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Discover Oncology
Published in: Discover Oncology 1/2024

Open Access 01-12-2024 | Prostate Cancer | Research

Identifying the tumor immune microenvironment-associated prognostic genes for prostate cancer

Authors: Shi Zong, Ji Gao

Published in: Discover Oncology | Issue 1/2024

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Abstract

Purpose

This study aimed to explore novel tumor immune microenvironment (TIME)-associated biomarkers in prostate adenocarcinoma (PRAD).

Methods

PRAD RNA-sequencing data were obtained from UCSC Xena database as the training dataset. The ESTIMATE package was used to evaluate stromal, immune, and tumor purity scores. Differentially expressed genes (DEGs) related to TIME were screened using the immune and stromal scores. Gene functions were analyzed using DAVID. The LASSO method was performed to screen prognostic TIME-related genes. Kaplan–Meier curves were used to evaluate the prognosis of samples. The correlation between the screened genes and immune cell infiltration was explored using Tumor IMmune Estimation Resource. The GSE70768 dataset from the Gene Expression Omnibus was used to validate the expression of the screened genes.

Results

The ESTIMATE results revealed that high immune, stromal, and ESTIMATE scores and low tumor purity had better prognoses. Function analysis indicated that DEGs are involved in the cytokine–cytokine receptor interaction signaling pathway. In TIME-related DEGs, METTL7B, HOXB8, and TREM1 were closely related to the prognosis. Samples with low expression levels of METTL7B, HOXB8, and TREM1 had better survival times. Similarly, both the validation dataset and qRT-PCR suggested that METTL7B, HOXB8, and TREM1 were significantly decreased. The three genes showed a positive correlation with immune infiltration.

Conclusions

This study identified three TIME-related genes, namely, METTL7B, HOXB8, and TREM1, which correlated with the prognosis of patients with PRAD. Targeting the TIME-related genes might have important clinical implications when making decisions for immunotherapy in PRAD.
Appendix
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Literature
1.
Rebbeck TR. Prostate cancer genetics: variation by race, ethnicity, and geography. Semin Radiat Oncol. 2017;27(1):3–10.PubMedCrossRef
2.
Kumar C, Bagga J, Chiliveru S, Kohli S, Bharadwaj A, Jain M, et al. Substantial remission of prostate adenocarcinoma with dendritic cell therapy APCEDEN(®) in combination with chemotherapy. Future Sci OA. 2019;5(10):Fso435.PubMedPubMedCentralCrossRef
3.
Yunger S, Bar El A, Zeltzer LA, Fridman E, Raviv G, Laufer M, et al. Tumor-infiltrating lymphocytes from human prostate tumors reveal anti-tumor reactivity and potential for adoptive cell therapy. Oncoimmunology. 2019;8(12): e1672494.PubMedPubMedCentralCrossRef
4.
Xu Z, Chen S, Zhang Y, Liu R, Chen M. Roles of m5C RNA modification patterns in biochemical recurrence and tumor microenvironment characterization of prostate adenocarcinoma. Front Immunol. 2022;13: 869759.PubMedPubMedCentralCrossRef
5.
Gu CY, Dai B, Zhu Y, Lin GW, Wang HK, Ye DW, et al. The novel transcriptomic signature of angiogenesis predicts clinical outcome, tumor microenvironment and treatment response for prostate adenocarcinoma. Mol Med. 2022;28(1):78.PubMedPubMedCentralCrossRef
6.
Wang N, Zhu L, Wang L, Shen Z, Huang X. Identification of SHCBP1 as a potential biomarker involving diagnosis, prognosis, and tumor immune microenvironment across multiple cancers. Comput Struct Biotechnol J. 2022;20:3106–19.PubMedPubMedCentralCrossRef
7.
Zhang H, Luo YB, Wu W, Zhang L, Wang Z, Dai Z, et al. The molecular feature of macrophages in Tumor immune microenvironment of glioma patients. Comput Struct Biotechnol J. 2021;19:4603–18.PubMedPubMedCentralCrossRef
8.
Zhong T, Zhang W, Guo H, Pan X, Chen X, He Q, et al. The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies. Acta Pharm Sinica B. 2022;12(4):1761–80.CrossRef
9.
Wu T, Wang W, Shi G, Hao M, Wang Y, Yao M, et al. Targeting HIC1/TGF-β axis-shaped prostate cancer microenvironment restrains its progression. Cell Death Dis. 2022;13(7):624.PubMedPubMedCentralCrossRef
10.
Masetti M, Carriero R, Portale F, Marelli G, Morina N, Pandini M, et al. Lipid-loaded tumor-associated macrophages sustain tumor growth and invasiveness in Prostate cancer. J Exp Med. 2022;219(2):e20210564.PubMedCrossRef
11.
Wang W, Zhang J, Wang Y, Xu Y, Zhang S. Identifies microtubule-binding protein CSPP1 as a novel cancer biomarker associated with ferroptosis and tumor microenvironment. Comput Struct Biotechnol J. 2022;20:3322–35.PubMedPubMedCentralCrossRef
12.
Zhao C, Xiong K, Ji Z, Liu F, Li X. The prognostic value and immunological role of STEAP1 in pan-cancer: a result of data-based analysis. Oxidative Med Cell Longevity. 2022;2022:8297011.
13.
Yang L, Zhang Y, Wang Y, Jiang P, Liu F, Feng N. Ferredoxin 1 is a cuproptosis-key gene responsible for tumor immunity and drug sensitivity: a pan-cancer analysis. Front Pharmacol. 2022;13: 938134.PubMedPubMedCentralCrossRef
14.
Boumahdi S, de Sauvage FJ. The great escape: tumour cell plasticity in resistance to targeted therapy. Nat Rev Drug Discovery. 2020;19(1):39–56.PubMedCrossRef
15.
Ross-Adams H, Lamb AD, Dunning MJ, Halim S, Lindberg J, Massie CM, et al. Integration of copy number and transcriptomics provides risk stratification in prostate cancer: a discovery and validation cohort study. EBio Med. 2015;2(9):1133–44.
16.
17.
Wang P, Wang Y, Hang B, Zou X, Mao JH. A novel gene expression-based prognostic scoring system to predict survival in gastric cancer. Oncotarget. 2016;7(34):55343–51.PubMedPubMedCentralCrossRef
18.
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.PubMedPubMedCentralCrossRef
19.
Wang L, Cao C, Ma Q, Zeng Q, Wang H, Cheng Z, et al. RNA-seq analyses of multiple meristems of soybean: novel and alternative transcripts, evolutionary and functional implications. BMC Plant Biol. 2014;14: 169.PubMedPubMedCentralCrossRef
20.
21.
Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44–57.PubMedCrossRef
22.
Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1–13.PubMedCrossRef
23.
Goeman JJ. L1 penalized estimation in the Cox proportional hazards model. Biometrical J Biometrische Z. 2010;52(1):70–84.CrossRef
24.
Liu XF, Gao ZM, Wang RY, Wang PL, Li K, Gao S. Comparison of Billroth I, Billroth II, and Roux-en-Y reconstructions after distal gastrectomy according to functional recovery: a meta-analysis. Eur Rev Med Pharmacol Sci. 2019;23(17):7532–42.PubMed
25.
Miura K, Ishida K, Fujibuchi W, Ito A, Niikura H, Ogawa H, et al. Differentiating rectal carcinoma by an immunohistological analysis of carcinomas of pelvic organs based on the NCBI Literature Survey and the human protein Atlas database. Surg Today. 2012;42(6):515–25.PubMedCrossRef
26.
Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, et al. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res. 2017;77(21):e108–10.PubMedPubMedCentralCrossRef
27.
Andersen LB, Nørgaard M, Rasmussen M, Fredsøe J, Borre M, Ulhøi BP, et al. Immune cell analyses of the tumor microenvironment in prostate cancer highlight infiltrating regulatory T cells and macrophages as adverse prognostic factors. J Pathol. 2021;255(2):155–65.PubMedCrossRef
28.
29.
Xu M, Li Y, Li W, Zhao Q, Zhang Q, Le K, et al. Immune and stroma related genes in breast cancer: a comprehensive analysis of tumor microenvironment based on the cancer genome atlas (TCGA) database. Front Med. 2020;7: 64.CrossRef
30.
Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51(2):202–6.PubMedPubMedCentralCrossRef
31.
Wu J, Li L, Zhang H, Zhao Y, Zhang H, Wu S, et al. A risk model developed based on tumor microenvironment predicts overall survival and associates with Tumor immunity of patients with lung adenocarcinoma. Oncogene. 2021;40(26):4413–24.PubMedCrossRef
32.
Xiang S, Li J, Shen J, Zhao Y, Wu X, Li M, et al. Identification of prognostic genes in the tumor microenvironment of hepatocellular carcinoma. Front Immunol. 2021;12: 653836.PubMedPubMedCentralCrossRef
33.
Zhang P, An Z, Sun C, Xu Y, Zhang Z. FLG gene mutation up-regulates the abnormal Tumor immune response and promotes the progression of Prostate cancer. Curr Pharm Biotechnol. 2022;23:1658.PubMedCrossRef
34.
Liu Z, Zhong J, Zeng J, Duan X, Lu J, Sun X, et al. Characterization of the m6A-associated tumor immune microenvironment in prostate cancer to aid immunotherapy. Front Immunol. 2021;12: 735170.PubMedPubMedCentralCrossRef
35.
Tao H, Li Z, Mei Y, Li X, Lou H, Dong L, et al. Integrative bioinformatics analysis of a prognostic index and immunotherapeutic targets in renal cell carcinoma. Int Immunopharmacol. 2020;87: 106832.PubMedCrossRef
36.
Zhu D, Wu ZH, Xu L, Yang DL. Single sample scoring of hepatocellular carcinoma: a study based on data mining. Int J ImmunoPathol Pharmacol. 2021;35:20587384211018388.PubMedPubMedCentralCrossRef
37.
Meng J, Guan Y, Wang B, Chen L, Chen J, Zhang M, et al. Risk subtyping and prognostic assessment of prostate cancer based on consensus genes. Commun Biol. 2022;5(1):233.PubMedPubMedCentralCrossRef
38.
Gao L, Meng J, Zhang Y, Gu J, Han Z, Wang X, et al. Development and validation of a six-RNA binding proteins prognostic signature and candidate drugs for prostate cancer. Genomics. 2020;112(6):4980–92.PubMedCrossRef
39.
Meng J, Lu X, Zhou Y, Zhang M, Gao L, Gao S, et al. Characterization of the prognostic values and response to immunotherapy/chemotherapy of Krüppel-like factors in Prostate cancer. J Cell Mol Med. 2020;24(10):5797–810.PubMedPubMedCentralCrossRef
40.
41.
Wang M, Yan J, Cao X, Hua P, Li Z. Hydrogen sulfide modulates epithelial-mesenchymal transition and angiogenesis in non-small cell lung cancer via HIF-1α activation. Biochem Pharmacol. 2020;172: 113775.PubMedCrossRef
42.
Chen X, Li C, Li Y, Wu S, Liu W, Lin T, et al. Characterization of METTL7B to evaluate TME and predict prognosis by integrative analysis of multi-omics data in glioma. Front Mol Biosci. 2021;8: 727481.PubMedPubMedCentralCrossRef
43.
Redecke V, Wu R, Zhou J, Finkelstein D, Chaturvedi V, High AA, et al. Hematopoietic progenitor cell lines with myeloid and lymphoid potential. Nat Methods. 2013;10(8):795–803.PubMedPubMedCentralCrossRef
44.
Zhao Y, Zhang C, Zhu Y, Ding X, Zhou Y, Lv H, et al. TREM1 fosters an immunosuppressive tumor microenvironment in papillary thyroid cancer. Endocr Relat Cancer. 2022;29(2):71–86.PubMedCrossRef
45.
Haque S, Morris JC. Transforming growth factor-β: a therapeutic target for cancer. Hum Vaccines Immunother. 2017;13(8):1741–50.CrossRef
46.
Meng J, Liu Y, Guan S, Fan S, Zhou J, Zhang M, et al. The establishment of immune infiltration based novel recurrence predicting nomogram in prostate cancer. Cancer Med. 2019;8(11):5202–13.PubMedPubMedCentralCrossRef
Metadata
Title
Identifying the tumor immune microenvironment-associated prognostic genes for prostate cancer
Authors
Shi Zong
Ji Gao
Publication date
01-12-2024
Publisher
Springer US
Published in
Discover Oncology / Issue 1/2024
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-023-00856-3

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