Integrated Analysis of Cancer Tissue and Vitreous Humor from Retinoblastoma Eyes Reveals Unique Tumor-Specific Metabolic and Cellular Pathways in Advanced and Non-Advanced Tumors
Abstract
:1. Introduction
2. Materials and Methods
2.1. Clinical Samples
2.2. Tumor mRNA Profiling
2.3. Metabolomics
2.4. Multi-Omic Data Analysis
2.5. Pathway Enrichment Analysis and Regulatory Network Analysis
2.6. Gene Expression Analysis
2.7. Cell Lines
2.8. Histopathology & Light Microscopy
2.9. Immunohistochemistry
2.10. Lentiviral Plasmid and Vector
2.11. Western Blotting
2.12. Statistical Analysis
3. Results
3.1. Transcriptomic Profiling of Retinoblastoma Tumors Identifies Distinct Expression Profiles in Rb Subtypes
3.2. Rb Tumor Clinical Subtypes Demonstrate Altered Molecular Pathways Unique to Their Stage
3.3. Quantitative Validation of Microarray-Identified Targets Confirm Distinct Transcriptomic Profiles in Rb Subtypes
3.4. Differentially Accumulated Metabolites Reveal the Enrichment of Key Metabolic Pathways in Rb Vitreous Humor
3.5. Integrated Transcriptomic and Metabolome Analysis Reveals Gene–Metabolite Interaction Networks Associated with Retinoblastoma
3.6. Validation of Molecular Signatures That Specify Clinical and Histopathological Grades of Retinoblastoma
3.7. Validation of Multi-Omics Findings in Rb Subjects and the In Vitro Model
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Lohmann, D.R.; Gallie, B.L. GeneReviews®; Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Grip, K.W., Mirzaa, G.M., Amemiya, A., Eds.; University of Washington: Seattle, WA, USA, 1993. [Google Scholar]
- Dimaras, H.; Corson, T.W.; Cobrinik, D.; White, A.; Zhao, J.; Munier, F.L.; Abramson, D.L.; Shields, C.L.; Chantada, G.L.; Njuguna, F.; et al. Retinoblastoma. Nat. Rev. Dis. Prim. 2015, 1, 15021. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, X.L.; Singh, H.P.; Wang, L.; Qi, D.L.; Poulos, B.K.; Abramson, D.H.; Jhanwar, S.C.; Cobrinik, D. Rb suppresses human cone-precursor-derived retinoblastoma tumours. Nature 2014, 514, 385–388. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, J.; Benavente, C.A.; McEvoy, J.; Flores-Otero, J.; Ding, L.; Chen, X.; Ulyanov, A.; Wu, G.; Wilson, M.; Wang, J.; et al. A novel retinoblastoma therapy from genomic and epigenetic analyses. Nature. 2012, 481, 329–334. [Google Scholar] [CrossRef] [PubMed]
- Gupta, H.; Malaichamy, S.; Mallipatna, A.; Murugan, S.; Jeyabalan, N.; Suresh Babu, V.; Ghosh, A.; Ghosh, A.; Santhosh, S.; Seshagiri, S.; et al. Retinoblastoma genetics screening and clinical management. BMC Med. Genom. 2021, 14, 188. [Google Scholar] [CrossRef]
- Singh, L.; Kashyap, S. Update on pathology of retinoblastoma. Int. J. Ophthalmol. 2018, 11, 2011–2016. [Google Scholar]
- Kaliki, S.; Patel, A.; Iram, S.; Ramappa, G.; Mohamed, A.; Palkonda, V.A.R. Retinoblastoma in India: Clinical presentation and outcome in 1457 Patients (2074 Eyes). Retina 2019, 39, 379–391. [Google Scholar] [CrossRef]
- Wong, E.S.; Choy, R.W.; Zhang, Y.; Chu, W.K.; Chen, L.J.; Pang, C.P.; Yam, J.C. Global retinoblastoma survival and globe preservation: A systematic review and meta-analysis of associations with socioeconomic and health-care factors. Lancet Glob. Health 2022, 10, e380–e389. [Google Scholar] [CrossRef]
- Fabian, I.D.; Onadim, Z.; Karaa, E.; Duncan, C.; Chowdhury, T.; Scheimberg, I.; Ohnuma, I.; Reddy, M.A.; Sagoo, M.S. The management of retinoblastoma. Oncogene 2018, 37, 1551–1560. [Google Scholar] [CrossRef]
- Berry, J.L.; Kogachi, K.; Aziz, H.A.; McGovern, K.; Zolfaghari, E.; Murphree, A.L.; Jubran, R.; Kim, J.W. Risk of metastasis and orbital recurrence in advanced retinoblastoma eyes treated with systemic chemoreduction versus primary enucleation. Pediatr. Blood Cancer 2017, 64, e26270. [Google Scholar] [CrossRef]
- Canturk, S.; Qaddoumi, I.; Khetan, V.; Ma, Z.; Furmanchuk, A.; Antoneli, C.B.; Sultan, I.; Kebudi, R.; Sharma, T.; Galindo, C.R.; et al. Survival of retinoblastoma in less-developed countries impact of socioeconomic and health-related indicators. Br. J. Ophthalmol. 2010, 94, 1432–1436. [Google Scholar]
- Zeng, Y.; He, T.; Liu, J.; Li, Z.; Xie, F.; Chen, C.; Xing, Y. Bioinformatics analysis of multi-omics data identifying molecular biomarker candidates and epigenetically regulatory targets associated with retinoblastoma. Medicine 2020, 99, e23314. [Google Scholar] [CrossRef] [PubMed]
- Zhao, Y.; Gao, Y.; Xu, X.; Zhou, J.; Wang, H. Multi-omics analysis of genomics, epigenomics and transcriptomics for molecular subtypes and core genes for lung adenocarcinoma. BMC Cancer 2021, 21, 257. [Google Scholar] [CrossRef] [PubMed]
- Swiss, V.A.; Casaccia, P. Cell-context specific role of the E2F/Rb pathway in development and disease. Glia 2010, 58, 377–390. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barnum, K.J.; O’Connell, M.J. Cell cycle regulation by checkpoints. Methods Mol. Biol. 2014, 1170, 29–40. [Google Scholar]
- Kin, N.W.; Sanders, V.M. CD86 regulates IgG1 production via a CD19-dependent mechanism. J. Immunol. 2007, 179, 1516–1523. [Google Scholar] [CrossRef] [Green Version]
- McEvoy, J.D.; Dyer, M.A. Genetic and Epigenetic Discoveries in Human Retinoblastoma. Crit. Rev. Oncog. 2015, 20, 217–225. [Google Scholar]
- Liu, C.; Banister, C.E.; Weige, C.C.; Altomare, D.; Richardson, J.H.; Contreras, C.M.; Buckhaults, P.J. PRDM1 silences stem cell-related genes and inhibits proliferation of human colon tumor organoids. Proc. Natl. Acad. Sci. USA 2018, 115, E5066–E5075. [Google Scholar] [CrossRef] [Green Version]
- Etemad, S.; Petit, M.; Weiss, A.K.H.; Schrattenholz, A.; Baraldo, G.; Jansen-Durr, P. Oxaloacetate decarboxylase FAHD1—A new regulator of mitochondrial function and senescence. Mech. Ageing Dev. 2019, 177, 22–29. [Google Scholar] [CrossRef]
- Fulton, A.B.; Dodge, J.; Hansen, R.M.; Williams, T.P. The rhodopsin content of human eyes. Investig. Ophthalmol. Vis. Sci. 1999, 40, 1878–1883. [Google Scholar]
- Mears, A.J.; Kondo, M.; Swain, P.K.; Takada, Y.; Bush, R.A.; Saunders, T.L.; Sieving, P.A.; Swaroop, A. Nrl is required for rod photoreceptor development. Nat. Genet. 2001, 29, 447–452. [Google Scholar] [CrossRef]
- Cote, R.H. Characteristics of photoreceptor PDE (PDE6): Similarities and differences to PDE5. Int. J. Impot. Res. 2004, 16, S28–S33. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Napoli, J.L. Cellular retinoid binding-proteins, CRBP, CRABP, FABP5: Effects on retinoid metabolism, function and related diseases. Pharmacol. Ther. 2017, 173, 19–33. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tseng, P.L.; Chen, C.W.; Hu, K.H.; Cheng, H.C.; Lin, Y.H.; Tsai, W.H.; Cheng, T.J.; Wu, W.H.; Yeh, C.W.; Lin, C.C.; et al. The decrease of glycolytic enzyme hexokinase 1 accelerates tumor malignancy via deregulating energy metabolism but sensitizes cancer cells to 2-deoxyglucose inhibition. Oncotarget 2018, 9, 18949–18969. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lu, Y.-Y.; Wu, C.-H.; Hong, C.-H.; Chang, K.-L.; Lee, C.-H. GLUT-1 Enhances Glycolysis, Oxidative Stress, and Fibroblast Proliferation in Keloid. Life 2021, 11, 505. [Google Scholar] [CrossRef]
- Khatri, S.; Yepiskoposyan, H.; Gallo, C.A.; Tandon, P.; Plas, D.R. FOXO3a regulates glycolysis via transcriptional control of tumor suppressor TSC1. J. Biol. Chem. 2010, 285, 15960–15965. [Google Scholar]
- Christmann, M.; Verbeek, B.; Roos, W.P.; Kaina, B. O(6)-Methylguanine-DNA methyltransferase (MGMT) in normal tissues and tumors: Enzyme activity, promoter methylation and immunohistochemistry. Biochim. Biophys. Acta 2011, 1816, 179–190. [Google Scholar]
- Mallipatna, A.; Gallie, B.; Chévez-Barrios, P.; Rouic, L.; Chantada, G.; Doz, F.; Brisse, H.J.; Munier, F.L.; Albert, D.M.; Mora, J.C.; et al. AJCC Staging for Retinoblastoma, 8th ed.; Springer: Berlin, Germany, 2017; pp. 819–831. [Google Scholar]
- Linn Murphree, A. Intraocular retinoblastoma: The case for a new group classification. Ophthalmol. Clin. North Am. 2005, 18, 41–53. [Google Scholar] [CrossRef]
- Cuitino, M.C.; Pecot, T.; Sun, D.; Kladney, R.; Okano-Uchida, T.; Shinde, N.; Saeed, R.; Perez Castro, A.J.; Webb, A.; Liu, T.; et al. Two Distinct E2F Transcriptional Modules Drive Cell Cycles and Differentiation. Cell Rep. 2019, 27, 3547–3560.e5. [Google Scholar]
- Liu, Z.; Chen, S.S.; Clarke, S.; Veschi, V.; Thiele, C.J. Targeting MYCN in Pediatric and Adult Cancers. Front. Oncol. 2020, 10, 623679. [Google Scholar] [CrossRef]
- Hong, D.; Fritz, A.J.; Gordon, J.A.; Tye, C.E.; Boyd, J.R.; Tracy, K.M.; Frietze, S.E.; Carr, F.E.; Nickerson, J.A.; van Wijnen, A.J.; et al. RUNX1-dependent mechanisms in biological control and dysregulation in cancer. J. Cell Physiol. 2019, 234, 8597–8609. [Google Scholar]
- Bell, R.J.; Rube, H.T.; Kreig, A.; Mancini, A.; Fouse, S.D.; Nagarajan, R.P.; Choi, S.; Hong, C.; He, D.; Pekmezci, M.; et al. Cancer. The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer. Science 2015, 348, 1036–1039. [Google Scholar] [PubMed] [Green Version]
- Jump, D.B.; Torres-Gonzalez, M.; Olson, L.K. Soraphen A, an inhibitor of acetyl CoA carboxylase activity, interferes with fatty acid elongation. Biochem. Pharmacol. 2011, 81, 649–660. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Haberland, M.; Carrer, M.; Mokalled, M.H.; Montgomery, R.L.; Olson, E.N. Redundant control of adipogenesis by histone deacetylases 1 and 2. J. Biol. Chem. 2010, 285, 14663–14670. [Google Scholar] [PubMed] [Green Version]
- Du, H.; Wang, Y.; Zhang, Z.; Yang, J.; Zhang, J.; Zhang, Y. Fibronectin Overexpression Modulates Formation of Macrophage Foam Cells by Activating SREBP2 Involved in Endoplasmic Reticulum Stress. Cell Physiol. Biochem. 2015, 36, 1821–1834. [Google Scholar] [CrossRef]
- Chiang, J.Y. Bile acid metabolism and signaling. Compr. Physiol. 2013, 3, 1191–1212. [Google Scholar] [PubMed] [Green Version]
- Del Rey, M.J.; Valin, A.; Usategui, A.; Garcia-Herrero, C.M.; Sanchez-Arago, M.; Cuezva, J.M.; Galindo, M.; Bravo, B.; Canete, J.D.; Blanco, F.J.; et al. Hif-1alpha knockdown reduces glycolytic metabolism and induces cell death of human synovial fibroblasts under normoxic conditions. Sci. Rep. 2017, 7, 3644. [Google Scholar] [CrossRef] [Green Version]
- Miska, J.; Lee-Chang, C.; Rashidi, A.; Muroski, M.E.; Chang, A.L.; Lopez-Rosas, A.; Zhang, P.; Panek, W.K.; Cordero, A.; Han, Y.; et al. HIF-1alpha is a metabolic switch between glycolytic-driven migration and oxidative phosphorylation-driven immunosuppression of Tregs in glioblastoma. Cell Rep. 2019, 27, 226–237.e4. [Google Scholar]
- Herzig, S.; Shaw, R.J. AMPK: Guardian of metabolism and mitochondrial homeostasis. Nat. Rev. Mol. Cell Biol. 2018, 19, 121–135. [Google Scholar] [CrossRef] [Green Version]
- Hwang, J.Y.; Koch, K.W. Calcium- and myristoyl-dependent properties of guanylate cyclase-activating protein-1 and protein-2. Biochemistry 2002, 41, 13021–13028. [Google Scholar] [CrossRef]
- Giacinti, C.; Giordano, A. RB and cell cycle progression. Oncogene 2006, 25, 5220–5227. [Google Scholar]
- Sage, J.; Miller, A.L.; Perez-Mancera, P.A.; Wysocki, J.M.; Jacks, T. Acute mutation of retinoblastoma gene function is sufficient for cell cycle re-entry. Nature 2003, 424, 223–228. [Google Scholar] [CrossRef] [PubMed]
- Zeng, Z.; Cao, Z.; Tang, Y. Increased E2F2 predicts poor prognosis in patients with HCC based on TCGA data. BMC Cancer 2020, 20, 1037. [Google Scholar] [CrossRef] [PubMed]
- Sahoo, S.; Ravi Kumar, R.K.; Nicolay, B.; Mohite, O.; Sivaraman, K.; Khetan, V.; Rishi, P.; Ganesan, S.; Subramanyam, K.; Raman, K.; et al. Metabolite systems profiling identifies exploitable weaknesses in retinoblastoma. FEBS Lett. 2019, 593, 23–41. [Google Scholar] [CrossRef] [PubMed]
- Kohe, S.; Brundler, M.A.; Jenkinson, H.; Parulekar, M.; Wilson, M.; Peet, A.C.; McConville, C.M. Metabolite profiling in retinoblastoma identifies novel clinicopathological subgroups. Br. J. Cancer 2015, 113, 1216–1224. [Google Scholar] [CrossRef] [Green Version]
- Benavente, C.A.; Dyer, M.A. Genetics and epigenetics of human retinoblastoma. Annu. Rev. Pathol. 2015, 10, 547–562. [Google Scholar] [CrossRef] [Green Version]
- Elchuri, S.V.; Rajasekaran, S.; Miles, W.O. RNA-Sequencing of Primary Retinoblastoma Tumors Provides New Insights and Challenges Into Tumor Development. Front. Genet. 2018, 9, 170. [Google Scholar] [CrossRef] [Green Version]
- Chakraborty, S.; Khare, S.; Dorairaj, S.K.; Prabhakaran, V.C.; Prakash, D.R.; Kumar, A. Identification of genes associated with tumorigenesis of retinoblastoma by microarray analysis. Genomics 2007, 90, 344–353. [Google Scholar] [CrossRef]
- Galardi, A.; Colletti, M.; Lavarello, C.; Di Paolo, V.; Mascio, P.; Russo, I.; Cozza, R.; Romanzo, A.; Valente, P.; De Vito, R.; et al. Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding. Cancers 2020, 12, 1555. [Google Scholar] [CrossRef]
- Kent, L.N.; Leone, G. The broken cycle: E2F dysfunction in cancer. Nat. Rev. Cancer 2019, 19, 326–338. [Google Scholar] [CrossRef]
- Shamma, A.; Takegami, Y.; Miki, T.; Kitajima, S.; Noda, M.; Obara, T.; Okamoto, T.; Takahashi, C. Rb Regulates DNA damage response and cellular senescence through E2F-dependent suppression of N-ras isoprenylation. Cancer Cell 2009, 15, 255–269. [Google Scholar] [CrossRef] [Green Version]
- Sangwan, M.; McCurdy, S.R.; Livne-Bar, I.; Ahmad, M.; Wrana, J.L.; Chen, D.; Bremner, R. Established and new mouse models reveal E2f1 and Cdk2 dependency of retinoblastoma, and expose effective strategies to block tumor initiation. Oncogene 2012, 31, 5019–5028. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fan, X.; Wang, Y.; Jiang, T.; Liu, T.; Jin, Y.; Du, K.; Niu, Y.; Zhang, C.; Liu, Z.; Lei, Y.; et al. B-Myb accelerates colorectal cancer progression through reciprocal feed-forward transactivation of E2F2. Oncogene 2021, 40, 5613–5625. [Google Scholar] [CrossRef] [PubMed]
- Rushlow, D.E.; Mol, B.M.; Kennett, J.Y.; Yee, S.; Pajovic, S.; Theriault, B.L.; Progoda Lee, N.L.; Spencer, C.; Dimaras, H.; Corson, T.W.; et al. Characterisation of retinoblastomas without RB1 mutations: Genomic, gene expression, and clinical studies. Lancet Oncol. 2013, 14, 327–334. [Google Scholar] [CrossRef] [Green Version]
- Huang, M.; Weiss, W.A. Neuroblastoma and MYCN. Cold Spring Harb. Perspect. Med. 2013, 3, a014415. [Google Scholar] [CrossRef] [PubMed]
- Utnes, P.; Lokke, C.; Flaegstad, T.; Einvik, C. Clinically Relevant Biomarker Discovery in High-Risk Recurrent Neuroblastoma. Cancer Inform. 2019, 18, 1176935119832910. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, B.; Dai, J.X.; Pan, Y.B.; Ma, Y.B.; Chu, S.H. Examining the biomarkers and molecular mechanisms of medulloblastoma based on bioinformatics analysis. Oncol. Lett. 2019, 18, 433–441. [Google Scholar] [CrossRef] [PubMed]
- Rupp, M.; Hagenbuchner, J.; Rass, B.; Fiegl, H.; Kiechl-Kohlendorfer, U.; Obexer, P.; Ausserlechner, M.J. FOXO3-mediated chemo-protection in high-stage neuroblastoma depends on wild-type TP53 and SESN3. Oncogene 2017, 36, 6190–6203. [Google Scholar] [CrossRef] [Green Version]
- Romero-Garcia, R.; Gomez-Jaramillo, L.; Mateos, R.M.; Jimenez-Gomez, G.; Pedreno-Horrillo, N.; Foncubierta, E.; Rodriguez-Gutierrez, J.F.; Garzon, S.; Lopez, F.M.; Rodriguez, C.; et al. Differential epigenetic regulation between the alternative promoters, PRDM1alpha and PRDM1beta, of the tumour suppressor gene PRDM1 in human multiple myeloma cells. Sci. Rep. 2020, 10, 15899. [Google Scholar] [CrossRef]
- Malvi, P.; Janostiak, R.; Nagarajan, A.; Cai, G.; Wajapeyee, N. Loss of thymidine kinase 1 inhibits lung cancer growth and metastatic attributes by reducing GDF15 expression. PLoS Genet. 2019, 15, e1008439. [Google Scholar] [CrossRef] [Green Version]
- Susa, K.J.; Seegar, T.C.; Blacklow, S.C.; Kruse, A.C. A dynamic interaction between CD19 and the tetraspanin CD81 controls B cell co-receptor trafficking. eLife 2020, 9, e52337. [Google Scholar] [CrossRef]
- Schlosser, H.A.; Thelen, M.; Lechner, A.; Wennhold, K.; Garcia-Marquez, M.A.; Rothschild, S.I.; Staib, E.; Zander, T.; Beutner, D.; Gathof, B.; et al. B cells in esophago-gastric adenocarcinoma are highly differentiated, organize in tertiary lymphoid structures and produce tumor-specific antibodies. Oncoimmunology 2019, 8, e1512458. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Halliday, N.; Williams, C.; Kennedy, A.; Waters, E.; Pesenacker, A.M.; Soskic, B.; Hinze, C.; Hou, T.Z.; Rowshanravan, B.; Janman, D.; et al. CD86 Is a Selective CD28 Ligand Supporting FoxP3+ Regulatory T Cell Homeostasis in the Presence of High Levels of CTLA-4. Front. Immunol. 2020, 11, 600000. [Google Scholar] [CrossRef] [PubMed]
- Liu, J.; Ottaviani, D.; Sefta, M.; Desbrousses, C.; Chapeaublanc, E.; Aschero, R. A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression. Nat. Commun. 2021, 12, 5578. [Google Scholar] [CrossRef] [PubMed]
- Kapatai, G.; Brundler, M.A.; Jenkinson, H.; Kearns, P.; Parulekar, M.; Peet, A.C.; McConville, C.M. Gene expression profiling identifies different sub-types of retinoblastoma. Br. J. Cancer 2013, 109, 512–525. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, X.L.; Fang, Y.; Lee, T.C.; Forrest, D.; Gregory-Evans, C.; Almeida, D.; Liu, A.; Jhanwar, S.C.; Abramson, D.H.; Cobrinik, D. Retinoblastoma has properties of a cone precursor tumor and depends upon cone-specific MDM2 signaling. Cell 2009, 137, 1018–1031. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, H.; Chang, Y.; Schweers, B.; Dyer, M.A.; Zhang, X.; Hayward, S.W.; Goodrich, D.W. An E2F binding-deficient Rb1 protein partially rescues developmental defects associated with Rb1 nullizygosity. Mol. Cell Biol. 2006, 26, 1527–1537. [Google Scholar] [CrossRef] [Green Version]
- Tanner, L.B.; Goglia, A.G.; Wei, M.H.; Sehgal, T.; Parsons, L.R.; Park, J.O.; White, E.; Toettcher, J.E.; Rabinowitz, J.D. Four Key Steps Control Glycolytic Flux in Mammalian Cells. Cell Syst. 2018, 7, 49–62.e8. [Google Scholar] [CrossRef]
- He, X.; Lin, X.; Cai, M.; Zheng, X.; Lian, L.; Fan, D.; Wu, X.; Lan, P.; Wang, J. Overexpression of Hexokinase 1 as a poor prognosticator in human colorectal cancer. Tumor Biol. 2016, 37, 3887–3895. [Google Scholar] [CrossRef]
- Amendola, C.R.; Mahaffey, J.P.; Parker, S.J.; Ahearn, I.M.; Chen, W.-C.; Zhou, M.; Court, H.; Shi, J.; Mendoza, S.L.; Morten, M.J.; et al. KRAS4A directly regulates hexokinase 1. Nature 2019, 576, 482–486. [Google Scholar] [CrossRef]
- Clem, B.F.; Chesney, J. Molecular pathways: Regulation of metabolism by RB. Clin. Cancer Res. 2012, 18, 6096–6100. [Google Scholar] [CrossRef] [Green Version]
ID | Sex | Laterality | Age at Presentation | Clinical Risk | IIRC Group | AJCC Staging |
---|---|---|---|---|---|---|
P1 | M | Bilateral | 15 months | Advanced | Group E | cT3b |
P2 | F | Unilateral | 20 months | Advanced | Group E | cT3b |
P3 | M | Unilateral | 24 months | Advanced | Group E | cT3a |
P4 | F | Bilateral | 4 months | Advanced | Group E | cT3b |
P5 | M | Bilateral | 30 months | Advanced | Group E | cT3b |
P6 | F | Bilateral | 21 months | Non-advanced | Group D | cT2b |
P7 | F | Unilateral | 28 months | Non-advanced | Group D | cT2b |
P8 | M | Unilateral | 20 months | Non-advanced | Group D | cT2b |
P9 | M | Unilateral | 21 months | Non-advanced | Group D | cT2a |
Control 1 | F | NA | 3 months | Cardiac Arrest (no ocular complications) | ||
Control 2 | F | NA | 2 months | Multiple organ dysfunction (no ocular complications) |
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Babu, V.S.; Mallipatna, A.; SA, D.; Dudeja, G.; Kannan, R.; Shetty, R.; Nair, A.P.; Gundimeda, S.; Chaurasia, S.S.; Verma, N.K.; et al. Integrated Analysis of Cancer Tissue and Vitreous Humor from Retinoblastoma Eyes Reveals Unique Tumor-Specific Metabolic and Cellular Pathways in Advanced and Non-Advanced Tumors. Cells 2022, 11, 1668. https://doi.org/10.3390/cells11101668
Babu VS, Mallipatna A, SA D, Dudeja G, Kannan R, Shetty R, Nair AP, Gundimeda S, Chaurasia SS, Verma NK, et al. Integrated Analysis of Cancer Tissue and Vitreous Humor from Retinoblastoma Eyes Reveals Unique Tumor-Specific Metabolic and Cellular Pathways in Advanced and Non-Advanced Tumors. Cells. 2022; 11(10):1668. https://doi.org/10.3390/cells11101668
Chicago/Turabian StyleBabu, Vishnu Suresh, Ashwin Mallipatna, Deepak SA, Gagan Dudeja, Ramaraj Kannan, Rohit Shetty, Archana Padmanabhan Nair, Seetharamanjaneyulu Gundimeda, Shyam S. Chaurasia, Navin Kumar Verma, and et al. 2022. "Integrated Analysis of Cancer Tissue and Vitreous Humor from Retinoblastoma Eyes Reveals Unique Tumor-Specific Metabolic and Cellular Pathways in Advanced and Non-Advanced Tumors" Cells 11, no. 10: 1668. https://doi.org/10.3390/cells11101668
APA StyleBabu, V. S., Mallipatna, A., SA, D., Dudeja, G., Kannan, R., Shetty, R., Nair, A. P., Gundimeda, S., Chaurasia, S. S., Verma, N. K., Lakshminarayanan, R., Heymans, S., Barathi, V. A., Guha, N., & Ghosh, A. (2022). Integrated Analysis of Cancer Tissue and Vitreous Humor from Retinoblastoma Eyes Reveals Unique Tumor-Specific Metabolic and Cellular Pathways in Advanced and Non-Advanced Tumors. Cells, 11(10), 1668. https://doi.org/10.3390/cells11101668