene involved in the cell cycle and apoptosis, enhancing drug sensitivity in tumor cells and inhibiting tumor development. However, the relationship between PDCD4 and tumor immune microenvironment remains unclear.
The Cancer Genome Atlas (TCGA) database was used to collect PDCD4 data and somatic mutation data for 33 cancer types. Gene Expression Profiling Interactive Analysis (GEPIA) database was used to obtain the distribution map of PDCD4 gene in human tissues and the prognostic expression heat map of cancer. Human Protein Atlas (HPA) database was used to explore the expression differences of PDCD4 RNA in different cell lines, and PDCD4 expression and clinical data were obtained from Gene Expression Omnibus (GEO) database.
We found significant differences in the expression of PDCD4 in different cancers and associated with patient prognosis. PDCD4 is closely related to the tumor microenvironment, sensitive to immunomodulators, and involved in immune regulation. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that PDCD4 plays a crucial role in tumor metastasis, affecting the survival and prognosis of tumor patients. The differential expression of PDCD4 in various tumor tissues and its involvement in immunomodulatory mechanisms suggest its potential as a biomarker for prognosis and immunotherapy.
PDCD4 was closely related to tumor immune microenvironment and immune efficacy indexes. It is suggested that it may be used as a biomarker to predict immune efficacy.
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24. Doos WG, Saravis CA, Pusztaszeri G, Burke B, Oh SK, Zamcheck N, et al. Tissue localization of zinc glycinate marker and carcinoembryonic antigen by immunofluorescence. II. Immunofluorescence microscopy. Jnci-J Natl Cancer I. 1978;60(6):1375-82.
25. Tran TT, Rane CK, Zito CR, Weiss SA, Jessel S, Lucca L, et al. Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells. Cancers. 2021;13(5)
26. Braun C, Katholnig K, Kaltenecker C, Linke M, Sukhbaatar N, Hengstschlager M, et al. p38 regulates the tumor suppressor PDCD4 via the TSC-mTORC1 pathway. Cell Stress. 2021;5(12):176-82.
27. Lai CY, Yeh KY, Liu BF, Chang TM, Chang CH, Liao YF, et al. MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-alpha Signaling Pathways in Zebrafish. Cancers. 2021;13(21):5565.
28. Zhou J, Li H, Li N, Li X, Zhang H, Song Q, et al. MicroRNA-641 inhibits lung cancer cells proliferation, metastasis but promotes apoptosis in cells by targeting PDCD4. Int J Clin Exp Patho. 2017;10(8):8211-21.
29. Guo LM, Ding GF, Xu WC, Ge H, Jiang Y, Lu YF. Anti-PD-L1 Antibody Enhances T Cell Immune Responses and Reduces Resistance of Breast Cancer Cells to Radiotherapy. Oxid Med Cell Longev. 2022;2022:5938688.
2. Deng H, Yu B, Li Y. Tanshinone IIA alleviates acute ethanol-induced myocardial apoptosis mainly through inhibiting the expression of PDCD4 and activating the PI3K/Akt pathway. Phytother Res. 2021;35(8):4309-23.
3. Pan J, Wang B, Pu X, Qiu C, Li D, Wu Z, et al. lncRNA GAPLINC regulates vascular endothelial cell apoptosis in atherosclerosis. Arch Med Sci. 2024;20(1):216-32.
4. Gonzalez-Ortiz A, Pulido-Capiz A, Castaneda-Sanchez CY, Ibarra-Lopez E, Galindo-Hernandez O, Calderon-Fernandez MA, et al. eIF4A/PDCD4 Pathway, a Factor for Doxorubicin Chemoresistance in a Triple-Negative Breast Cancer Cell Model. Cells-Basel. 2022;11(24):4069.
5. Chen X, Guan Y, Zhang Y, Jia Y, Li W, Guo C, et al. Programmed cell death 4 modulates lysosomal function by inhibiting TFEB translation. Cell Death Differ. 2021;28(4):1237-50.
6. Li JZ, Gao W, Ho WK, Lei WB, Wei WI, Chan JY, et al. The clinical association of programmed cell death protein 4 (PDCD4) with solid tumors and its prognostic significance: a meta-analysis. Chin J Cancer. 2016;35(1):95.
7. Fan Q, Lu Q, Wang G, Zhu W, Teng L, Chen W, et al. Optimizing component formula suppresses lung cancer by blocking DTL-mediated PDCD4 ubiquitination to regulate the MAPK/JNK pathway. J Ethnopharmacol. 2022;299:115546.
8. Huang WC, Yadav VK, Cheng WH, Wang CH, Hsieh MS, Huang TY, et al. The MEK/ERK/miR-21 Signaling Is Critical in Osimertinib Resistance in EGFR-Mutant Non-Small Cell Lung Cancer Cells. Cancers. 2021;13(23):6005.
9. Ge Y, Xia T, Feng Z, Xi Y, Hu D, Hong Y, et al. Knockdown of programmed cell death factor 4 restores erectile function by attenuating apoptosis in rats with bilateral cavernous nerve crush injury. Andrology-Us. 2024;
10. Chen Q, Lu H, Duan C, Zhu X, Zhang Y, Li M, et al. PDCD4 Simultaneously Promotes Microglia Activation via PDCD4-MAPK-NF-kappaB Positive Loop and Facilitates Neuron Apoptosis During Neuroinflammation. Inflammation. 2022;45(1):234-52.
11. Zhu F, Zhang X, Wen J, Liu Y, Zhu Y. Celastrus orbiculatus extract reverses precancerous lesions of gastric cancer by inhibiting autophagy via regulating the PDCD4-ATG5 signaling pathway. J Pharm Pharmacol. 2024;76(3):257-68.
12. Mondin A, Bertazza L, Barollo S, Pedron MC, Manso J, Piva I, et al. Validation of miRNAs as diagnostic and prognostic biomarkers, and possible therapeutic targets in medullary thyroid cancers. Front Endocrinol. 2023;14:1151583.
13. Farasati FB, Vakili K, Fathi M, Yaghoobpoor S, Bhia M, Naimi-Jamal MR. The role of microRNA-21 (miR-21) in pathogenesis, diagnosis, and prognosis of gastrointestinal cancers: A review. Life Sci. 2023;316:121340.
14. Huckabay LM, Anderson N, Holm DM, Lee J. Cognitive, affective, and transfer of learning consequences of computer-assisted instruction. Nurs Res. 1979;28(4):228-33.
15. Kim JY, Lee H, Kim EK, Lee WM, Hong YO, Hong SA. Low PDCD4 Expression Is Associated With Poor Prognosis of Colorectal Carcinoma. Appl Immunohisto M M. 2021;29(9):685-92.
16. Cai Q, Yang HS, Li YC, Zhu J. Dissecting the Roles of PDCD4 in Breast Cancer. Front Oncol. 2022;12:855807.
17. Tang H, Chen Y, Zhang N, Deng J, Zhou K. Higher expression of programmed cell death 4 (PDCD4) in acute myeloid leukemia is associated with better prognosis after chemotherapy. Ann Hematol. 2023;102(12):3401-12.
18. Geng X, Li Y, Sun Y, Cao L, Song Z. MicroRNA-181b-5p Facilitates Thyroid Cancer Growth via Targeting Programmed Cell Death 4. Mol Biotechnol. 2024;66(5):1154-64.
19. Duan X, Li W, Hu P, Jiang B, Yang J, Zhou L, et al. MicroRNA-183-5p contributes to malignant progression through targeting PDCD4 in human hepatocellular carcinoma. Bioscience Rep. 2020;40(10):BSR20201761.
20. Ding X, Cheng X, Gong M, Chen X, Yin F, Lai K. Hypermethylation and Expression Silencing of PDCD4 Gene in Hepatocellular Carcinoma: A Consort Study. Medicine. 2016;95(6):e2729.
21. Qiu X, Wei Y, Liu C, Ding C, Zhao S. Hyperandrogen enhances apoptosis of human ovarian granulosa cells via up-regulation and demethylation of PDCD4. Gynecol Endocrinol. 2020;36(4):333-7.
22. Wen YH, Shi X, Chiriboga L, Matsahashi S, Yee H, Afonja O. Alterations in the expression of PDCD4 in ductal carcinoma of the breast. Oncol Rep. 2007;18(6):1387-93.
23. Yang SY, Hu Y, Zhao R, Zhou YN, Zhuang Y, Zhu Y, et al. Quercetin-loaded mesoporous nano-delivery system remodels osteoimmune microenvironment to regenerate alveolar bone in periodontitis via the miR-21a-5p/PDCD4/NF-kappaB pathway. J Nanobiotechnol. 2024;22(1):94.
24. Doos WG, Saravis CA, Pusztaszeri G, Burke B, Oh SK, Zamcheck N, et al. Tissue localization of zinc glycinate marker and carcinoembryonic antigen by immunofluorescence. II. Immunofluorescence microscopy. Jnci-J Natl Cancer I. 1978;60(6):1375-82.
25. Tran TT, Rane CK, Zito CR, Weiss SA, Jessel S, Lucca L, et al. Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells. Cancers. 2021;13(5)
26. Braun C, Katholnig K, Kaltenecker C, Linke M, Sukhbaatar N, Hengstschlager M, et al. p38 regulates the tumor suppressor PDCD4 via the TSC-mTORC1 pathway. Cell Stress. 2021;5(12):176-82.
27. Lai CY, Yeh KY, Liu BF, Chang TM, Chang CH, Liao YF, et al. MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-alpha Signaling Pathways in Zebrafish. Cancers. 2021;13(21):5565.
28. Zhou J, Li H, Li N, Li X, Zhang H, Song Q, et al. MicroRNA-641 inhibits lung cancer cells proliferation, metastasis but promotes apoptosis in cells by targeting PDCD4. Int J Clin Exp Patho. 2017;10(8):8211-21.
29. Guo LM, Ding GF, Xu WC, Ge H, Jiang Y, Lu YF. Anti-PD-L1 Antibody Enhances T Cell Immune Responses and Reduces Resistance of Breast Cancer Cells to Radiotherapy. Oxid Med Cell Longev. 2022;2022:5938688.
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How to Cite
1.
Jiang H, Xie A, Wang T, Shi W, Hu D, Sheng R, Gao C, Xie T. Pan-cancer Analysis Predicts PDCD4 as a Potential Diagnostic, Prognostic and Immune Infiltration-related Biomarker. Iran J Allergy Asthma Immunol. 2025;:1-21.
