Machine Learning-derived Multi-omics Prognostic Signature of Pyroptosis-related lncRNA with Regard to ZKSCAN2-DT and Tumor Immune Infiltration in Colorectal Cancer


Дәйексөз келтіру

Толық мәтін

Аннотация

Background:Colorectal cancer (CRC) has become the most prevalent gastrointestinal malignant tumor, ranking third (10.2%) in incidence and second (9.2%) in death among all malignancies globally. The most common histological subtype of CRC is colon adenocarcinoma (COAD), although the cause of CRC remains unknown, as there are no valid biomarkers.

Methods:A thorough investigation was used to build a credible biomolecular risk model based on the pyroptosis-associated lncRNAs discovered for COAD prediction. Furthermore, Cibersort and Tumor Immune Dysfunction and Exclusion (TIDE), the methods of exploring tumor immune infiltration, were adopted in our paper to detect the effects of differential lncRNAs on the tumor microenvironment. Finally, quantitative real-time polymerase chain reaction (qPCR), as the approach of exploring expressions, was utilized on four different cell lines.

Results:Seven pyroptosis-related lncRNAs have been identified as COAD predictive risk factors. Cox analysis, both univariate and multivariate, revealed that the established signature might serve as a novel independent factor with prognostic meaning in COAD patients. ZKSCAN2-DT was shown to be considerably overexpressed in the COAD cell line when compared to normal human colonic epithelial cells. Furthermore, ssGSEA analysis results revealed that the immune infiltration percentage of most immune cells dropped considerably as ZKSCAN2-DT expression increased, implying that ZKSCAN2-DT may play an important role in COAD immunotherapy.

Conclusion:Our research is the first to identify pyroptosis-related lncRNAs connected with COAD patient prognosis and to construct a predictive prognosis signature, directing COAD patient prognosis in therapeutic interventions.

Авторлар туралы

Jiamin Chen

Department of Gastroenterology, The Second Affiliated Hospital,, Zhejiang University School of Medicine

Email: info@benthamscience.net

Dan Jin

Department of Gastroenterology, The Second Affiliated Hospital,, Zhejiang University School of Medicine

Email: info@benthamscience.net

Liming Shao

Department of Gastroenterology, The Second Affiliated Hospital,, Zhejiang University School of Medicine

Email: info@benthamscience.net

Lingling Wang

Institute of Immunology, Zhejiang University School of Medicine

Email: info@benthamscience.net

Liuzhi Zhou

Department of Surgical Oncology, Sir Run Run Shaw Hospital,, Zhejiang University

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Jianting Cai

Department of Gastroenterology, The Second Affiliated Hospital,, Zhejiang University School of Medicine

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Әдебиет тізімі

  1. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424. doi: 10.3322/caac.21492 PMID: 30207593
  2. Siegel, R.L.; Miller, K.D.; Goding Sauer, A.; Fedewa, S.A.; Butterly, L.F.; Anderson, J.C.; Cercek, A.; Smith, R.A.; Jemal, A. Colorectal cancer statistics, 2020. CA Cancer J. Clin., 2020, 70(3), 145-164. doi: 10.3322/caac.21601 PMID: 32133645
  3. Baidoun, F.; Elshiwy, K.; Elkeraie, Y.; Merjaneh, Z.; Khoudari, G.; Sarmini, M.T.; Gad, M.; Al-Husseini, M.; Saad, A. Colorectal cancer epidemiology: Recent trends and impact on outcomes. Curr. Drug Targets, 2021, 22(9), 998-1009. doi: 10.2174/18735592MTEx9NTk2y PMID: 33208072
  4. Villariba-Tolentino, C.; Cariño, A.M.; Notarte, K.I.; Macaranas, I.; Fellizar, A.; Tomas, R.C.; Angeles, L.M.; Abanilla, L.; Lim, A.; Aguilar, M.K.C.; Albano, P.M. pks+ Escherichia coli more prevalent in benign than malignant colorectal tumors. Mol. Biol. Rep., 2021, 48(7), 5451-5458. doi: 10.1007/s11033-021-06552-1 PMID: 34297324
  5. Wang, J.; Li, S.; Liu, Y.; Zhang, C.; Li, H.; Lai, B. Metastatic patterns and survival outcomes in patients with stage IV colon cancer: A population‐based analysis. Cancer Med., 2020, 9(1), 361-373. doi: 10.1002/cam4.2673 PMID: 31693304
  6. Shi, J.; Gao, W.; Shao, F. Pyroptosis: Gasdermin-mediated programmed necrotic cell death. Trends Biochem. Sci., 2017, 42(4), 245-254. doi: 10.1016/j.tibs.2016.10.004 PMID: 27932073
  7. Liu, X.; Xia, S.; Zhang, Z.; Wu, H.; Lieberman, J. Channelling inflammation: Gasdermins in physiology and disease. Nat. Rev. Drug Discov., 2021, 20(5), 384-405. doi: 10.1038/s41573-021-00154-z PMID: 33692549
  8. Broz, P.; Pelegrín, P.; Shao, F. The gasdermins, a protein family executing cell death and inflammation. Nat. Rev. Immunol., 2020, 20(3), 143-157. doi: 10.1038/s41577-019-0228-2 PMID: 31690840
  9. Miguchi, M.; Hinoi, T.; Shimomura, M.; Adachi, T.; Saito, Y.; Niitsu, H.; Kochi, M.; Sada, H.; Sotomaru, Y.; Ikenoue, T.; Shigeyasu, K.; Tanakaya, K.; Kitadai, Y.; Sentani, K.; Oue, N.; Yasui, W.; Ohdan, H.; Gasdermin, C. Gasdermin C is upregulated by inactivation of transforming growth factor β receptor type II in the presence of mutated Apc, promoting colorectal cancer proliferation. PLoS One, 2016, 11(11), e0166422. doi: 10.1371/journal.pone.0166422 PMID: 27835699
  10. Kim, M.S.; Chang, X.; Yamashita, K.; Nagpal, J.K.; Baek, J.H.; Wu, G.; Trink, B.; Ratovitski, E.A.; Mori, M.; Sidransky, D. Aberrant promoter methylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma. Oncogene, 2008, 27(25), 3624-3634. doi: 10.1038/sj.onc.1211021 PMID: 18223688
  11. Tan, G.; Huang, C.; Chen, J.; Zhi, F. HMGB1 released from GSDME-mediated pyroptotic epithelial cells participates in the tumorigenesis of colitis-associated colorectal cancer through the ERK1/2 pathway. J. Hematol. Oncol., 2020, 13(1), 149. doi: 10.1186/s13045-020-00985-0 PMID: 33160389
  12. Zhang, Z.; Zhang, Y.; Xia, S.; Kong, Q.; Li, S.; Liu, X.; Junqueira, C.; Meza-Sosa, K.F.; Mok, T.M.Y.; Ansara, J.; Sengupta, S.; Yao, Y.; Wu, H.; Lieberman, J. Gasdermin E suppresses tumour growth by activating anti-tumour immunity. Nature, 2020, 579(7799), 415-420. doi: 10.1038/s41586-020-2071-9 PMID: 32188940
  13. Hou, J.; Hsu, J.M.; Hung, M.C. Molecular mechanisms and functions of pyroptosis in inflammation and antitumor immunity. Mol. Cell, 2021, 81(22), 4579-4590. doi: 10.1016/j.molcel.2021.09.003 PMID: 34562371
  14. Wang, Y.; Gao, W.; Shi, X.; Ding, J.; Liu, W.; He, H.; Wang, K.; Shao, F. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature, 2017, 547(7661), 99-103. doi: 10.1038/nature22393 PMID: 28459430
  15. Zhang, X.; Zhang, H. Chemotherapy drugs induce pyroptosis through caspase-3-dependent cleavage of GSDME. Sci. China Life Sci., 2018, 61(6), 739-740. doi: 10.1007/s11427-017-9158-x PMID: 29497957
  16. 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. doi: 10.1038/s41575-019-0126-x PMID: 30886395
  17. Mercer, T.R.; Dinger, M.E.; Mattick, J.S. Long non-coding RNAs: Insights into functions. Nat. Rev. Genet., 2009, 10(3), 155-159. doi: 10.1038/nrg2521 PMID: 19188922
  18. Zhang, G.; Sun, J.; Zhang, X. A novel Cuproptosis-related LncRNA signature to predict prognosis in hepatocellular carcinoma. Sci. Rep., 2022, 12(1), 11325. doi: 10.1038/s41598-022-15251-1 PMID: 35790864
  19. Notarte, K.I.; Senanayake, S.; Macaranas, I.; Albano, P.M.; Mundo, L.; Fennell, E.; Leoncini, L.; Murray, P. MicroRNA and other non-coding RNAs in epstein–barr virus-associated cancers. Cancers., 2021, 13(15), 3909. doi: 10.3390/cancers13153909 PMID: 34359809
  20. Denaro, N.; Merlano, M.C.; Lo Nigro, C. Long noncoding RNA s as regulators of cancer immunity. Mol. Oncol., 2019, 13(1), 61-73. doi: 10.1002/1878-0261.12413 PMID: 30499165
  21. He, D.; Zheng, J.; Hu, J.; Chen, J.; Wei, X. Long non-coding RNAs and pyroptosis. Clin. Chim. Acta, 2020, 504, 201-208. doi: 10.1016/j.cca.2019.11.035 PMID: 31794769
  22. Zhang, X.; Sun, S.; Pu, J.K.S.; Tsang, A.C.O.; Lee, D.; Man, V.O.Y.; Lui, W.M.; Wong, S.T.S.; Leung, G.K.K. Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol. Dis., 2012, 48(1), 1-8. doi: 10.1016/j.nbd.2012.06.004 PMID: 22709987
  23. Wu, J.; Zhu, Y.; Luo, M.; Li, L. Comprehensive analysis of pyroptosis-related genes and tumor microenvironment infiltration characterization in breast cancer. Front. Immunol., 2021, 12, 748221. doi: 10.3389/fimmu.2021.748221 PMID: 34659246
  24. Lossos, I.S.; Czerwinski, D.K.; Alizadeh, A.A.; Wechser, M.A.; Tibshirani, R.; Botstein, D.; Levy, R. Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N. Engl. J. Med., 2004, 350(18), 1828-1837. doi: 10.1056/NEJMoa032520 PMID: 15115829
  25. Blanche, P.; Dartigues, J.F.; Jacqmin-Gadda, H. Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks. Stat. Med., 2013, 32(30), 5381-5397. doi: 10.1002/sim.5958 PMID: 24027076
  26. Newman, A.M.; Liu, C.L.; Green, M.R.; Gentles, A.J.; Feng, W.; Xu, Y.; Hoang, C.D.; Diehn, M.; Alizadeh, A.A. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods, 2015, 12(5), 453-457. doi: 10.1038/nmeth.3337 PMID: 25822800
  27. Xiao, B.; Liu, L.; Li, A.; Xiang, C.; Wang, P.; Li, H.; Xiao, T. Identification and verification of immune-related gene prognostic signature based on ssGSEA for osteosarcoma. Front. Oncol., 2020, 10, 607622. doi: 10.3389/fonc.2020.607622 PMID: 33384961
  28. Cao, R.; Yuan, L.; Ma, B.; Wang, G.; Tian, Y. Tumour microenvironment (TME) characterization identified prognosis and immunotherapy response in muscle-invasive bladder cancer (MIBC). Cancer Immunol. Immunother., 2021, 70(1), 1-18. doi: 10.1007/s00262-020-02649-x PMID: 32617668
  29. Goodman, A.; Patel, S.P.; Kurzrock, R. PD-1–PD-L1 immune-checkpoint blockade in B-cell lymphomas. Nat. Rev. Clin. Oncol., 2017, 14(4), 203-220. doi: 10.1038/nrclinonc.2016.168 PMID: 27805626
  30. Nishino, M.; Ramaiya, N.H.; Hatabu, H.; Hodi, F.S. Monitoring immune-checkpoint blockade: Response evaluation and biomarker development. Nat. Rev. Clin. Oncol., 2017, 14(11), 655-668. doi: 10.1038/nrclinonc.2017.88 PMID: 28653677
  31. Zhai, L.; Ladomersky, E.; Lenzen, A.; Nguyen, B.; Patel, R.; Lauing, K.L.; Wu, M.; Wainwright, D.A. IDO1 in cancer: A Gemini of immune checkpoints. Cell. Mol. Immunol., 2018, 15(5), 447-457. doi: 10.1038/cmi.2017.143 PMID: 29375124
  32. Kim, J.E.; Patel, M.A.; Mangraviti, A.; Kim, E.S.; Theodros, D.; Velarde, E.; Liu, A.; Sankey, E.W.; Tam, A.; Xu, H.; Mathios, D.; Jackson, C.M.; Harris-Bookman, S.; Garzon-Muvdi, T.; Sheu, M.; Martin, A.M.; Tyler, B.M.; Tran, P.T.; Ye, X.; Olivi, A.; Taube, J.M.; Burger, P.C.; Drake, C.G.; Brem, H.; Pardoll, D.M.; Lim, M. Combination therapy with Anti-PD-1, Anti-TIM-3, and focal radiation results in regression of murine gliomas. Clin. Cancer Res., 2017, 23(1), 124-136. doi: 10.1158/1078-0432.CCR-15-1535 PMID: 27358487
  33. Sun, D.; Wang, J.; Han, Y.; Dong, X.; Ge, J.; Zheng, R.; Shi, X.; Wang, B.; Li, Z.; Ren, P.; Sun, L.; Yan, Y.; Zhang, P.; Zhang, F.; Li, T.; Wang, C. TISCH: A comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment. Nucleic Acids Res., 2021, 49(D1), D1420-D1430. doi: 10.1093/nar/gkaa1020 PMID: 33179754
  34. Raskov, H.; Søby, J.H.; Troelsen, J.; Bojesen, R.D.; Gögenur, I. Driver gene mutations and epigenetics in colorectal cancer. Ann. Surg., 2020, 271(1), 75-85. doi: 10.1097/SLA.0000000000003393 PMID: 31188207
  35. Tang, R.; Xu, J.; Zhang, B.; Liu, J.; Liang, C.; Hua, J.; Meng, Q.; Yu, X.; Shi, S. Ferroptosis, necroptosis, and pyroptosis in anticancer immunity. J. Hematol. Oncol., 2020, 13(1), 110. doi: 10.1186/s13045-020-00946-7 PMID: 32778143
  36. Huang, M.; Chen, Y.; Han, D.; Lei, Z.; Chu, X. Role of the zinc finger and SCAN domain-containing transcription factors in cancer. Am. J. Cancer Res., 2019, 9(5), 816-836. PMID: 31218096
  37. Bi, J.; Liu, H.; Dong, W.; Xie, W.; He, Q.; Cai, Z.; Huang, J.; Lin, T. Correction to: Circular RNA circ-ZKSCAN1 inhibits bladder cancer progression through miR-1178-3p/p21 axis and acts as a prognostic factor of recurrence. Mol. Cancer, 2020, 19(1), 148. doi: 10.1186/s12943-020-01265-8 PMID: 33046073
  38. Benedix, F.; Kube, R.; Meyer, F.; Schmidt, U.; Gastinger, I.; Lippert, H. Colon/rectum carcinomas study, comparison of 17,641 patients with right- and left-sided colon cancer: Differences in epidemiology, perioperative course, histology, and survival. Dis. Colon Rectum, 2010, 53(1), 57-64. doi: 10.1007/DCR.0b013e3181c703a4

Қосымша файлдар

Қосымша файлдар
Әрекет
1. JATS XML

© Bentham Science Publishers, 2024