Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Exploration of NPC2 as a Potential Biomarker for Immunotherapy Using RNA-seq and Protein Data - A New Hypothesis

Author(s): Wenjing Lu, Dandan Li, Feng Tao, Qian Chen, Shuxin Fan, Yan Ma, Hong Dong, Yiqiao Hu* and Chunyan Yue*

Volume 23, Issue 10, 2023

Published on: 10 May, 2023

Page: [1340 - 1353] Pages: 14

DOI: 10.2174/1871530323666230413112614

Price: $65

Abstract

Introduction: NPC2 is well known as a player for cholesterol transport. However, the biological role of NPC2 in cancer development and therapy is far from clear.

Methods: Here, we explore the potential role of NPC2 in prognosis and immunotherapy across multiple cancer types by integrating RNA-seq data from TCGA and GTEx, protein data from CPTAC, and multiple web analysis databases.

Results: Expression depiction between tumour and normal tissues indicated that NPC2 is overexpressed in the majority of the most common cancer types, including glioblastoma and pancreatic cancer, two cancers mostly difficult to diagnose and treat.

Conclusion: Cancer stemness in glioblastoma is negatively associated with NPC2 level. NPC2 expression is positively correlated with immune cell infiltration and the expression of several immune checkpoints. IDH1 mutation in GBM is negatively correlated with NPC2 level, while a positive correlation has been found between TP53 mutation and NPC2 expression in pancreatic cancer. NPC2 is also correlated with levels of serum biomarkers used for diagnosis of pancreatic cancer.

« Previous
Graphical Abstract

[1]
Klein, A.; Amigo, L.; Retamal, M. J.; Morales, M. G.; Miquel, J. F.; Rigotti, A.; Zanlungo, S. NPC2 is expressed in human and murine liver and secreted into bile: Potential implications for body cholesterol homeostasis. Hepatology, 2006, 43(1), 126-133.
[http://dx.doi.org/10.1002/hep.20985] [PMID: 16374838]
[2]
Torres, S.; Balboa, E.; Zanlungo, S.; Enrich, C.; Garcia-Ruiz, C.; Fernandez-Checa, J.C. Lysosomal and mitochondrial liaisons in niemann-pick disease. Front. Physiol., 2017, 8, 982.
[http://dx.doi.org/10.3389/fphys.2017.00982] [PMID: 29249985]
[3]
Kamata, T.; Jin, H.; Giblett, S.; Patel, B.; Patel, F.; Foster, C.; Pritchard, C. The cholesterol‐binding protein NPC 2 restrains recruitment of stromal macrophage‐lineage cells to early‐stage lung tumours. EMBO Mol. Med., 2015, 7(9), 1119-1137.
[http://dx.doi.org/10.15252/emmm.201404838] [PMID: 26183450]
[4]
Wei, D.; Shen, S.; Lin, K.; Lu, F.; Zheng, P.; Wu, S.; Kang, D. NPC2 as a prognostic biomarker for glioblastoma based on integrated bioinformatics analysis and cytological experiments. Front. Genet., 2021, 12, 611442-611442.
[http://dx.doi.org/10.3389/fgene.2021.611442] [PMID: 33777094]
[5]
Duan, Q.; Zhang, H.; Zheng, J.; Zhang, L. Turning cold into hot: Firing up the tumor microenvironment. Trends Cancer, 2020, 6(7), 605-618.
[http://dx.doi.org/10.1016/j.trecan.2020.02.022] [PMID: 32610070]
[6]
Ma, X.; Bi, E.; Lu, Y.; Su, P.; Huang, C.; Liu, L.; Wang, Q.; Yang, M.; Kalady, M.F.; Qian, J.; Zhang, A.; Gupte, A.A.; Hamilton, D.J.; Zheng, C.; Yi, Q. Cholesterol induces CD8+ T cell exhaustion in the tumor microenvironment. Cell Metab., 2019, 30(1), 143-156.e5.
[http://dx.doi.org/10.1016/j.cmet.2019.04.002] [PMID: 31031094]
[7]
Tang, Z.; Kang, B.; Li, C.; Chen, T.; Zhang, Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res., 2019, 47(W1), W556-W560.
[http://dx.doi.org/10.1093/nar/gkz430] [PMID: 31114875]
[8]
Chandrashekar, D.S.; Bashel, B.; Balasubramanya, S.A.H.; Creighton, C.J.; Ponce-Rodriguez, I.; Chakravarthi, B.V.S.K.; Varambally, S. UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia, 2017, 19(8), 649-658.
[http://dx.doi.org/10.1016/j.neo.2017.05.002] [PMID: 28732212]
[9]
Győrffy, B. Survival analysis across the entire transcriptome identifies biomarkers with the highest prognostic power in breast cancer. Comput. Struct. Biotechnol. J., 2021, 19, 4101-4109.
[http://dx.doi.org/10.1016/j.csbj.2021.07.014] [PMID: 34527184]
[10]
Malta, T.M.; Sokolov, A.; Gentles, A.J.; Burzykowski, T.; Poisson, L.; Weinstein, J.N. Kamińska, B.; Huelsken, J.; Omberg, L.; Gevaert, O.; Colaprico, A.; Czerwińska, P.; Mazurek, S.; Mishra, L.; Heyn, H.; Krasnitz, A.; Godwin, A.K.; Lazar, A.J.; Stuart, J.M.; Hoadley, K.A.; Laird, P.W.; Noushmehr, H.; Wiznerowicz, M.; Caesar-Johnson, S.J.; Demchok, J.A.; Felau, I.; Kasapi, M.; Ferguson, M.L.; Hutter, C.M.; Sofia, H.J.; Tarnuzzer, R.; Wang, Z.; Yang, L.; Zenklusen, J.C.; Zhang, J.J.; Chudamani, S.; Liu, J.; Lolla, L.; Naresh, R.; Pihl, T.; Sun, Q.; Wan, Y.; Wu, Y.; Cho, J.; DeFreitas, T.; Frazer, S.; Gehlenborg, N.; Getz, G.; Heiman, D.I.; Kim, J.; Lawrence, M.S.; Lin, P.; Meier, S.; Noble, M.S.; Saksena, G.; Voet, D.; Zhang, H.; Bernard, B.; Chambwe, N.; Dhankani, V.; Knijnenburg, T.; Kramer, R.; Leinonen, K.; Liu, Y.; Miller, M.; Reynolds, S.; Shmulevich, I.; Thorsson, V.; Zhang, W.; Akbani, R.; Broom, B.M.; Hegde, A.M.; Ju, Z.; Kanchi, R.S.; Korkut, A.; Li, J.; Liang, H.; Ling, S.; Liu, W.; Lu, Y.; Mills, G.B.; Ng, K-S.; Rao, A.; Ryan, M.; Wang, J.; Weinstein, J.N.; Zhang, J.; Abeshouse, A.; Armenia, J.; Chakravarty, D.; Chatila, W.K.; de Bruijn, I.; Gao, J.; Gross, B.E.; Heins, Z.J.; Kundra, R.; La, K.; Ladanyi, M.; Luna, A.; Nissan, M.G.; Ochoa, A.; Phillips, S.M.; Reznik, E.; Sanchez-Vega, F.; Sander, C.; Schultz, N.; Sheridan, R.; Sumer, S.O.; Sun, Y.; Taylor, B.S.; Wang, J.; Zhang, H.; Anur, P.; Peto, M.; Spellman, P.; Benz, C.; Stuart, J.M.; Wong, C.K.; Yau, C.; Hayes, D.N.; Parker, J.S.; Wilkerson, M.D.; Ally, A.; Balasundaram, M.; Bowlby, R.; Brooks, D.; Carlsen, R.; Chuah, E.; Dhalla, N.; Holt, R.; Jones, S.J.M.; Kasaian, K.; Lee, D.; Ma, Y.; Marra, M.A.; Mayo, M.; Moore, R.A.; Mungall, A.J.; Mungall, K.; Robertson, A.G.; Sadeghi, S.; Schein, J.E.; Sipahimalani, P.; Tam, A.; Thiessen, N.; Tse, K.; Wong, T.; Berger, A.C.; Beroukhim, R.; Cherniack, A.D.; Cibulskis, C.; Gabriel, S.B.; Gao, G.F.; Ha, G.; Meyerson, M.; Schumacher, S.E.; Shih, J.; Kucherlapati, M.H.; Kucherlapati, R.S.; Baylin, S.; Cope, L.; Danilova, L.; Bootwalla, M.S.; Lai, P.H.; Maglinte, D.T.; Van Den Berg, D.J.; Weisenberger, D.J.; Auman, J.T.; Balu, S.; Bodenheimer, T.; Fan, C.; Hoadley, K.A.; Hoyle, A.P.; Jefferys, S.R.; Jones, C.D.; Meng, S.; Mieczkowski, P.A.; Mose, L.E.; Perou, A.H.; Perou, C.M.; Roach, J.; Shi, Y.; Simons, J.V.; Skelly, T.; Soloway, M.G.; Tan, D.; Veluvolu, U.; Fan, H.; Hinoue, T.; Laird, P.W.; Shen, H.; Zhou, W.; Bellair, M.; Chang, K.; Covington, K.; Creighton, C.J.; Dinh, H.; Doddapaneni, H.V.; Donehower, L.A.; Drummond, J.; Gibbs, R.A.; Glenn, R.; Hale, W.; Han, Y.; Hu, J.; Korchina, V.; Lee, S.; Lewis, L.; Li, W.; Liu, X.; Morgan, M.; Morton, D.; Muzny, D.; Santibanez, J.; Sheth, M.; Shinbrot, E.; Wang, L.; Wang, M.; Wheeler, D.A.; Xi, L.; Zhao, F.; Hess, J.; Appelbaum, E.L.; Bailey, M.; Cordes, M.G.; Ding, L.; Fronick, C.C.; Fulton, L.A.; Fulton, R.S.; Kandoth, C.; Mardis, E.R.; McLellan, M.D.; Miller, C.A.; Schmidt, H.K.; Wilson, R.K.; Crain, D.; Curley, E.; Gardner, J.; Lau, K.; Mallery, D.; Morris, S.; Paulauskis, J.; Penny, R.; Shelton, C.; Shelton, T.; Sherman, M.; Thompson, E.; Yena, P.; Bowen, J.; Gastier-Foster, J.M.; Gerken, M.; Leraas, K.M.; Lichtenberg, T.M.; Ramirez, N.C.; Wise, L.; Zmuda, E.; Corcoran, N.; Costello, T.; Hovens, C.; Carvalho, A.L.; de Carvalho, A.C.; Fregnani, J.H.; Longatto-Filho, A.; Reis, R.M.; Scapulatempo-Neto, C.; Silveira, H.C.S.; Vidal, D.O.; Burnette, A.; Eschbacher, J.; Hermes, B.; Noss, A.; Singh, R.; Anderson, M.L.; Castro, P.D.; Ittmann, M.; Huntsman, D.; Kohl, B.; Le, X.; Thorp, R.; Andry, C.; Duffy, E.R.; Lyadov, V.; Paklina, O.; Setdikova, G.; Shabunin, A.; Tavobilov, M.; McPherson, C.; Warnick, R.; Berkowitz, R.; Cramer, D.; Feltmate, C.; Horowitz, N.; Kibel, A.; Muto, M.; Raut, C.P.; Malykh, A.; Barnholtz-Sloan, J.S.; Barrett, W.; Devine, K.; Fulop, J.; Ostrom, Q.T.; Shimmel, K.; Wolinsky, Y.; Sloan, A.E.; De Rose, A.; Giuliante, F.; Goodman, M.; Karlan, B.Y.; Hagedorn, C.H.; Eckman, J.; Harr, J.; Myers, J.; Tucker, K.; Zach, L.A.; Deyarmin, B.; Hu, H.; Kvecher, L.; Larson, C.; Mural, R.J.; Somiari, S.; Vicha, A.; Zelinka, T.; Bennett, J.; Iacocca, M.; Rabeno, B.; Swanson, P.; Latour, M.; Lacombe, L.; Têtu, B.; Bergeron, A.; McGraw, M.; Staugaitis, S.M.; Chabot, J.; Hibshoosh, H.; Sepulveda, A.; Su, T.; Wang, T.; Potapova, O.; Voronina, O.; Desjardins, L.; Mariani, O.; Roman-Roman, S.; Sastre, X.; Stern, M-H.; Cheng, F.; Signoretti, S.; Berchuck, A.; Bigner, D.; Lipp, E.; Marks, J.; McCall, S.; McLendon, R.; Secord, A.; Sharp, A.; Behera, M.; Brat, D.J.; Chen, A.; Delman, K.; Force, S.; Khuri, F.; Magliocca, K.; Maithel, S.; Olson, J.J.; Owonikoko, T.; Pickens, A.; Ramalingam, S.; Shin, D.M.; Sica, G.; Van Meir, E.G.; Zhang, H.; Eijckenboom, W.; Gillis, A.; Korpershoek, E.; Looijenga, L.; Oosterhuis, W.; Stoop, H.; van Kessel, K.E.; Zwarthoff, E.C.; Calatozzolo, C.; Cuppini, L.; Cuzzubbo, S.; DiMeco, F.; Finocchiaro, G.; Mattei, L.; Perin, A.; Pollo, B.; Chen, C.; Houck, J.; Lohavanichbutr, P.; Hartmann, A.; Stoehr, C.; Stoehr, R.; Taubert, H.; Wach, S.; Wullich, B.; Kycler, W.; Murawa, D.; Wiznerowicz, M.; Chung, K.; Edenfield, W.J.; Martin, J.; Baudin, E.; Bubley, G.; Bueno, R.; De Rienzo, A.; Richards, W.G.; Kalkanis, S.; Mikkelsen, T.; Noushmehr, H.; Scarpace, L.; Girard, N.; Aymerich, M.; Campo, E.; Giné, E.; Guillermo, A.L.; Van Bang, N.; Hanh, P.T.; Phu, B.D.; Tang, Y.; Colman, H.; Evason, K.; Dottino, P.R.; Martignetti, J.A.; Gabra, H.; Juhl, H.; Akeredolu, T.; Stepa, S.; Hoon, D.; Ahn, K.; Kang, K.J.; Beuschlein, F.; Breggia, A.; Birrer, M.; Bell, D.; Borad, M.; Bryce, A.H.; Castle, E.; Chandan, V.; Cheville, J.; Copland, J.A.; Farnell, M.; Flotte, T.; Giama, N.; Ho, T.; Kendrick, M.; Kocher, J-P.; Kopp, K.; Moser, C.; Nagorney, D.; O’Brien, D.; O’Neill, B.P.; Patel, T.; Petersen, G.; Que, F.; Rivera, M.; Roberts, L.; Smallridge, R.; Smyrk, T.; Stanton, M.; Thompson, R.H.; Torbenson, M.; Yang, J.D.; Zhang, L.; Brimo, F.; Ajani, J.A.; Gonzalez, A.M.A.; Behrens, C.; Bondaruk, J.; Broaddus, R.; Czerniak, B.; Esmaeli, B.; Fujimoto, J.; Gershenwald, J.; Guo, C.; Lazar, A.J.; Logothetis, C.; Meric-Bernstam, F.; Moran, C.; Ramondetta, L.; Rice, D.; Sood, A.; Tamboli, P.; Thompson, T.; Troncoso, P.; Tsao, A.; Wistuba, I.; Carter, C.; Haydu, L.; Hersey, P.; Jakrot, V.; Kakavand, H.; Kefford, R.; Lee, K.; Long, G.; Mann, G.; Quinn, M.; Saw, R.; Scolyer, R.; Shannon, K.; Spillane, A.; Stretch, J.; Synott, M.; Thompson, J.; Wilmott, J.; Al-Ahmadie, H.; Chan, T.A.; Ghossein, R.; Gopalan, A.; Levine, D.A.; Reuter, V.; Singer, S.; Singh, B.; Tien, N.V.; Broudy, T.; Mirsaidi, C.; Nair, P.; Drwiega, P.; Miller, J.; Smith, J.; Zaren, H.; Park, J-W.; Hung, N.P.; Kebebew, E.; Linehan, W.M.; Metwalli, A.R.; Pacak, K.; Pinto, P.A.; Schiffman, M.; Schmidt, L.S.; Vocke, C.D.; Wentzensen, N.; Worrell, R.; Yang, H.; Moncrieff, M.; Goparaju, C.; Melamed, J.; Pass, H.; Botnariuc, N.; Caraman, I.; Cernat, M.; Chemencedji, I.; Clipca, A.; Doruc, S.; Gorincioi, G.; Mura, S.; Pirtac, M.; Stancul, I.; Tcaciuc, D.; Albert, M.; Alexopoulou, I.; Arnaout, A.; Bartlett, J.; Engel, J.; Gilbert, S.; Parfitt, J.; Sekhon, H.; Thomas, G.; Rassl, D.M.; Rintoul, R.C.; Bifulco, C.; Tamakawa, R.; Urba, W.; Hayward, N.; Timmers, H.; Antenucci, A.; Facciolo, F.; Grazi, G.; Marino, M.; Merola, R.; de Krijger, R.; Gimenez-Roqueplo, A-P.; Piché, A.; Chevalier, S.; McKercher, G.; Birsoy, K.; Barnett, G.; Brewer, C.; Farver, C.; Naska, T.; Pennell, N.A.; Raymond, D.; Schilero, C.; Smolenski, K.; Williams, F.; Morrison, C.; Borgia, J.A.; Liptay, M.J.; Pool, M.; Seder, C.W.; Junker, K.; Omberg, L.; Dinkin, M.; Manikhas, G.; Alvaro, D.; Bragazzi, M.C.; Cardinale, V.; Carpino, G.; Gaudio, E.; Chesla, D.; Cottingham, S.; Dubina, M.; Moiseenko, F.; Dhanasekaran, R.; Becker, K-F.; Janssen, K-P.; Slotta-Huspenina, J.; Abdel-Rahman, M.H.; Aziz, D.; Bell, S.; Cebulla, C.M.; Davis, A.; Duell, R.; Elder, J.B.; Hilty, J.; Kumar, B.; Lang, J.; Lehman, N.L.; Mandt, R.; Nguyen, P.; Pilarski, R.; Rai, K.; Schoenfield, L.; Senecal, K.; Wakely, P.; Hansen, P.; Lechan, R.; Powers, J.; Tischler, A.; Grizzle, W.E.; Sexton, K.C.; Kastl, A.; Henderson, J.; Porten, S.; Waldmann, J.; Fassnacht, M.; Asa, S.L.; Schadendorf, D.; Couce, M.; Graefen, M.; Huland, H.; Sauter, G.; Schlomm, T.; Simon, R.; Tennstedt, P.; Olabode, O.; Nelson, M.; Bathe, O.; Carroll, P.R.; Chan, J.M.; Disaia, P.; Glenn, P.; Kelley, R.K.; Landen, C.N.; Phillips, J.; Prados, M.; Simko, J.; Smith-McCune, K.; VandenBerg, S.; Roggin, K.; Fehrenbach, A.; Kendler, A.; Sifri, S.; Steele, R.; Jimeno, A.; Carey, F.; Forgie, I.; Mannelli, M.; Carney, M.; Hernandez, B.; Campos, B.; Herold-Mende, C.; Jungk, C.; Unterberg, A.; von Deimling, A.; Bossler, A.; Galbraith, J.; Jacobus, L.; Knudson, M.; Knutson, T.; Ma, D.; Milhem, M.; Sigmund, R.; Godwin, A.K.; Madan, R.; Rosenthal, H.G.; Adebamowo, C.; Adebamowo, S.N.; Boussioutas, A.; Beer, D.; Giordano, T.; Mes-Masson, A-M.; Saad, F.; Bocklage, T.; Landrum, L.; Mannel, R.; Moore, K.; Moxley, K.; Postier, R.; Walker, J.; Zuna, R.; Feldman, M.; Valdivieso, F.; Dhir, R.; Luketich, J.; Pinero, E.M.M.; Quintero-Aguilo, M.; Carlotti, C.G., Jr; Dos Santos, J.S.; Kemp, R.; Sankarankuty, A.; Tirapelli, D.; Catto, J.; Agnew, K.; Swisher, E.; Creaney, J.; Robinson, B.; Shelley, C.S.; Godwin, E.M.; Kendall, S.; Shipman, C.; Bradford, C.; Carey, T.; Haddad, A.; Moyer, J.; Peterson, L.; Prince, M.; Rozek, L.; Wolf, G.; Bowman, R.; Fong, K.M.; Yang, I.; Korst, R.; Rathmell, W.K.; Fantacone-Campbell, J.L.; Hooke, J.A.; Kovatich, A.J.; Shriver, C.D.; DiPersio, J.; Drake, B.; Govindan, R.; Heath, S.; Ley, T.; Van Tine, B.; Westervelt, P.; Rubin, M.A.; Lee, J.I.; Aredes, N.D.; Mariamidze, A. Machine learning identifies stemness features associated with oncogenic dedifferentiation. Cell, 2018, 173(2), 338-354.e15.
[http://dx.doi.org/10.1016/j.cell.2018.03.034] [PMID: 29625051]
[11]
Bonneville, R.; Krook, M.A.; Kautto, E.A.; Miya, J.; Wing, M.R.; Chen, H.Z.; Reeser, J.W.; Yu, L.; Roychowdhury, S. Landscape of microsatellite instability across 39 cancer types. JCO Precis. Oncol., 2017, 2017(1), 1-15.
[http://dx.doi.org/10.1200/PO.17.00073] [PMID: 29850653]
[12]
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]
[13]
Li, T.; Fan, J.; Wang, B.; Traugh, N.; Chen, Q.; Liu, J.S.; Li, B.; Liu, X.S. TIMER: A web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res., 2017, 77(21), e108-e110.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0307] [PMID: 29092952]
[14]
Luo, G.; Jin, K.; Deng, S.; Cheng, H.; Fan, Z.; Gong, Y.; Qian, Y.; Huang, Q.; Ni, Q.; Liu, C.; Yu, X. Roles of CA19-9 in pancreatic cancer: Biomarker, predictor and promoter. Biochim. Biophys. Acta Rev. Cancer, 2021, 1875(2), 188409.
[http://dx.doi.org/10.1016/j.bbcan.2020.188409] [PMID: 32827580]
[15]
Mizrahi, J.D.; Surana, R.; Valle, J.W.; Shroff, R.T. Pancreatic cancer. Lancet, 2020, 395(10242), 2008-2020.
[http://dx.doi.org/10.1016/S0140-6736(20)30974-0] [PMID: 32593337]
[16]
Plaks, V.; Kong, N.; Werb, Z. The cancer stem cell niche: How essential is the niche in regulating stemness of tumor cells? Cell Stem Cell, 2015, 16(3), 225-238.
[http://dx.doi.org/10.1016/j.stem.2015.02.015] [PMID: 25748930]
[17]
Nangia-Makker, P.; Hogan, V.; Raz, A. Galectin-3 and cancer stemness. Glycobiology, 2018, 28(4), 172-181.
[http://dx.doi.org/10.1093/glycob/cwy001] [PMID: 29315388]
[18]
Romano, S.; Tufano, M.; D’Arrigo, P.; Vigorito, V.; Russo, S.; Romano, M.F. Cell stemness, epithelial-to-mesenchymal transition, and immunoevasion: Intertwined aspects in cancer metastasis. Semin. Cancer Biol., 2020, 60, 181-190.
[http://dx.doi.org/10.1016/j.semcancer.2019.08.015] [PMID: 31422157]
[19]
Baretti, M.; Le, D.T. DNA mismatch repair in cancer. Pharmacol. Ther., 2018, 189, 45-62.
[http://dx.doi.org/10.1016/j.pharmthera.2018.04.004] [PMID: 29669262]
[20]
Chan, T.A.; Yarchoan, M.; Jaffee, E.; Swanton, C.; Quezada, S.A.; 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.
[http://dx.doi.org/10.1093/annonc/mdy495] [PMID: 30395155]
[21]
Marabelle, A.; Fakih, M.; Lopez, J.; Shah, M.; Shapira-Frommer, R.; Nakagawa, K.; Chung, H.C.; Kindler, H.L.; Lopez-Martin, J.A.; Miller, W.H., Jr; Italiano, A.; Kao, S.; Piha-Paul, S.A.; Delord, J.P.; McWilliams, R.R.; Fabrizio, D.A.; Aurora-Garg, D.; Xu, L.; Jin, F.; Norwood, K.; Bang, Y.J. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol., 2020, 21(10), 1353-1365.
[http://dx.doi.org/10.1016/S1470-2045(20)30445-9] [PMID: 32919526]
[22]
DePeaux, K.; Delgoffe, G.M. Metabolic barriers to cancer immunotherapy. Nat. Rev. Immunol., 2021, 21(12), 785-797.
[http://dx.doi.org/10.1038/s41577-021-00541-y] [PMID: 33927375]
[23]
Chabanon, R.M.; Rouanne, M.; Lord, C.J.; Soria, J.C.; Pasero, P.; Postel-Vinay, S. Targeting the DNA damage response in immuno-oncology: Developments and opportunities. Nat. Rev. Cancer, 2021, 21(11), 701-717.
[http://dx.doi.org/10.1038/s41568-021-00386-6] [PMID: 34376827]
[24]
Huang, Y.; Kim, B.Y.S.; Chan, C.K.; Hahn, S.M.; Weissman, I.L.; Jiang, W. Improving immune–vascular crosstalk for cancer immunotherapy. Nat. Rev. Immunol., 2018, 18(3), 195-203.
[http://dx.doi.org/10.1038/nri.2017.145] [PMID: 29332937]
[25]
Morad, G.; Helmink, B.A.; Sharma, P.; Wargo, J.A. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade. Cell, 2021, 184(21), 5309-5337.
[http://dx.doi.org/10.1016/j.cell.2021.09.020] [PMID: 34624224]
[26]
Kleeff, J.; Korc, M.; Apte, M.; La Vecchia, C.; Johnson, C.D.; Biankin, A.V.; Neale, R.E.; Tempero, M.; Tuveson, D.A.; Hruban, R.H.; Neoptolemos, J.P. Pancreatic cancer. Nat. Rev. Dis. Primers, 2016, 2(1), 16022.
[http://dx.doi.org/10.1038/nrdp.2016.22] [PMID: 27158978]
[27]
Xu, Y.; Zhang, Q.; Tan, L.; Xie, X.; Zhao, Y. The characteristics and biological significance of NPC2: Mutation and disease. Mutat. Res. Rev. Mutat. Res., 2019, 782, 108284.
[http://dx.doi.org/10.1016/j.mrrev.2019.108284] [PMID: 31843136]
[28]
Kotiyal, S.; Bhattacharya, S. Breast cancer stem cells, EMT and therapeutic targets. Biochem. Biophys. Res. Commun., 2014, 453(1), 112-116.
[http://dx.doi.org/10.1016/j.bbrc.2014.09.069] [PMID: 25261721]
[29]
Rajayi, H.; Tavasolian, P.; Rezalotfi, A.; Ebrahimi, M. Cancer stem cells targeting; The Lessons from the interaction of the immune system, the cancer stem cells and the tumor niche. Int. Rev. Immunol., 2019, 38(6), 267-283.
[http://dx.doi.org/10.1080/08830185.2019.1669593] [PMID: 31578892]
[30]
Yang, L.; Shi, P.; Zhao, G.; Xu, J.; Peng, W.; Zhang, J.; Zhang, G.; Wang, X.; Dong, Z.; Chen, F.; Cui, H. Targeting cancer stem cell pathways for cancer therapy. Signal Transduct. Target. Ther., 2020, 5(1), 8.
[http://dx.doi.org/10.1038/s41392-020-0110-5] [PMID: 32296030]
[31]
Yamanashi, Y.; Takada, T.; Yoshikado, T.; Shoda, J.I.; Suzuki, H. NPC2 regulates biliary cholesterol secretion via stimulation of ABCG5/G8-mediated cholesterol transport. Gastroenterology, 2011, 140(5), 1664-1674.
[http://dx.doi.org/10.1053/j.gastro.2011.01.050] [PMID: 21315718]
[32]
Abi-Mosleh, L.; Infante, R.E.; Radhakrishnan, A.; Goldstein, J.L.; Brown, M.S. Cyclodextrin overcomes deficient lysosome-to-endoplasmic reticulum transport of cholesterol in Niemann-Pick type C cells. Proc. Natl. Acad. Sci., 2009, 106(46), 19316-19321.
[http://dx.doi.org/10.1073/pnas.0910916106] [PMID: 19884502]
[33]
Jun, S.Y.; Brown, A.J.; Chua, N.K.; Yoon, J.Y.; Lee, J.J.; Yang, J.O.K.; Jang, I.; Jeon, S.J.; Choi, T.I.K.; Kim, C.H.; Kim, N.S. Reduction of squalene epoxidase by cholesterol accumulation accelerates colorectal cancer progression and metastasis. Gastroenterology, 2021, 160(4), 1194-1207.e28.
[http://dx.doi.org/10.1053/j.gastro.2020.09.009] [PMID: 32946903]
[34]
Zhang, H.; Zhao, W.; Li, X.; He, Y. Cholesterol metabolism as a potential therapeutic target and a prognostic biomarker for cancer immunotherapy. OncoTargets Ther., 2021, 14, 3803-3812.
[http://dx.doi.org/10.2147/OTT.S315998] [PMID: 34188488]
[35]
Liao, Y.J.; Fang, C.C.; Yen, C.H.; Hsu, S.M.; Wang, C.K.; Huang, S.F.; Liang, Y.C.; Lin, Y.Y.; Chu, Y.T.; Arthur Chen, Y.M. Niemann-Pick type C2 protein regulates liver cancer progression via modulating ERK1/2 pathway: Clinicopathological correlations and therapeutical implications. Int. J. Cancer, 2015, 137(6), 1341-1351.
[http://dx.doi.org/10.1002/ijc.29507] [PMID: 25754535]
[36]
Kalbasi, A.; Ribas, A. Tumour-intrinsic resistance to immune checkpoint blockade. Nat. Rev. Immunol., 2020, 20(1), 25-39.
[http://dx.doi.org/10.1038/s41577-019-0218-4] [PMID: 31570880]
[37]
Kennedy, L.B.; Salama, A.K.S. A review of cancer immunotherapy toxicity. CA Cancer J. Clin., 2020, 70(2), 86-104.
[http://dx.doi.org/10.3322/caac.21596] [PMID: 31944278]
[38]
Cristescu, R.; Mogg, R.; Ayers, M.; Albright, A.; Murphy, E.; Yearley, J.; Sher, X.; Liu, X.Q.; Lu, H.; Nebozhyn, M.; Zhang, C.; Lunceford, J.K.; Joe, A.; Cheng, J.; Webber, A.L.; Ibrahim, N.; Plimack, E.R.; Ott, P.A.; Seiwert, T.Y.; Ribas, A.; McClanahan, T.K.; Tomassini, J.E.; Loboda, A.; Kaufman, D. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy. Science, 2018, 362(6411), eaar3593.
[http://dx.doi.org/10.1126/science.aar3593] [PMID: 30309915]
[39]
Ganesh, K.; Stadler, Z.K.; Cercek, A.; Mendelsohn, R.B.; Shia, J.; Segal, N.H.; Diaz, L.A., Jr Immunotherapy in colorectal cancer: Rationale, challenges and potential. Nat. Rev. Gastroenterol. Hepatol., 2019, 16(6), 361-375.
[http://dx.doi.org/10.1038/s41575-019-0126-x] [PMID: 30886395]
[40]
Luchini, C.; Bibeau, F.; Ligtenberg, M.J.L.; Singh, N.; Nottegar, A.; Bosse, T.; Miller, R.; Riaz, N.; Douillard, J.Y.; Andre, F.; Scarpa, A. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann. Oncol., 2019, 30(8), 1232-1243.
[http://dx.doi.org/10.1093/annonc/mdz116] [PMID: 31056702]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy