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Combinatorial Chemistry & High Throughput Screening

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

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Research Article

PHD3 as a Prognosis Marker and its Relationship with Immune Infiltration in Lung Adenocarcinoma

Author(s): Lei Wang, Yingying Zhong, Guiping Wang, Huan An, Qiang Gao and Yun Ye*

Volume 25, Issue 13, 2022

Published on: 17 May, 2022

Page: [2255 - 2263] Pages: 9

DOI: 10.2174/1386207325666220128122640

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Abstract

Background: Lung adenocarcinoma (LUAD) is a highly heterogeneous malignant tumor. Therefore, it is necessary to find predictive biomarkers related to the prognosis and immune infiltration of lung adenocarcinoma, which may provide an effective theoretical basis for its clinical treatment.

Objective: This study aimed to evaluate whether the expression level of PHD3 in lung adenocarcinoma (LUAD) is related to immunity.

Methods: PHD3 expression was analyzed by the ONCOMINE, TIMER, UALCAN, and GEPIA databases. The correlations between clinical information and PHD3 expression were analyzed by the LinkedOmics database. Then, we evaluated the influence of PHD3 on the survival of LUAD patients using Kaplan-Meier Plotter and HPA database. We explored the correlation between PHD3 and tumor immunity using TIMER and the correlation module of TISDIB. Finally, we used the cBioportal database to analyze PHD3 mutations in LUAD.

Results: Comprehensive analysis displayed PHD3 expression to be clearly higher in LUAD compared to adjacent normal tissues. PHD3 expression was identified to be positively associated with tumor purity, histological type, and later pathological stage. Survival curve results revealed the high expression of PHD3 in LUAD patients to be accompanied by a poor prognosis. Further study indicated PHD3 to be significantly related to a variety of tumor immune cells and molecules. Moreover, among the LUAD cases with gene alteration of PHD3, amplification was the most common of all alteration types.

Conclusion: PHD3 may be used as a biomarker for survival and immunotherapy of LUAD.

Keywords: Lung adenocarcinoma, PHD3, bioinformatics, immunotherapy, biomarker, prognosis.

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[1]
Beer, D.G.; Kardia, S.L.R.; Huang, C-C.; Giordano, T.J.; Levin, A.M.; Misek, D.E.; Lin, L.; Chen, G.; Gharib, T.G.; Thomas, D.G.; Lizy-ness, M.L.; Kuick, R.; Hayasaka, S.; Taylor, J.M.; Iannettoni, M.D.; Orringer, M.B.; Hanash, S. Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat. Med., 2002, 8(8), 816-824.
[http://dx.doi.org/10.1038/nm733] [PMID: 12118244]
[2]
Garon, E.B.; Rizvi, N.A.; Hui, R.; Leighl, N.; Balmanoukian, A.S.; Eder, J.P.; Patnaik, A.; Aggarwal, C.; Gubens, M.; Horn, L.; Carcereny, E.; Ahn, M.J.; Felip, E.; Lee, J.S.; Hellmann, M.D.; Hamid, O.; Goldman, J.W.; Soria, J.C.; Dolled-Filhart, M.; Rutledge, R.Z.; Zhang, J.; Lunceford, J.K.; Rangwala, R.; Lubiniecki, G.M.; Roach, C.; Emancipator, K.; Gandhi, L. Pembrolizumab for the treatment of non-small-cell lung cancer. N. Engl. J. Med., 2015, 372(21), 2018-2028.
[http://dx.doi.org/10.1056/NEJMoa1501824] [PMID: 25891174]
[3]
Rizvi, N.A.; Mazières, J.; Planchard, D.; Stinchcombe, T.E.; Dy, G.K.; Antonia, S.J.; Horn, L.; Lena, H.; Minenza, E.; Mennecier, B.; Otter-son, G.A.; Campos, L.T.; Gandara, D.R.; Levy, B.P.; Nair, S.G.; Zalcman, G.; Wolf, J.; Souquet, P.J.; Baldini, E.; Cappuzzo, F.; Chouaid, C.; Dowlati, A.; Sanborn, R.; Lopez-Chavez, A.; Grohe, C.; Huber, R.M.; Harbison, C.T.; Baudelet, C.; Lestini, B.J.; Ramalingam, S.S. Ac-tivity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol., 2015, 16(3), 257-265.
[http://dx.doi.org/10.1016/S1470-2045(15)70054-9] [PMID: 25704439]
[4]
Fehrenbacher, L.; Spira, A.; Ballinger, M.; Kowanetz, M.; Vansteenkiste, J.; Mazieres, J.; Park, K.; Smith, D.; Artal-Cortes, A.; Lewanski, C.; Braiteh, F.; Waterkamp, D.; He, P.; Zou, W.; Chen, D.S.; Yi, J.; Sandler, A.; Rittmeyer, A. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet, 2016, 387(10030), 1837-1846.
[http://dx.doi.org/10.1016/S0140-6736(16)00587-0] [PMID: 26970723]
[5]
Zhu, J.; Liu, Y.; Ao, H.; Liu, M.; Zhao, M.; Ma, J. Comprehensive analysis of the immune implication of ACK1 gene in non-small cell lung cancer. Front. Oncol., 2020, 10, 1132.
[http://dx.doi.org/10.3389/fonc.2020.01132] [PMID: 32793482]
[6]
Uehara, M.; Sano, K.; Ikeda, H.; Nonaka, M.; Asahina, I. Hypoxia-inducible factor 1 alpha in oral squamous cell carcinoma and its rela-tion to prognosis. Oral Oncol., 2009, 45(3), 241-246.
[http://dx.doi.org/10.1016/j.oraloncology.2008.05.007] [PMID: 18675581]
[7]
Puppala, S.; Patel, R.; Yap, K.S.; Patel, J.; Wah, T.; Snoddon, A. Hepatocellular carcinoma: modern image-guided therapies. Postgrad. Med. J., 2016, 92(1085), 165-171.
[http://dx.doi.org/10.1136/postgradmedj-2014-132923] [PMID: 26787919]
[8]
Sugano, K.; Tack, J.; Kuipers, E.J.; Graham, D.Y.; El-Omar, E.M.; Miura, S.; Haruma, K.; Asaka, M.; Uemura, N.; Malfertheiner, P. Kyoto global consensus report on Helicobacter pylori gastritis. Gut, 2015, 64(9), 1353-1367.
[http://dx.doi.org/10.1136/gutjnl-2015-309252] [PMID: 26187502]
[9]
Schofield, C.J.; Ratcliffe, P.J. Oxygen sensing by HIF hydroxylases. Nat. Rev. Mol. Cell Biol., 2004, 5(5), 343-354.
[http://dx.doi.org/10.1038/nrm1366] [PMID: 15122348]
[10]
Xia, X.; Wang, S.; Ni, B. Hypoxic gastric cancer-derived exosomes promote progression and metastasis via MiR-301a-3p/PHD3/HIF- 1α positive feedback loop. 2020, 39(39), 6231-6244.
[http://dx.doi.org/10.1038/s41388-020-01425-6]
[11]
Erez, N.; Milyavsky, M.; Eilam, R.; Shats, I.; Goldfinger, N.; Rotter, V. Expression of prolyl-hydroxylase-1 (PHD1/EGLN2) suppresses hypoxia inducible factor-1alpha activation and inhibits tumor growth. Cancer Res., 2003, 63(24), 8777-8783.
[http://dx.doi.org/10.1002/cncr.11858] [PMID: 14695194]
[12]
Rantanen, K.; Pursiheimo, J.; Högel, H.; Himanen, V.; Metzen, E.; Jaakkola, P.M. Prolyl hydroxylase PHD3 activates oxygen-dependent protein aggregation. Mol. Biol. Cell, 2008, 19(5), 2231-2240.
[http://dx.doi.org/10.1091/mbc.e07-11-1124] [PMID: 18337469]
[13]
Dopeso, H.; Jiao, H.K.; Cuesta, A.M.; Henze, A.T.; Jurida, L.; Kracht, M.; Acker-Palmer, A.; Garvalov, B.K.; Acker, T. PHD3 controls lung cancer metastasis and resistance to EGFR inhibitors through TGFα. Cancer Res., 2018, 78(7), 1805-1819.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-1346] [PMID: 29339541]
[14]
Vasaikar, S.V.; Straub, P.; Wang, J.; Zhang, B. LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res., 2018, 46(D1), D956-D963.
[http://dx.doi.org/10.1093/nar/gkx1090] [PMID: 29136207]
[15]
Osaki, Y.; Nishikawa, H. Treatment for hepatocellular carcinoma in Japan over the last three decades: Our experience and published work review. Hepatol. Res., 2015, 45(1), 59-74.
[http://dx.doi.org/10.1111/hepr.12378]
[16]
Miikkulainen, P.; Högel, H.; Rantanen, K.; Suomi, T.; Kouvonen, P.; Elo, L.L.; Jaakkola, P.M. HIF prolyl hydroxylase PHD3 regulates translational machinery and glucose metabolism in clear cell renal cell carcinoma. Cancer Metab., 2017, 5(1), 5-5.
[http://dx.doi.org/10.1186/s40170-017-0167-y] [PMID: 28680592]
[17]
Chen, S.; Zhang, J.; Li, X.; Luo, X.; Fang, J.; Chen, H. The expression of prolyl hydroxylase domain enzymes are up-regulated and nega-tively correlated with Bcl-2 in non-small cell lung cancer. Mol. Cell. Biochem., 2011, 358(1-2), 257-263.
[http://dx.doi.org/10.1007/s11010-011-0976-1] [PMID: 21748337]
[18]
Andersen, S.; Donnem, T.; Stenvold, H.; Al-Saad, S.; Al-Shibli, K.; Busund, L.T.; Bremnes, R.M. Overexpression of the HIF hydroxylas-es PHD1, PHD2, PHD3 and FIH are individually and collectively unfavorable prognosticators for NSCLC survival. PLoS One, 2011, 6(8), e23847.
[http://dx.doi.org/10.1371/journal.pone.0023847] [PMID: 21887331]
[19]
Giatromanolaki, A.; Koukourakis, M.I.; Pezzella, F.; Turley, H.; Sivridis, E.; Bouros, D.; Bougioukas, G.; Harris, A.L.; Gatter, K.C. Ex-pression of prolyl-hydroxylases PHD-1, 2 and 3 and of the asparagine hydroxylase FIH in non-small cell lung cancer relates to an activat-ed HIF pathway. Cancer Lett., 2008, 262(1), 87-93.
[http://dx.doi.org/10.1016/j.canlet.2007.11.041] [PMID: 18187257]
[20]
Rittmeyer, A.; Barlesi, F.; Waterkamp, D.; Park, K.; Ciardiello, F.; von Pawel, J.; Gadgeel, S.M.; Hida, T.; Kowalski, D.M.; Dols, M.C.; Cortinovis, D.L.; Leach, J.; Polikoff, J.; Barrios, C.; Kabbinavar, F.; Frontera, O.A.; De Marinis, F.; Turna, H.; Lee, J.S.; Ballinger, M.; Kowanetz, M.; He, P.; Chen, D.S.; Sandler, A.; Gandara, D.R. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet, 2017, 389(10066), 255-265.
[http://dx.doi.org/10.1016/S0140-6736(16)32517-X] [PMID: 27979383]
[21]
Killock, D. Lung Cancer: Frontline nivolumab - CheckMate 026 ends in stalemate. Nat. Rev. Clin. Oncol., 2017, 14(8), 458-459.
[http://dx.doi.org/10.1038/nrclinonc.2017.102] [PMID: 28726813]
[22]
Singal, G.; Miller, P.G.; Agarwala, V.; Li, G.; Kaushik, G.; Backenroth, D.; Gossai, A.; Frampton, G.M.; Torres, A.Z.; Lehnert, E.M.; Bourque, D.; O’Connell, C.; Bowser, B.; Caron, T.; Baydur, E.; Seidl-Rathkopf, K.; Ivanov, I.; Alpha-Cobb, G.; Guria, A.; He, J.; Frank, S.; Nunnally, A.C.; Bailey, M.; Jaskiw, A.; Feuchtbaum, D.; Nussbaum, N.; Abernethy, A.P.; Miller, V.A. Association of patient character-istics and tumor genomics with clinical outcomes among patients with non-small cell lung cancer using a clinicogenomic database. JAMA, 2019, 321(14), 1391-1399.
[http://dx.doi.org/10.1001/jama.2019.3241] [PMID: 30964529]
[23]
Yoshioka, H.; Katakami, N.; Okamoto, H.; Iwamoto, Y.; Seto, T.; Takahashi, T.; Sunaga, N.; Kudoh, S.; Chikamori, K.; Harada, M.; Tanaka, H.; Saito, H.; Saka, H.; Takeda, K.; Nogami, N.; Masuda, N.; Harada, T.; Kitagawa, H.; Horio, H.; Yamanaka, T.; Fukuoka, M.; Yamamoto, N.; Nakagawa, K. A randomized, open-label, phase III trial comparing amrubicin versus docetaxel in patients with previously treated non-small-cell lung cancer. Ann. Oncol., 2017, 28(2), 285-291.
[http://dx.doi.org/10.1093/annonc/mdw621] [PMID: 28426104]
[24]
Paz-Ares, L.; Luft, A.; Vicente, D.; Tafreshi, A.; Gümüş, M.; Mazières, J.; Hermes, B.; Çay Şenler, F.; Csőszi, T.; Fülöp, A.; Rodríguez-Cid, J.; Wilson, J.; Sugawara, S.; Kato, T.; Lee, K.H.; Cheng, Y.; Novello, S.; Halmos, B.; Li, X.; Lubiniecki, G.M.; Piperdi, B.; Kowalski, D.M. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N. Engl. J. Med., 2018, 379(21), 2040-2051.
[http://dx.doi.org/10.1056/NEJMoa1810865] [PMID: 30280635]
[25]
Herbst, R.S.; Giaccone, G.; de Marinis, F.; Reinmuth, N.; Vergnenegre, A.; Barrios, C.H.; Morise, M.; Felip, E.; Andric, Z.; Geater, S.; Özgüroğlu, M.; Zou, W.; Sandler, A.; Enquist, I.; Komatsubara, K.; Deng, Y.; Kuriki, H.; Wen, X.; McCleland, M.; Mocci, S.; Jassem, J.; Spigel, D.R. Atezolizumab for first-line treatment of PD-l1-selected patients with NSCLC. N. Engl. J. Med., 2020, 383(14), 1328-1339.
[http://dx.doi.org/10.1056/NEJMoa1917346] [PMID: 32997907]
[26]
Laughney, A.M.; Hu, J.; Campbell, N.R.; Bakhoum, S.F.; Setty, M.; Lavallée, V.P.; Xie, Y.; Masilionis, I.; Carr, A.J.; Kottapalli, S.; Allaj, V.; Mattar, M.; Rekhtman, N.; Xavier, J.B.; Mazutis, L.; Poirier, J.T.; Rudin, C.M.; Pe’er, D.; Massagué, J. Regenerative lineages and im-mune-mediated pruning in lung cancer metastasis. Nat. Med., 2020, 26(2), 259-269.
[http://dx.doi.org/10.1038/s41591-019-0750-6] [PMID: 32042191]
[27]
Arjunan, A.; Pajaniradje, S.; Francis, A.P.; Subramanian, S.; Chandramohan, S.; Parthasarathi, D.; Sajith, A.M.; Padusha, M.S.A.; Mathur, P.P.; Rajagopalan, R. Epigenetic modulation and apoptotic induction by a novel imidazo-benzamide derivative in human lung adenocarci-noma cells. Daru, 2021, 29(2), 377-387.
[http://dx.doi.org/10.1007/s40199-021-00419-3] [PMID: 34642906]

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