Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Identification of Immune Infiltration and Prognostic Biomarkers in Small Cell Lung Cancer Based on Bioinformatic Methods from 3 Studies

Author(s): Jiaoyan Cao and Changhua Yu*

Volume 26, Issue 3, 2023

Published on: 21 July, 2022

Page: [507 - 516] Pages: 10

DOI: 10.2174/1386207325666220408092925

Price: $65

Abstract

Aims: This study aimed to investigate the correlation between gene expression and immune cell infiltration and the overall survival rate in tumor tissues, which may contribute to the therapy and prognosis of small cell lung cancer (SCLC) patients.

Background: SCLC is the most aggressive type of lung neoplasm. There is no proper marker for the treatment and prediction of prognosis in SCLC.

Objectives: Three gene expression profiles of SCLC patients were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified between normal lung samples and SCLC lung samples.

Methods: Functional enrichment analysis of all DEGs was performed to explore the linkage among DEGs, the tumor immune microenvironment, and SCLC tumorigenesis. The common genes among the 3 groups in the Venn diagram and hub genes in protein-protein interaction (PPI) networks were considered potential key genes in SCLC patients. The TIMER (tumor immune estimation resource) database calculation and Kaplan–Meier survival curves were used to investigate the association between potential key genes and immune infiltrate prognosis of SCLC patients.

Results: A total of 750 (top 250 from each study) differentially expressed genes (DEGs) were identified. CLDN18 and BRIP1 were significantly related to immune infiltration in the tumor microenvironment. SHCBP1 and KIF23 were related mostly to prognosis in SCLC patients.

Conclusion: The present study may provide some potential biomarkers for the therapy and prognosis of SCLC.

Keywords: Lung cancer, small cell, immune infiltrate, bioinformatics, biomarkers, prognostic.

« Previous Next »
Graphical Abstract

[1]
Patel, M.I.; Cheng, I.; Gomez, S.L. US lung cancer trends by histologic type. Cancer, 2015, 121(7), 1150-1152.
[http://dx.doi.org/10.1002/cncr.29180] [PMID: 25470142]
[2]
Kim, K.B.; Dunn, C.T.; Park, K.S. Recent progress in mapping the emerging landscape of the small-cell lung cancer genome. Exp. Mol. Med., 2019, 51(12), 1-13.
[http://dx.doi.org/10.1038/s12276-019-0349-5] [PMID: 31827074]
[3]
Byers, L.A.; Rudin, C.M. Small cell lung cancer: Where do we go from here? Cancer, 2015, 121(5), 664-672.
[http://dx.doi.org/10.1002/cncr.29098] [PMID: 25336398]
[4]
Rudin, C.M.; Poirier, J.T.; Byers, L.A.; Dive, C.; Dowlati, A.; George, J.; Heymach, J.V.; Johnson, J.E.; Lehman, J.M.; MacPherson, D.; Massion, P.P.; Minna, J.D.; Oliver, T.G.; Quaranta, V.; Sage, J.; Thomas, R.K.; Vakoc, C.R.; Gazdar, A.F. Molecular subtypes of small cell lung cancer: A synthesis of human and mouse model data. Nat. Rev. Cancer, 2019, 19(5), 289-297.
[http://dx.doi.org/10.1038/s41568-019-0133-9] [PMID: 30926931]
[5]
Yang, J.; Wang, X.; Lu, J.; Chen, H.; Zhao, X.; Gao, C.; Bai, Y.; Zhang, Q.; Fu, X.; Zhang, X. Genomic profiling of circulating tumor DNA from patients with extensive-stage small cell lung cancer identifies potentially actionable alterations. J. Cancer, 2021, 12(17), 5099-5105.
[http://dx.doi.org/10.7150/jca.55134] [PMID: 34335926]
[6]
Peifer, M.; Fernández-Cuesta, L.; Sos, M.L.; George, J.; Seidel, D.; Kasper, L.H.; Plenker, D.; Leenders, F.; Sun, R.; Zander, T.; Menon, R.; Koker, M.; Dahmen, I.; Müller, C.; Di Cerbo, V.; Schildhaus, H.U.; Altmüller, J.; Baessmann, I.; Becker, C.; de Wilde, B.; Vandesompele, J.; Böhm, D.; Ansén, S.; Gabler, F.; Wilkening, I.; Heynck, S.; Heuckmann, J.M.; Lu, X.; Carter, S.L.; Cibulskis, K.; Banerji, S.; Getz, G.; Park, K.S.; Rauh, D.; Grütter, C.; Fischer, M.; Pasqualucci, L.; Wright, G.; Wainer, Z.; Russell, P.; Petersen, I.; Chen, Y.; Stoelben, E.; Ludwig, C.; Schnabel, P.; Hoffmann, H.; Muley, T.; Brockmann, M.; Engel-Riedel, W.; Muscarella, L.A.; Fazio, V.M.; Groen, H.; Timens, W.; Sietsma, H.; Thunnissen, E.; Smit, E.; Heideman, D.A.; Snijders, P.J.; Cappuzzo, F.; Ligorio, C.; Damiani, S.; Field, J.; Solberg, S.; Brustugun, O.T.; Lund-Iversen, M.; Sänger, J.; Clement, J.H.; Soltermann, A.; Moch, H.; Weder, W.; Solomon, B.; Soria, J.C.; Validire, P.; Besse, B.; Brambilla, E.; Brambilla, C.; Lantuejoul, S.; Lorimier, P.; Schneider, P.M.; Hallek, M.; Pao, W.; Meyer-son, M.; Sage, J.; Shendure, J.; Schneider, R.; Büttner, R.; Wolf, J.; Nürnberg, P.; Perner, S.; Heukamp, L.C.; Brindle, P.K.; Haas, S.; Thomas, R.K. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat. Genet., 2012, 44(10), 1104-1110.
[http://dx.doi.org/10.1038/ng.2396] [PMID: 22941188]
[7]
Chan, J.M.; Quintanal-Villalonga, Á.; Gao, V.R.; Xie, Y.; Allaj, V.; Chaudhary, O.; Masilionis, I.; Egger, J.; Chow, A.; Walle, T.; Mattar, M.; Yarlagadda, D.V.K.; Wang, J.L.; Uddin, F.; Offin, M.; Ciampricotti, M.; Qeriqi, B.; Bahr, A.; de Stanchina, E.; Bhanot, U.K.; Lai, W.V.; Bott, M.J.; Jones, D.R.; Ruiz, A.; Baine, M.K.; Li, Y.; Rekhtman, N.; Poirier, J.T.; Nawy, T.; Sen, T.; Mazutis, L.; Hollmann, T.J.; Pe’er, D.; Rudin, C.M. Signatures of plasticity, metastasis, and immunosuppression in an atlas of human small cell lung cancer. Cancer Cell, 2021, 39(11), 1479-1496.e18.
[http://dx.doi.org/10.1016/j.ccell.2021.09.008] [PMID: 34653364]
[8]
Bunn, P.A., Jr; Minna, J.D.; Augustyn, A.; Gazdar, A.F.; Ouadah, Y.; Krasnow, M.A.; Berns, A.; Brambilla, E.; Rekhtman, N.; Massion, P.P.; Niederst, M.; Peifer, M.; Yokota, J.; Govindan, R.; Poirier, J.T.; Byers, L.A.; Wynes, M.W.; McFadden, D.G.; MacPherson, D.; Hann, C.L.; Farago, A.F.; Dive, C.; Teicher, B.A.; Peacock, C.D.; Johnson, J.E.; Cobb, M.H.; Wendel, H.G.; Spigel, D.; Sage, J.; Yang, P.; Pietan-za, M.C.; Krug, L.M.; Heymach, J.; Ujhazy, P.; Zhou, C.; Goto, K.; Dowlati, A.; Christensen, C.L.; Park, K.; Einhorn, L.H.; Edelman, M.J.; Giaccone, G.; Gerber, D.E.; Salgia, R.; Owonikoko, T.; Malik, S.; Karachaliou, N.; Gandara, D.R.; Slotman, B.J.; Blackhall, F.; Goss, G.; Thomas, R.; Rudin, C.M.; Hirsch, F.R. Small cell lung cancer: Can recent advances in biology and molecular biology be translated into improved outcomes. J. Thoracic Oncol., 2016, 11(4), 453-474.
[http://dx.doi.org/10.1016/j.jtho.2016.01.012]
[9]
Horn, L.; Mansfield, A.S.; Szczęsna, A.; Havel, L.; Krzakowski, M.; Hochmair, M.J.; Huemer, F.; Losonczy, G.; Johnson, M.L.; Nishio, M.; Reck, M.; Mok, T.; Lam, S.; Shames, D.S.; Liu, J.; Ding, B.; Lopez-Chavez, A.; Kabbinavar, F.; Lin, W.; Sandler, A.; Liu, S.V. First-Line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N. Engl. J. Med., 2018, 379(23), 2220-2229.
[http://dx.doi.org/10.1056/NEJMoa1809064] [PMID: 30280641]
[10]
Baeuerle, P.A.; Kufer, P.; Bargou, R. BiTE: Teaching antibodies to engage T-cells for cancer therapy. Curr. Opin. Mol. Ther., 2009, 11(1), 22-30.
[PMID: 19169956]
[11]
Poirier, J.T.; George, J.; Owonikoko, T.K.; Berns, A.; Brambilla, E.; Byers, L.A.; Carbone, D.; Chen, H.J.; Christensen, C.L.; Dive, C.; Farago, A.F.; Govindan, R.; Hann, C.; Hellmann, M.D.; Horn, L.; Johnson, J.E.; Ju, Y.S.; Kang, S.; Krasnow, M.; Lee, J.; Lee, S.H.; Leh-man, J.; Lok, B.; Lovly, C.; MacPherson, D.; McFadden, D.; Minna, J.; Oser, M.; Park, K.; Park, K.S.; Pommier, Y.; Quaranta, V.; Ready, N.; Sage, J.; Scagliotti, G.; Sos, M.L.; Sutherland, K.D.; Travis, W.D.; Vakoc, C.R.; Wait, S.J.; Wistuba, I.; Wong, K.K.; Zhang, H.; Daigneault, J.; Wiens, J.; Rudin, C.M.; Oliver, T.G. New approaches to SCLC therapy: From the laboratory to the clinic. J. Thoracic Oncol., 2020, 15(4), 520-540.
[http://dx.doi.org/10.1016/j.jtho.2020.01.016]
[12]
Barrett, T.; Wilhite, S.E.; Ledoux, P.; Evangelista, C.; Kim, I.F.; Tomashevsky, M.; Marshall, K.A.; Phillippy, K.H.; Sherman, P.M.; Holko, M.; Yefanov, A.; Lee, H.; Zhang, N.; Robertson, C.L.; Serova, N.; Davis, S.; Soboleva, A. NCBI GEO: Archive for functional genomics data sets--update. Nucleic Acids Res., 2013, 41(Database issue), D991-D995.
[http://dx.doi.org/10.1093/nar/gks1193] [PMID: 23193258]
[13]
Liao, Y.; Yin, G.; Wang, X.; Zhong, P.; Fan, X.; Huang, C. Identification of candidate genes associated with the pathogenesis of small cell lung cancer via integrated bioinformatics analysis. Oncol. Lett., 2019, 18(4), 3723-3733.
[http://dx.doi.org/10.3892/ol.2019.10685] [PMID: 31516585]
[14]
Wang, S.; He, Z.; Wang, X.; Li, H.; Liu, X.S. Antigen presentation and tumor immunogenicity in cancer immunotherapy response predic-tion. eLife, 2019, 8, 8.
[http://dx.doi.org/10.7554/eLife.49020] [PMID: 31767055]
[15]
Ritchie, M.E.; Phipson, B.; Wu, D.; Hu, Y.; Law, C.W.; Shi, W.; Smyth, G.K. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res., 2015, 43(7), e47.
[http://dx.doi.org/10.1093/nar/gkv007] [PMID: 25605792]
[16]
Liao, Y.; Wang, J.; Jaehnig, E.J.; Shi, Z.; Zhang, B. WebGestalt 2019: Gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Res., 2019, 47(W1), W199-W205.
[http://dx.doi.org/10.1093/nar/gkz401] [PMID: 31114916]
[17]
Szklarczyk, D.; Morris, J.H.; Cook, H.; Kuhn, M.; Wyder, S.; Simonovic, M.; Santos, A.; Doncheva, N.T.; Roth, A.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res., 2017, 45(D1), D362-D368.
[http://dx.doi.org/10.1093/nar/gkw937] [PMID: 27924014]
[18]
Doncheva, N.T.; Morris, J.H.; Gorodkin, J.; Jensen, L.J. Cytoscape stringapp: Network analysis and visualization of proteomics data. J. Proteome Res., 2019, 18(2), 623-632.
[http://dx.doi.org/10.1021/acs.jproteome.8b00702] [PMID: 30450911]
[19]
Li, T.; Fu, J.; Zeng, Z.; Cohen, D.; Li, J.; Chen, Q.; Li, B.; Liu, X.S. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res., 2020, 48(W1), W509-W514.
[http://dx.doi.org/10.1093/nar/gkaa407] [PMID: 32442275]
[20]
Gao, J.; Aksoy, B.A.; Dogrusoz, U.; Dresdner, G.; Gross, B.; Sumer, S.O.; Sun, Y.; Jacobsen, A.; Sinha, R.; Larsson, E.; Cerami, E.; Sand-er, C.; Schultz, N. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal., 2013, 6(269), pl1.
[http://dx.doi.org/10.1126/scisignal.2004088] [PMID: 23550210]
[21]
de Cárcer, G. The mitotic cancer target polo-like kinase 1: Oncogene or tumor suppressor? Genes (Basel), 2019, 10(3), E208.
[http://dx.doi.org/10.3390/genes10030208] [PMID: 30862113]
[22]
Sen, T.; Rodriguez, B.L.; Chen, L.; Corte, C.M.D.; Morikawa, N.; Fujimoto, J.; Cristea, S.; Nguyen, T.; Diao, L.; Li, L.; Fan, Y.; Yang, Y.; Wang, J.; Glisson, B.S.; Wistuba, I.I.; Sage, J.; Heymach, J.V.; Gibbons, D.L.; Byers, L.A. Targeting DNA damage response promotes anti-tumor immunity through STING-Mediated T-cell activation in small cell lung cancer. Cancer Discov., 2019, 9(5), 646-661.
[http://dx.doi.org/10.1158/2159-8290.CD-18-1020] [PMID: 30777870]
[23]
Wan, Y.L.; Dai, H.J.; Liu, W.; Ma, H.T. miR-767-3p inhibits growth and migration of lung adenocarcinoma cells by regulating CLDN18. Oncol. Res., 2018, 26(4), 637-644.
[http://dx.doi.org/10.3727/096504017X15112639918174] [PMID: 29169410]
[24]
Zhou, B.; Flodby, P.; Luo, J.; Castillo, D.R.; Liu, Y.; Yu, F.X.; McConnell, A.; Varghese, B.; Li, G.; Chimge, N.O.; Sunohara, M.; Koss, M.N.; Elatre, W.; Conti, P.; Liebler, J.M.; Yang, C.; Marconett, C.N.; Laird-Offringa, I.A.; Minoo, P.; Guan, K.; Stripp, B.R.; Crandall, E.D.; Borok, Z. Claudin-18-mediated YAP activity regulates lung stem and progenitor cell homeostasis and tumorigenesis. J. Clin. Invest., 2018, 128(3), 970-984.
[http://dx.doi.org/10.1172/JCI90429] [PMID: 29400695]
[25]
Moyer, C.L.; Ivanovich, J.; Gillespie, J.L.; Doberstein, R.; Radke, M.R.; Richardson, M.E.; Kaufmann, S.H.; Swisher, E.M.; Goodfellow, P.J. Rare BRIP1 missense alleles confer risk for ovarian and breast cancer. Cancer Res., 2020, 80(4), 857-867.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-1991] [PMID: 31822495]
[26]
Castillo-Guardiola, V.; Sarabia-Meseguer, M.D.; Marín-Vera, M.; Sánchez-Bermúdez, A.I.; Alonso-Romero, J.L.; Noguera-Velasco, J.A.; Ruiz-Espejo, F. New insights into the performance of multigene panel testing: Two novel nonsense variants in BRIP1 and TP53 in a young woman with breast cancer. Cancer Genet., 2018, 228-229, 1-4.
[http://dx.doi.org/10.1016/j.cancergen.2018.06.002] [PMID: 30553462]
[27]
Wang, F.; Li, Y.; Zhang, Z.; Wang, J.; Wang, J. SHCBP1 regulates apoptosis in lung cancer cells through phosphatase and tensin homolog. Oncol. Lett., 2019, 18(2), 1888-1894.
[http://dx.doi.org/10.3892/ol.2019.10520] [PMID: 31423258]
[28]
Zhang, G.Y.; Ma, Z.J.; Wang, L.; Sun, R.F.; Jiang, X.Y.; Yang, X.J.; Long, B.; Ye, H.L.; Zhang, S.Z.; Yu, Z.Y.; Shi, W.G.; Jiao, Z.Y. The role of shcbp1 in signaling and disease. Curr. Cancer Drug Targets, 2019, 19(11), 854-862.
[http://dx.doi.org/10.2174/1568009619666190620114928] [PMID: 31250756]
[29]
Kato, T.; Wada, H.; Patel, P.; Hu, H.P.; Lee, D.; Ujiie, H.; Hirohashi, K.; Nakajima, T.; Sato, M.; Kaji, M.; Kaga, K.; Matsui, Y.; Tsao, M.S.; Yasufuku, K. Overexpression of KIF23 predicts clinical outcome in primary lung cancer patients. Lung Cancer, 2016, 92, 53-61.
[http://dx.doi.org/10.1016/j.lungcan.2015.11.018] [PMID: 26775597]
[30]
Iltzsche, F.; Simon, K.; Stopp, S.; Pattschull, G.; Francke, S.; Wolter, P.; Hauser, S.; Murphy, D.J.; Garcia, P.; Rosenwald, A.; Gaubatz, S. An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma. Oncogene, 2017, 36(1), 110-121.
[http://dx.doi.org/10.1038/onc.2016.181] [PMID: 27212033]

Rights & Permissions Print Cite
Article Metrics
50
2
© 2024 Bentham Science Publishers | Privacy Policy