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BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Research

Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients

Authors: Qianhe Ren, Qifan Li, Chenye Shao, Pengpeng Zhang, Zhuangzhuang Hu, Jun Li, Wei Wang, Yue Yu

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

Lung adenocarcinoma (LUAD) is an extraordinarily malignant tumor, with rapidly increasing morbidity and poor prognosis. Immunotherapy has emerged as a hopeful therapeutic modality for lung adenocarcinoma. Furthermore, a prognostic model (based on immune genes) can fulfill the purpose of early diagnosis and accurate prognostic prediction.

Methods

Immune-related mRNAs (IRmRNAs) were utilized to construct a prognostic model that sorted patients into high- and low-risk groups. Then, the prediction efficacy of our model was evaluated using a nomogram. The differences in overall survival (OS), the tumor mutation landscape, and the tumor microenvironment were further explored between different risk groups. In addition, the immune genes comprising the prognostic model were subjected to single-cell RNA sequencing to investigate the expression of these immune genes in different cells. Finally, the functions of BIRC5 were validated through in vitro experiments.

Results

Patients in different risk groups exhibited sharply significant variations in OS, pathway activity, immune cell infiltration, mutation patterns, and immune response. Single-cell RNA sequencing revealed that the expression level of BIRC5 was significantly high in T cells. Cell experiments further revealed that BIRC5 knockdown markedly reduced LUAD cell proliferation.

Conclusion

This model can function as an instrumental variable in the prognostic, molecular, and therapeutic prediction of LUAD, shedding new light on the optimal clinical practice guidelines for LUAD patients.
Appendix
Available only for authorised users
Literature
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMedCrossRef
2.
Zhao H, Wu L, Yan G, Chen Y, Zhou M, Wu Y, Li Y. Inflammation and tumor progression: signaling pathways and targeted intervention. Signal Transduct Target Ther. 2021;6(1):263.PubMedPubMedCentralCrossRef
3.
Travis WD, Garg K, Franklin WA, Wistuba II, Sabloff B, Noguchi M, Kakinuma R, Zakowski M, Ginsberg M, Padera R, Jacobson F, Johnson BE, Hirsch F, Brambilla E, Flieder DB, Geisinger KR, Thunnisen F, Kerr K, Yankelevitz D, Franks TJ, Galvin JR, Henderson DW, Nicholson AG, Hasleton PS, Roggli V, Tsao MS, Cappuzzo F, Vazquez M. Evolving concepts in the pathology and computed tomography imaging of lung adenocarcinoma and bronchioloalveolar carcinoma. J Clin Oncol. 2005;23(14):3279–87.PubMedCrossRef
4.
Ren J, Zhang H, Wang J, Xu Y, Zhao L, Yuan Q. Transcriptome analysis of adipocytokines and their-related LncRNAs in lung adenocarcinoma revealing the association with prognosis, immune infiltration, and metabolic characteristics. Adipocyte. 2022;11(1):250–65.PubMedPubMedCentralCrossRef
5.
Cai W, Lin D, Wu C, Li X, Zhao C, Zheng L, Chuai S, Fei K, Zhou C, Hirsch FR. Intratumoral Heterogeneity of ALK-Rearranged and ALK/EGFR Coaltered Lung Adenocarcinoma. J Clin Oncol. 2015;33(32):3701–9.PubMedPubMedCentralCrossRef
6.
Ambrogio C., Kohler J., Zhou Z. W, Wang H., Paranal R., Li J., Capelletti M., Caffarra C., Li S., Lv Q., Gondi S., Hunter J. C., Lu J., Chiarle R., Santamaria D., Westover K. D., Janne P. A. KRAS Dimerization Impacts MEK Inhibitor Sensitivity and Oncogenic Activity of Mutant KRAS. Cell. 2018;172(4):857–868 e15.PubMedCrossRef
7.
Foggetti G, Li C, Cai H, Hellyer JA, Lin WY, Ayeni D, Hastings K, Choi J, Wurtz A, Andrejka L, Maghini DG, Rashleigh N, Levy S, Homer R, Gettinger SN, Diehn M, Wakelee HA, Petrov DA, Winslow MM, Politi K. Genetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In Vivo. Cancer Discov. 2021;11(7):1736–53.PubMedPubMedCentralCrossRef
8.
Perez-Ramirez C, Canadas-Garre M, Molina MA, Faus-Dader MJ, Calleja-Hernandez MA. MET/HGF targeted drugs as potential therapeutic strategies in non-small cell lung cancer. Pharmacol Res. 2015;102:90–106.PubMedCrossRef
9.
Manchado E., Weissmueller S., Morris J. P. t., Chen C. C., Wullenkord R., Lujambio A., de Stanchina E., Poirier J. T., Gainor J. F., Corcoran R. B., Engelman J. A., Rudin C. M., Rosen N.,  Lowe S. W., A combinatorial strategy for treating KRAS-mutant lung cancer. Nature 2016, 534 (7609):647–51.
10.
Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12(2):175–80.PubMedCrossRef
11.
Scagliotti GV, Bironzo P, Vansteenkiste JF. Addressing the unmet need in lung cancer: The potential of immuno-oncology. Cancer Treat Rev. 2015;41(6):465–75.PubMedCrossRef
12.
Kang J, Zhang C, Zhong WZ. Neoadjuvant immunotherapy for non-small cell lung cancer: State of the art. Cancer Commun (Lond). 2021;41(4):287–302.PubMedCrossRef
13.
Zhou F, Qiao M, Zhou C. The cutting-edge progress of immune-checkpoint blockade in lung cancer. Cell Mol Immunol. 2021;18(2):279–93.PubMedCrossRef
14.
Forde PM, Chaft JE, Pardoll DM. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018;379(9): e14.PubMedCrossRef
15.
Yi M, Zheng X, Niu M, Zhu S, Ge H, Wu K. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions. Mol Cancer. 2022;21(1):28.PubMedPubMedCentralCrossRef
16.
Huang C, Li M, Liu B, Zhu H, Dai Q, Fan X, Mehta K, Huang C, Neupane P, Wang F, Sun W, Umar S, Zhong C, Zhang J. Relating Gut microbiome and its modulating factors to immunotherapy in solid tumors: a systematic review. Front Oncol. 2021;11: 642110.PubMedPubMedCentralCrossRef
17.
Passaro A, Brahmer J, Antonia S, Mok T, Peters S. Managing resistance to immune checkpoint inhibitors in lung cancer: treatment and novel strategies. J Clin Oncol. 2022;40(6):598–610.PubMedCrossRef
18.
Li W, Hao Y, Zhang X, Xu S, Pang D. Targeting RNA N(6)-methyladenosine modification: a precise weapon in overcoming tumor immune escape. Mol Cancer. 2022;21(1):176.PubMedPubMedCentralCrossRef
19.
Xiao Y, Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther. 2021;221: 107753.PubMedCrossRef
20.
Chen Y, Chen S, Lei E. DiffChIPL: a differential peak analysis method for high-throughput sequencing data with biological replicates based on limma. Bioinformatics (Oxford, England). 2022;38(17):4062–9.PubMed
21.
Zhang P, Pei S, Gong Z, Feng Y, Zhang X, Yang F, Wang W. By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinoma. Front Immunol. 2023;14:1115272.PubMedPubMedCentralCrossRef
22.
Chen X, Yuan Q, Liu J, Xia S, Shi X, Su Y, Wang Z, Li S, Shang D. in vivoComprehensive characterization of extracellular matrix-related genes in PAAD identified a novel prognostic panel related to clinical outcomes and immune microenvironment: a silico analysis with and vitro validation. Front Immunol. 2022;13: 985911.PubMedPubMedCentralCrossRef
23.
24.
Pei S, Zhang P, Yang L, Kang Y, Chen H, Zhao S, Dai Y, Zheng M, Xia Y, Xie H. Exploring the role of sphingolipid-related genes in clinical outcomes of breast cancer. Front Immunol. 2023;14:1116839.PubMedPubMedCentralCrossRef
25.
Yuan Q, Ren J, Wang Z, Ji L, Deng D, Shang D. Identification of the real hub gene and construction of a novel prognostic signature for pancreatic adenocarcinoma based on the weighted gene co-expression network analysis and least absolute shrinkage and selection operator algorithms. Front Genet. 2021;12: 692953.PubMedPubMedCentralCrossRef
26.
27.
28.
29.
Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023;51(D1):D587–92.PubMedCrossRef
30.
Singh A, Horng H, Roshkovan L, Weeks JK, Hershman M, Noel P, Luna JM, Cohen EA, Pantalone L, Shinohara RT, Bauml JM, Thompson JC, Aggarwal C, Carpenter EL, Katz SI, Kontos D. Development of a robust radiomic biomarker of progression-free survival in advanced non-small cell lung cancer patients treated with first-line immunotherapy. Sci Rep. 2022;12(1):9993.PubMedPubMedCentralCrossRef
31.
Chen SJ, Wang SC, Chen YC. The Immunotherapy for Colorectal Cancer, Lung Cancer and Pancreatic Cancer. Int J Mol Sci 2021, 22 (23).
32.
Fukumura D, Kloepper J, Amoozgar Z, Duda DG, Jain RK. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol. 2018;15(5):325–40.PubMedPubMedCentralCrossRef
33.
Bejarano L, Jordao MJC, Joyce JA. Therapeutic targeting of the tumor microenvironment. Cancer Discov. 2021;11(4):933–59.PubMedCrossRef
34.
Sun L., Kees T., Almeida A. S., Liu, B., He X. Y., Ng D., Han X., Spector D. L., McNeish I. A., Gimotty P., Adams S., Egeblad M., Activating a collaborative innate-adaptive immune response to control metastasis. Cancer Cell 2021, 39 (10), 1361–1374 e9.
35.
Sawant DV, Yano H, Chikina M, Zhang Q, Liao M, Liu C, Callahan DJ, Sun Z, Sun T, Tabib T, Pennathur A, Corry DB, Luketich JD, Lafyatis R, Chen W, Poholek AC, Bruno TC, Workman CJ, Vignali DAA. Adaptive plasticity of IL-10(+) and IL-35(+) T(reg) cells cooperatively promotes tumor T cell exhaustion. Nat Immunol. 2019;20(6):724–35.PubMedPubMedCentralCrossRef
36.
Venkatesan S., Angelova M., Puttick C., Zhai H., Caswell D. R., Lu W. T., Dietzen M., Galanos P., Evangelou K., Bellelli R., Lim E. L., Watkins T. B. K., Rowan A., Teixeira V. H., Zhao Y., Chen H., Ngo B., Zalmas L. P., Al Bakir M., Hobor S., Gronroos E., Pennycuick A., Nigro E., Campbell B. B., Brown W. L, Akarca A. U., Marafioti T., Wu M. Y., Howell M.,  Boulton S. J., Bertoli C., Fenton T. R., de Bruin R. A. M., Maya-Mendoza A.,   Santoni-Rugiu E., Hynds R. E., Gorgoulis V. G., Jamal-Hanjani M., McGranahan N., Harris R. S., Janes S. M., Bartkova J., Bakhoum S. F., Bartek J., Kanu N., Swanton C., Consortium T. R., Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution. Cancer Discov 2021;11(10):2456-2473.
37.
Kagoya Y, Tanaka S, Guo T, Anczurowski M, Wang CH, Saso K, Butler MO, Minden MD, Hirano N. A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects. Nat Med. 2018;24(3):352–9.PubMedPubMedCentralCrossRef
38.
Espinosa-Cotton M, Rodman Iii SN, Ross KA, Jensen IJ, Sangodeyi-Miller K, McLaren AJ, Dahl RA, Gibson-Corley KN, Koch AT, Fu YX, Badovinac VP, Laux D, Narasimhan B, Simons AL. Interleukin-1 alpha increases anti-tumor efficacy of cetuximab in head and neck squamous cell carcinoma. J Immunother Cancer. 2019;7(1):79.PubMedPubMedCentralCrossRef
39.
40.
41.
42.
Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, Porta-Pardo E, Gao GF, Plaisier CL, Eddy JA, Ziv E, Culhane AC, Paull EO, Sivakumar IKA, Gentles AJ, Malhotra R, Farshidfar F, Colaprico A, Parker JS, Mose LE, Vo NS, Liu J, Liu Y, Rader J, Dhankani V, Reynolds SM, Bowlby R, Califano A, Cherniack AD, Anastassiou D, Bedognetti D, Mokrab Y, Newman AM, Rao A, Chen K, Krasnitz A, Hu H, Malta TM, Noushmehr H, Pedamallu CS, Bullman S, Ojesina AI, Lamb A, Zhou W, Shen H, Choueiri TK, Weinstein JN, Guinney J, Saltz J, Holt RA, Rabkin CS, Cancer Genome Atlas Research N, Lazar AJ, Serody JS, Demicco EG, Disis ML, Vincent BG, Shmulevich I. The Immune Landscape of Cancer. Immunity 2018, 48 (4), 812–830 e14.
43.
Gajewski TF, Meng Y, Harlin H. Immune suppression in the tumor microenvironment. J Immunother. 2006;29(3):233–40.PubMedCrossRef
44.
Zuo S, Wei M, Wang S, Dong J, Wei J. Pan-Cancer Analysis of Immune Cell Infiltration Identifies a Prognostic Immune-Cell Characteristic Score (ICCS) in Lung Adenocarcinoma. Front Immunol. 2020;11:1218.PubMedPubMedCentralCrossRef
45.
Kennedy R, Celis E. Multiple roles for CD4+ T cells in anti-tumor immune responses. Immunol Rev. 2008;222:129–44.PubMedCrossRef
46.
47.
Probst HC, McCoy K, Okazaki T, Honjo T, van den Broek M. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat Immunol. 2005;6(3):280–6.PubMedCrossRef
48.
Braun DA, Street K, Burke K. P, Cookmeyer D.L, Denize T, Pedersen C. B, Gohil S. H, Schindler N, Pomerance L, Hirsch L, Bakouny Z, Hou Y, Forman J, Huang T, Li S, Cui A, Keskin D. B, Steinharter J, Bouchard G, Sun M, Pimenta E. M, Xu W, Mahoney K. M, McGregor B. A, Hirsch M. S, Chang S. L, Livak K. J, McDermott D. F, Shukla S. A, Olsen L. R, Signoretti S, Sharpe A. H, Irizarry R. A, Choueiri T. K, Wu C. J. Progressive immune dysfunction with advancing disease stage in renal cell carcinoma. Cancer Cell 2021;39(5):632–648 e8.
49.
Chyuan IT, Chu CL, Hsu PN. Targeting the Tumor Microenvironment for Improving Therapeutic Effectiveness in Cancer Immunotherapy: Focusing on Immune Checkpoint Inhibitors and Combination Therapies. Cancers (Basel) 2021, 13 (6).
50.
Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: Co-inhibitory receptors with specialized functions in immune regulation. Immunity. 2016;44(5):989–1004.PubMedPubMedCentralCrossRef
51.
Wang Q, Zhang J, Tu H, Liang D, Chang DW, Ye Y, Wu X. Soluble immune checkpoint-related proteins as predictors of tumor recurrence, survival, and T cell phenotypes in clear cell renal cell carcinoma patients. J Immunother Cancer. 2019;7(1):334.PubMedPubMedCentralCrossRef
52.
53.
54.
Edner NM, Carlesso G, Rush JS, Walker LSK. Targeting co-stimulatory molecules in autoimmune disease. Nat Rev Drug Discov. 2020;19(12):860–83.PubMedCrossRef
55.
Chen Y, Li ZY, Zhou GQ, Sun Y. An immune-related gene prognostic index for head and neck squamous cell carcinoma. Clin Cancer Res. 2021;27(1):330–41.PubMedCrossRef
56.
Jiang P, Gu S, Pan D, Fu J, Sahu A, Hu X, Li Z, Traugh N, Bu X, Li B, Liu J, Freeman GJ, Brown MA, Wucherpfennig KW, Liu XS. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nat Med. 2018;24(10):1550–8.PubMedPubMedCentralCrossRef
57.
Chan TA, Yarchoan M, Jaffee E, Swanton C, Quezada SA, Stenzinger A, Peters S. Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic. Ann Oncol. 2019;30(1):44–56.PubMedCrossRef
58.
Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O’Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093–104.PubMedPubMedCentralCrossRef
59.
Sun H, Liu SY, Zhou JY, Xu JT, Zhang HK, Yan HH, Huan JJ, Dai PP, Xu CR, Su J, Guan YF, Yi X, Yu RS, Zhong WZ, Wu YL. Specific TP53 subtype as biomarker for immune checkpoint inhibitors in lung adenocarcinoma. EBioMedicine. 2020;60: 102990.PubMedPubMedCentralCrossRef
60.
Xu J. Y, Zhang C, Wang X, Zhai L, Ma  Y, Mao Y, Qian K, Sun C, Liu Z, Jiang S, Wang M, Feng  L, Zhao L, Liu P, Wang B, Zhao X, Xie H, Yang X, Zhao L, Chang Y, Jia J, Wang X, Zhang Y, Wang Y, Yang Y, Wu Z, Yang L, Liu B, Zhao T, Ren S, Sun A, Zhao Y, Ying W, Wang F, Wang G, Zhang Y, Cheng S, Qin J, Qian X, Wang Y, Li J, He F, Xiao T, Tan M. Integrative Proteomic Characterization of Human Lung Adenocarcinoma. Cell 2020. 182(1)245–261 e17.
61.
Schoenfeld AJ, Rizvi H, Bandlamudi C, Sauter JL, Travis WD, Rekhtman N, Plodkowski AJ, Perez-Johnston R, Sawan P, Beras A, Egger JV, Ladanyi M, Arbour KC, Rudin CM, Riely GJ, Taylor BS, Donoghue MTA, Hellmann MD. Clinical and molecular correlates of PD-L1 expression in patients with lung adenocarcinomas. Ann Oncol. 2020;31(5):599–608.PubMedCrossRef
62.
Wagner J, Rapsomaniki MA, Chevrier S, Anzeneder T, Langwieder C, Dykgers A, Rees M, Ramaswamy, A, Muenst S, Soysal SD, Jacobs A, Windhager J, Silina K, van den Broek M, Dedes KJ, Rodriguez Martinez M, Weber WP, Bodenmiller BA. Single-Cell Atlas of the Tumor and Immune Ecosystem of Human Breast Cancer. Cell 2019, 177 (5), 1330–1345 e18.
63.
Wang Y, Li X, Wang H, Zhang G. CircCAMSAP1 promotes non-small cell lung cancer proliferation and inhibits cell apoptosis by sponging miR-1182 and regulating BIRC5. Bioengineered. 2022;13(2):2428–39.PubMedPubMedCentralCrossRef
64.
Han F, Yang S, Wang W, Huang X, Huang D, Chen S. Retraction Notice to: Silencing of lncRNA LINC00857 Enhances BIRC5-Dependent Radio-Sensitivity of Lung Adenocarcinoma Cells by Recruiting NF-kappaB1. Mol Ther Nucleic Acids. 2022;28:538.PubMedPubMedCentralCrossRef
65.
Li F, Aljahdali I, Ling X. Cancer therapeutics using survivin BIRC5 as a target: what can we do after over two decades of study? J Exp Clin Cancer Res. 2019;38(1):368.PubMedPubMedCentralCrossRef
66.
67.
68.
Chen S, Han F, Huang D, Meng J, Chu J, Wang M, Wang P. Fe(3)O(4) magnetic nanoparticle-enhanced radiotherapy for lung adenocarcinoma via delivery of siBIRC5 and AS-ODN. J Transl Med. 2021;19(1):337.PubMedPubMedCentralCrossRef
Metadata
Title
Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients
Authors
Qianhe Ren
Qifan Li
Chenye Shao
Pengpeng Zhang
Zhuangzhuang Hu
Jun Li
Wei Wang
Yue Yu
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11249-8

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