Labyrinthin Expression Is Associated with Poor Prognosis in Patients with Non-Small-Cell Lung Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Tissue Microarrays (TMAs)
2.2. Immunohistochemistry (IHC) Stain
2.3. Statistical Analysis for IHC Data
2.4. LAB RNA Expression Analysis
3. Results
3.1. Patient Characteristics and LAB Expression in NSCLC
3.2. High LAB Expression Was Associated with Poor Prognosis in NSCLC
3.3. LAB Expression in Histology Subgroups of NSCLC
3.4. High LAB RNA Expression Was Associated with Poor Prognosis in Patients with LUAD
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Babich, M.; Sharma, A.; Li, T.; Radosevich, J.A. Labyrinthin: A distinct pan-adenocarcinoma diagnostic and immunotherapeutic tumor specific antigen. Heliyon 2022, 8, e08988. [Google Scholar] [CrossRef] [PubMed]
- Zheng, W.; Wang, X.; Hu, J.; Bai, B.; Zhu, H. Diverse molecular functions of aspartate β-hydroxylase in cancer (Review). Oncol. Rep. 2020, 44, 2364–2372. [Google Scholar] [CrossRef] [PubMed]
- Combs, S.; Radosevich, J.; Ma, Y.; Lee, I.; Gould, V.; Battifora, H.; Rosen, S. Expression of the Antigenic Determinant Recognized by the Monoclonal Antibody 44-3A6 on Select Human Adenocarcinomas and Normal Human Tissues. Tumor Biol. 1988, 9, 116–122. [Google Scholar] [CrossRef] [PubMed]
- Siddiqui, F.; Iqbal, Z.; Radosevich, J. Changes in the Expression of the Tumor-Associated Antigen Recognized by Monoclonal Antibody 44–3A6 in A549 Cells due to Calcium. Tumor Biol. 1992, 13, 142–151. [Google Scholar] [CrossRef]
- Padar, S.; Van Breemen, C.; Thomas, D.W.; Uchizono, J.; Livesey, J.C.; Rahimian, R. Differential regulation of calcium homeostasis in adenocarcinoma cell line A549 and its Taxol-resistant subclone. Br. J. Pharmacol. 2004, 142, 305–316. [Google Scholar] [CrossRef]
- Cajulis, R.S.; Szumel, R.; Frias-Hidvegi, D.; Combs, S.G.; Radosevich, J.A. Monoclonal antibody 44-3A6 as an adjunct in cytodiagnosis of adenocarcinomas in body fluids. Diagn. Cytopathol. 1993, 9, 179–183. [Google Scholar] [CrossRef]
- Spagnolo, D.V.; Whitaker, D.; Carrello, S.; Radosevich, J.A.; Rosen, S.T.; Gould, V.E. The Use of Monoclonal Antibody 44-3A6 in Cell Blocks in the Diagnosis of Lung Carcinoma, Carcinomas Metastatic to Lung and Pleura, and Pleural Malignant Mesothelioma. Am. J. Clin. Pathol. 1991, 95, 322–329. [Google Scholar] [CrossRef]
- Ma, W.; Chen, S.; Ogihara, N.L.; Huynh, J.; Yen, A.; Kelly, K.; Lara, P.N.; Radosevich, J.A.; Babich, M.; Li, T. A first-in-human, phase I, open-label study of a novel cancer vaccine labvax 3(22)-23 and adjuvant GM-CSF in patients with advanced stage adenocarcinomas. J. Clin. Oncol. 2022, 40, TPS2700. [Google Scholar] [CrossRef]
- Reck, M.; Rabe, K.F. Precision Diagnosis and Treatment for Advanced Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2017, 377, 849–861. [Google Scholar] [CrossRef]
- Postmus, P.E.; Kerr, K.M.; Oudkerk, M.; Senan, S.; Waller, D.A.; Vansteenkiste, J.; Escriu, C.; Peters, S.; ESMO Guidelines Committee. Early and Locally Advanced Non-Small-Cell Lung Cancer (NSCLC): ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. Ann. Oncol. 2017, 28, iv1–iv21. [Google Scholar] [CrossRef]
- Knight, S.B.; Phil, A.; Crosbie, P.A.; Balata, H.; Chudziak, J.; Hussell, T.; Dive, C. Progress and prospects of early detection in lung cancer. Open Biol. 2017, 7, 170070. [Google Scholar] [CrossRef]
- Tan, W.-L.; Jain, A.; Takano, A.; Newell, E.W.; Iyer, N.G.; Lim, W.-T.; Tan, E.-H.; Zhai, W.; Hillmer, A.M.; Tam, W.L.; et al. Novel therapeutic targets on the horizon for lung cancer. Lancet Oncol. 2016, 17, e347–e362. [Google Scholar] [CrossRef]
- Ullah, A.; Leong, S.W.; Wang, J.; Wu, Q.; Ghauri, M.A.; Sarwar, A.; Su, Q.; Zhang, Y. Cephalomannine inhibits hypoxia-induced cellular function via the suppression of APEX1/HIF-1α interaction in lung cancer. Cell Death Dis. 2021, 12, 490. [Google Scholar] [CrossRef]
- Iqbal, H.; Menaa, F.; Khan, N.U.; Razzaq, A.; Khan, Z.U.; Ullah, K.; Kamal, R.; Sohail, M.; Thiripuranathar, G.; Uzair, B.; et al. Two Promising Anti-Cancer Compounds, 2-Hydroxycinnaldehyde and 2- Benzoyloxycinnamaldehyde: Where do we stand? Comb. Chem. High Throughput Screen. 2022, 25, 808–818. [Google Scholar] [CrossRef]
- Ullah, A.; Aziz, T.; Ullah, N.; Nawaz, T. Molecular mechanisms of Sanguinarine in cancer prevention and treatment. Anti Cancer Agents Med. Chem. 2022, 22, 3. [Google Scholar] [CrossRef]
- Li, Q.; Ma, W.; Chen, S.; Tian, E.C.; Wei, S.; Fan, R.R.; Wang, T.; Zhou, C.; Li, T. High integrin α3 expression is associated with poor prognosis in patients with non-small cell lung cancer. Transl. Lung Cancer Res. 2020, 9, 1361–1378. [Google Scholar] [CrossRef]
- Austin, P.C. The performance of different propensity score methods for estimating marginal hazard ratios. Stat. Med. 2013, 32, 2837–2849. [Google Scholar] [CrossRef]
- Imbens, G. The role of the propensity score in estimating dose-response functions. Biometrika 2000, 87, 706–710. [Google Scholar] [CrossRef]
- Rubin, D.B. Multiple Imputation for Nonresponse in Surveys; John Wiley & Sons: Hoboken, NJ, USA, 1987. [Google Scholar]
- Sun, W.; Duan, T.; Ye, P.; Chen, K.; Zhang, G.; Lai, M.; Zhang, H. TSVdb: A web-tool for TCGA splicing variants analysis. BMC Genom. 2018, 19, 405. [Google Scholar] [CrossRef]
- Mortazavi, A.; Williams, B.A.; McCue, K.; Schaeffer, L.; Wold, B. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat. Methods 2008, 5, 621–628. [Google Scholar] [CrossRef]
- Kassambara, A.; Kosinski, M.; Biecek, P.; Fabian, S. Survminer: Drawing Survival Curves Using ‘Ggplot2’ R Package Version 0.4.4. 2019. Available online: https://www.cranr-projectorg/package=survminer (accessed on 11 October 2022).
- Li, L.; Goedegebuure, S.; Gillanders, W. Preclinical and clinical development of neoantigen vaccines. Ann. Oncol. 2017, 28, xii11–xii17. [Google Scholar] [CrossRef] [PubMed]
- Ott, P.A.; Hu, Z.; Keskin, D.B.; Shukla, S.A.; Sun, J.; Bozym, D.J.; Zhang, W.; Luoma, A.; Giobbie-Hurder, A.; Peter, L.; et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 2017, 547, 217–221, Erratum in Nature 2018, 555, 402. [Google Scholar] [CrossRef] [PubMed]
- Schumacher, T.N.; Schreiber, R.D. Neoantigens in cancer immunotherapy. Science 2015, 348, 69–74. [Google Scholar] [CrossRef] [PubMed]
- Blass, E.; Ott, P.A. Advances in the development of personalized neoantigen-based therapeutic cancer vaccines. Nat. Rev. Clin. Oncol. 2021, 18, 215–229. [Google Scholar] [CrossRef]
- Luu, M.; Sabo, E.; de la Monte, S.M.; Greaves, W.; Wang, J.; Tavares, R.; Simao, L.; Wands, J.R.; Resnick, M.B.; Wang, L. Prognostic value of aspartyl (asparaginyl)-β-hydroxylase/humbug expression in non–small cell lung carcinoma. Hum. Pathol. 2009, 40, 639–644. [Google Scholar] [CrossRef] [Green Version]
Univariate | Multivariate | |||||
---|---|---|---|---|---|---|
HR | (95% CI) | p-Value | HR | (95% CI) | p-Value | |
IHC Score of LAB (1+): LAB > 5% vs. LAB ≤ 5% | 3.55 | 2.30–5.40 | <0.0001 | 5.9 | 2.61–13.34 | <0.0001 |
Age (in years old): ≥65 vs. <65 | 1.55 | 1.06–2.27 | 0.02 | 1.64 | 1.06–2.53 | 0.028 |
Smoke: No vs. Yes | 1.52 | 1.02–2.28 | 0.039 | 1.27 | 0.76–2.77 | 0.36 |
COPD: Yes vs. No | 1.41 | 0.94–2.21 | 0.11 | 1.48 | 0.87–2.52 | 0.15 |
Histology: Squamous vs. Adenocarcinoma | 0.87 | 0.56–1.33 | 0.51 | 0.89 | 0.56–1.41 | 0.64 |
Differentiation Grade: Poor (III) vs Well (I) ~Moderate (II) | 1.19 | 0.75–1.88 | 0.42 | 1.20 | 0.75–1.90 | 0.45 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ma, W.; Zeng, J.; Montoya, D.J.; Toomey, K.; Zhou, C.; Chen, S.; Liu, D.; Babich, M.; Radosevich, J.A.; Li, T. Labyrinthin Expression Is Associated with Poor Prognosis in Patients with Non-Small-Cell Lung Cancer. Cancers 2023, 15, 924. https://doi.org/10.3390/cancers15030924
Ma W, Zeng J, Montoya DJ, Toomey K, Zhou C, Chen S, Liu D, Babich M, Radosevich JA, Li T. Labyrinthin Expression Is Associated with Poor Prognosis in Patients with Non-Small-Cell Lung Cancer. Cancers. 2023; 15(3):924. https://doi.org/10.3390/cancers15030924
Chicago/Turabian StyleMa, Weijie, Jie Zeng, Dennis J. Montoya, Kyra Toomey, Chihong Zhou, Shuai Chen, Dingning Liu, Michael Babich, James A. Radosevich, and Tianhong Li. 2023. "Labyrinthin Expression Is Associated with Poor Prognosis in Patients with Non-Small-Cell Lung Cancer" Cancers 15, no. 3: 924. https://doi.org/10.3390/cancers15030924
APA StyleMa, W., Zeng, J., Montoya, D. J., Toomey, K., Zhou, C., Chen, S., Liu, D., Babich, M., Radosevich, J. A., & Li, T. (2023). Labyrinthin Expression Is Associated with Poor Prognosis in Patients with Non-Small-Cell Lung Cancer. Cancers, 15(3), 924. https://doi.org/10.3390/cancers15030924