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Journal of Cancer Research and Clinical Oncology

Erschienen in:

21.07.2023 | Research

A novel tumor microenvironment-related gene signature with immune features for prognosis of lung squamous cell carcinoma

verfasst von: Wan Jia Han, Pengzhi He

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 14/2023

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Abstract

Purpose

Lung squamous cell carcinoma (LUSC) is an aggressive subset of non-small-cell lung cancer (NSCLC). The tumor microenvironment (TME) plays an important role in the development of LUSC. We aim to identify potential therapeutic targets and a TME-related prognostic signature and for LUSC.

Methods

TME-related genes were obtained from TCGA-LUSC dataset. LUSC samples were clustered by the non-negative matrix clustering algorithm (NMF). The prognostic signature was constructed through univariate Cox regression, multivariate Cox regression, and the least absolute shrinkage and selection operator (LASSO) analyses. Gene set enrichment analysis (GSEA) was carried out to explore the enrichment pathways.

Results

This study constructed a prognostic signature which contained 12 genes: HHIPL2, PLK4, SLC6A4, LSM1, TSLP, P4HA1, AMH, CLDN5, NRTN, CDH2, PTGIS, and STX1A. Patients were classified into high-risk and low-risk groups according to the median risk score of this signature. Compared with low-risk group patients, patients in high-risk group patients had poorer overall survival, which demonstrated this signature was an independent prognostic factor. Besides, correlation analysis and GSEA results revealed that genes of this signature were correlated with immune cells and drug response.

Conclusion

Our novel signature based on 12 TME-related genes might be applied as an independent prognostic indicator. Importantly, the signature could be a promising biomarker and accurately predict the prognosis of LUSC patients.

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Akizuki R, Shimobaba S, Matsunaga T, Endo S, Ikari A (2017) Claudin-5, -7, and -18 suppress proliferation mediated by inhibition of phosphorylation of Akt in human lung squamous cell carcinoma. Biochim Biophys Acta Mol Cell Res 1864(2):293–302PubMed

Barr FA, Silljé HH, Nigg EA (2004) Polo-like kinases and the orchestration of cell division. Nat Rev Mol Cell Biol 5(6):429–440PubMed

Barta JA, Powell CA, Wisnivesky JP (2019) Global epidemiology of lung cancer. Ann Glob Health 85(1):8PubMedPubMedCentral

Becht E, Giraldo NA, Lacroix L, Buttard B, Elarouci N, Petitprez F et al (2016) Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol 17(1):218PubMedPubMedCentral

Beck TN, Korobeynikov VA, Kudinov AE, Georgopoulos R, Solanki NR, Andrews-Hoke M et al (2016) Anti-Müllerian hormone signaling regulates epithelial plasticity and chemoresistance in lung cancer. Cell Rep 16(3):657–671PubMedPubMedCentral

Blanche P, Dartigues JF, Jacqmin-Gadda H (2013) Estimating and comparing time-dependent areas under receiver-operating characteristic curves for censored event times with competing risks. Stat Med 32(30):5381–5397PubMed

Caetano MS, Hassane M, Van HT, Bugarin E, Cumpian AM, McDowell CL, Cavazos CG, Zhang H, Deng S, Diao L, Wang J, Evans SE, Behrens C, Wistuba II, Fuqua SAW, Lin H, Stabile LP, Watowich SS, Kadara H, Moghaddam SJ (2018) Sex specific function of epithelial STAT3 signaling in pathogenesis of K-ras mutant lung cancer. Nat Commun 9(1):4589PubMedPubMedCentral

Cao ZQ, Wang Z, Leng P (2019) Aberrant N-cadherin expression in cancer. Biomed Pharmacother 118:109320PubMed

Chen C, Cheng X, Li S, Chen H, Cui M, Bian L, Jin H (2021) A novel signature for predicting prognosis of smoking-related squamous cell carcinoma. Front Genet 12:666371PubMedPubMedCentral

Ding L, Lu Z, Lu Q, Chen YH (2013) The claudin family of proteins in human malignancy: a clinical perspective. Cancer Manag Res 5:367–375PubMedPubMedCentral

Domagala-Kulawik J, Osinska I, Hoser G (2014) Mechanisms of immune response regulation in lung cancer. Transl Lung Cancer Res 3(1):15–22PubMedPubMedCentral

Ferrer L, GiajLevra M, Brevet M, Antoine M, Mazieres J, Rossi G, Chiari R, Westeel V, Poudenx M, Letreut J, Gervais R, Osman G, Girard N, Toffart AC, Novello S, Moro-Sibilot D (2019) A brief report of transformation from NSCLC to SCLC: molecular and therapeutic characteristics. J Thorac Oncol 14(1):130–134PubMed

Garcia-Gomez A, Rodríguez-Ubreva J, Ballestar E (2018) Epigenetic interplay between immune, stromal and cancer cells in the tumor microenvironment. Clin Immunol 196:64–71PubMed

Gaujoux R, Seoighe C (2010) A flexible R package for nonnegative matrix factorization. BMC Bioinformatics 11:367PubMedPubMedCentral

Gocheva V, Naba A, Bhutkar A, Guardia T, Miller KM, Li CM, Dayton TL, Sanchez-Rivera FJ, Kim-Kiselak C, Jailkhani N, Winslow MM, Del Rosario A, Hynes RO, Jacks T (2017) Quantitative proteomics identify Tenascin-C as a promoter of lung cancer progression and contributor to a signature prognostic of patient survival. Proc Natl Acad Sci U S A 114(28):E5625–E5634PubMedPubMedCentral

Guvakova MA, Prabakaran I, Wu Z, Hoffman DI, Huang Y, Tchou J et al (2020) CDH2/N-cadherin and early diagnosis of invasion in patients with ductal carcinoma in situ. Breast Cancer Res Treat 183(2):333–346PubMed

Hamada T, Cao Y, Qian ZR, Masugi Y, Nowak JA, Yang J et al (2017) Aspirin use and colorectal cancer survival according to tumor CD274 (programmed cell death 1 ligand 1) expression status. J Clin Oncol 35(16):1836–1844PubMedPubMedCentral

Hattar K, Reinert CP, Sibelius U, Gökyildirim MY, Subtil FSB, Wilhelm J et al (2017) Lipoteichoic acids from Staphylococcus aureus stimulate proliferation of human non-small-cell lung cancer cells in vitro. Cancer Immunol Immunother 66(6):799–809PubMedPubMedCentral

Hinshaw DC, Shevde LA (2019) The tumor microenvironment innately modulates cancer progression. Cancer Res 79(18):4557–4566PubMedPubMedCentral

Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA, Mariotto AB, Lowy DR, Feuer EJ (2020) The effect of advances in lung-cancer treatment on population mortality. N Engl J Med 383(7):640–649PubMedPubMedCentral

Hui L, Chen Y (2015) Tumor microenvironment: sanctuary of the devil. Cancer Lett 368(1):7–13PubMed

Hui L, Zhang S, Dong X, Tian D, Cui Z, Qiu X (2013) Prognostic significance of twist and N-cadherin expression in NSCLC. PLoS ONE 8(4):e62171PubMedPubMedCentral

Katoh Y, Katoh M (2006) Comparative genomics on HHIP family orthologs. Int J Mol Med 17(2):391–395PubMed

Kocher F, Tymoszuk P, Amann A, Sprung S, Salcher S, Daum S et al (2021) Deregulated glutamate to pro-collagen conversion is associated with adverse outcome in lung cancer and may be targeted by renin-angiotensin-aldosterone system (RAS) inhibition. Lung Cancer 159:84–95PubMed

Kostetskii I, Li J, Xiong Y, Zhou R, Ferrari VA, Patel VV et al (2005) Induced deletion of the N-cadherin gene in the heart leads to dissolution of the intercalated disc structure. Circ Res 96(3):346–354PubMed

Lau SK, Boutros PC, Pintilie M, Blackhall FH, Zhu CQ, Strumpf D et al (2007) Three-gene prognostic classifier for early-stage non small-cell lung cancer. J Clin Oncol 25(35):5562–5569PubMed

Li H, Zhao H, Yu J, Su Y, Cao S, An X et al (2011) Increased prevalence of regulatory T cells in the lung cancer microenvironment: a role of thymic stromal lymphopoietin. Cancer Immunol Immunother 60(11):1587–1596PubMed

Li M, Wu F, Zheng Q, Wu Y, Wu Y (2020a) Identification of potential diagnostic and prognostic values of P4HA1 expression in lung cancer, breast cancer, and head and neck cancer. DNA Cell Biol 39(5):909–917PubMed

Li R, Liu X, Zhou XJ, Chen X, Li JP, Yin YH et al (2020b) Identification and validation of the prognostic value of immune-related genes in non-small cell lung cancer. Am J Transl Res 12(9):5844–5865PubMedPubMedCentral

Li W, Li X, Gao LN, You CG (2020c) Integrated analysis of the functions and prognostic values of RNA binding proteins in lung squamous cell carcinoma. Front Genet 11:185PubMedPubMedCentral

Li Z, Wang Y, Shen Y, Qian C, Oupicky D, Sun M (2020d) Targeting pulmonary tumor microenvironment with CXCR4-inhibiting nanocomplex to enhance anti-PD-L1 immunotherapy. Sci Adv 6(20):9240

Liu H, Liu B, Zheng F, Chen X, Ye L, He Y (2020a) Distribution of pathogenic bacteria in lower respiratory tract infection in lung cancer patients after chemotherapy and analysis of integron resistance genes in respiratory tract isolates of uninfected patients. J Thorac Dis 12(8):4216–4223PubMedPubMedCentral

Liu Z, Wan Y, Qiu Y, Qi X, Yang M, Huang J, Zhang Q (2020b) Development and validation of a novel immune-related prognostic model in lung squamous cell carcinoma. Int J Med Sci 17(10):1393–1405PubMedPubMedCentral

Liu H, Liu B, Zhang L, Li M, Chen C, He S, Luo T, He X, Tan L (2021) An investigation to identify tumor microenvironment-related genes of prognostic value in lung squamous cell carcinoma based on The Cancer Genome Atlas. Transl Cancer Res 10(4):1885–1899PubMedPubMedCentral

Ma C, Luo H, Cao J, Zheng X, Zhang J, Zhang Y, Fu Z (2020) Identification of a novel tumor microenvironment-associated eight-gene signature for prognosis prediction in lung adenocarcinoma. Front Mol Biosci 7:571641PubMedPubMedCentral

Nakashima T, Huang C, Liu D, Kameyama K, Masuya D, Kobayashi S et al (2003) Neural-cadherin expression associated with angiogenesis in non-small-cell lung cancer patients. Br J Cancer 88(11):1727–1733PubMedPubMedCentral

Parzen JS, Almahariq MF, Quinn TJ, Siddiqui ZA, Thompson AB, Guerrero T, Lee K, Stevens C, Grills IS (2021) Higher biologically effective dose is associated with improved survival in patients with squamous cell carcinoma of the lung treated with stereotactic body radiation therapy. Radiother Oncol 160:25–31PubMed

Paschoud S, Bongiovanni M, Pache JC, Citi S (2007) Claudin-1 and claudin-5 expression patterns differentiate lung squamous cell carcinomas from adenocarcinomas. Mod Pathol 20(9):947–954PubMed

Pitt JM, Marabelle A, Eggermont A, Soria JC, Kroemer G, Zitvogel L (2016) Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy. Ann Oncol 27(8):1482–1492PubMed

Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19(11):1423–1437PubMedPubMedCentral

Reinhold WC, Sunshine M, Liu H, Varma S, Kohn KW, Morris J et al (2012) Cell Miner: a web-based suite of genomic and pharmacologic tools to explore transcript and drug patterns in the NCI-60 cell line set. Cancer Res 72(14):3499–3511PubMedPubMedCentral

Ritchie ME, Phipson B, Wu D, Hu Y, Law CW et al (2015) limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43(7):e47PubMedPubMedCentral

Russick J, Joubert PE, Gillard-Bocquet M, Torset C, Meylan M, Petitprez F et al (2020) Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions. J Immunother Cancer 8(2):e001054PubMedPubMedCentral

Sasaki Y, Ochiai T, Takamura M, Kondo Y, Yokoyama C, Hara S (2017) Role of prostacyclin synthase in carcinogenesis. Prostagland Other Lipid Mediat 133:49–52

Sava G, Perissin L, Zorzet S, Piccini P, Giraldi T (1989) Antimetastatic action of the prostacyclin analog iloprost in the mouse. Clin Exp Metastasis 7(6):671–678PubMed

Schröder MS, Culhane AC, Quackenbush J, Haibe-Kains B (2011) survcomp: an R/Bioconductor package for performance assessment and comparison of survival models. Bioinformatics 27(22):3206–3208PubMedPubMedCentral

Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30PubMed

Simon N, Friedman J, Hastie T, Tibshirani R (2011) Regularization paths for Cox’s proportional hazards model via coordinate descent. J Stat Softw 39(5):1–13PubMedPubMedCentral

Stearman RS, Dwyer-Nield L, Zerbe L, Blaine SA, Chan Z et al (2005) Analysis of orthologous gene expression between human pulmonary adenocarcinoma and a carcinogen-induced murine model. Am J Pathol 167:1763–1775PubMedPubMedCentral

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102(43):15545–15550PubMedPubMedCentral

Sugai M, Yanagawa N, Shikanai S, Hashimoto M, Saikawa H, Osakabe M et al (2022) Correlation of tumor microenvironment-related markers with clinical outcomes in patients with squamous cell carcinoma of the lung. Transl Lung Cancer Res 11(6):975–990PubMedPubMedCentral

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209–249PubMed

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z (2017) GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res 45(W1):W98–W102PubMedPubMedCentral

Tibshirani R (1997) The lasso method for variable selection in the Cox model. Stat Med 16(4):385–395PubMed

Topalian SL, Taube JM, Anders RA, Pardoll DM (2016) Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer 16(5):275–287PubMedPubMedCentral

Tu Y, Yao S, Chen Q, Li W, Song Y, Zhang P (2022) 5-Hydroxytryptamine activates a 5-HT/c-Myc/SLC6A4 signaling loop in non-small cell lung cancer. Biochim Biophys Acta Gen Subj 1866(4):130093PubMed

Udo EE, Al-Sweih N, John P, Chugh TD (2002) Antibiotic resistance of enterococci isolated at a teaching hospital in Kuwait. Diagn Microbiol Infect Dis 43(3):233–238PubMed

Uhlén M, Fagerberg L, Hallström BM et al (2015) Proteomics. Tissue-based map of the human proteome. Science 347:1260419PubMed

Vickers AJ, Elkin EB (2006) Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making 26(6):565–574PubMedPubMedCentral

Wang Z, Wang Z, Niu X, Liu J, Wang Z, Chen L, Qin B (2019) Identification of seven-gene signature for prediction of lung squamous cell carcinoma. Onco Targets Ther 12:5979–5988PubMedPubMedCentral

Wu T, Dai Y (2017) Tumor microenvironment and therapeutic response. Cancer Lett 387:61–68PubMed

Xiao Y, Yu D (2021) Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther 221:107753PubMed

Youlden DR, Cramb SM, Baade PD (2008) The International Epidemiology of Lung Cancer: geographical distribution and secular trends. J Thorac Oncol 3(8):819–831PubMed

Yu G, Wang LG, Han Y, He QY (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16(5):284–287PubMedPubMedCentral

Zhang M, Di Martino JS, Bowman RL, Campbell NR, Baksh SC, Simon-Vermot T et al (2018) Adipocyte-derived lipids mediate melanoma progression via FATP proteins. Cancer Discov 8(8):1006–1025PubMedPubMedCentral

Zhang X, Shi X, Zhao H, Jia X, Yang Y (2021) Identification and validation of a tumor microenvironment-related gene signature for prognostic prediction in advanced-stage non-small-cell lung cancer. Biomed Res Int 2021:8864436PubMedPubMedCentral

Zheng Y, Bi G, Bian Y, Li M, Huang Y, Zhao M, Chen Z, Zhan C, Jiang W (2021) The tumor environment immune phenotype of LUSC by genome-wide analysis. Int Immunopharmacol 96:107564PubMed

Zhou Q, Fan G, Dong Y (2020) Polo-like kinase 4 correlates with greater tumor size, lymph node metastasis and confers poor survival in non-small cell lung cancer. J Clin Lab Anal 34(4):e23152PubMed

Zhu XL, Han X, Xin XF, Song HJ, Guo H (2020) Correlations of analgesic dosage of morphine with SLC6A4 gene polymorphisms in patients with lung cancer. Eur Rev Med Pharmacol Sci 24(9):5046–5052PubMed

Titel: A novel tumor microenvironment-related gene signature with immune features for prognosis of lung squamous cell carcinoma
verfasst von: Wan Jia Han
Pengzhi He
Publikationsdatum: 21.07.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 14/2023
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-023-05042-0

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A novel tumor microenvironment-related gene signature with immune features for prognosis of lung squamous cell carcinoma

Abstract

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Methods

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Conclusion

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