CPSF3 is a promising prognostic biomarker and predicts recurrence of non‑small cell lung cancer

Ning,Yue; Liu,Wanxia; Guan,Xiaoying; Xie,Xiaobin; Zhang,Yajie

doi:10.3892/ol.2019.10659

CPSF3 is a promising prognostic biomarker and predicts recurrence of non‑small cell lung cancer

Authors:
- Yue Ning
- Wanxia Liu
- Xiaoying Guan
- Xiaobin Xie
- Yajie Zhang
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Affiliations: Department of Pathology, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China, Center for Transforming Medicine, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, P.R. China, Department of Experimental Nuclear Medicine and Radiology, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China
Published online on: July 24, 2019 https://doi.org/10.3892/ol.2019.10659
Pages: 2835-2844
Copyright: © Ning et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cleavage polyadenylation specificity factor (CPSF) is the core component of the 3'‑end processing complex, which determines the site of 3'‑end cleavage interactions of specific sequence elements within pre‑mRNAs. The present study revealed that all members of the CPSF complex were overexpressed in lung cancer tissue from The Cancer Genome Atlas (TCGA) Lung Cancer Cohort compared with normal lung tissue. Analysis of overall survival and recurrence‑free survival verified that only CPSF3 was associated with prognosis and recurrence of lung adenocarcinoma (LUAD), and thus could be a promising biomarker. Additionally, receiver operating characteristic curve analysis revealed that CPSF3 may function as a diagnostic biomarker to distinguish between two histological subtypes of non‑small cell lung cancer. Furthermore, analysis of the association of CPSF3 expression with clinicopathological parameters indicated that CPSF3 was associated with smoking history, tumor diameter, lymph node metastasis, clinical stage and radiation therapy in LUAD. Additionally, analysis of the DNA methylation data of the TCGA‑LUAD Cohort revealed that CPSF3 DNA CpG sites (cg12057242 and cg25739938) were generally hypomethylated in LUAD compared with normal lung tissue. Correlation analysis identified the CPSF3 DNA CpG site cg25739938 to be negatively correlated with CPSF3 expression, while no correlation was identified with cg12057242. In addition, correlation analysis demonstrated that the overexpression of CPSF3 was correlated with CPSF3 DNA copy number variants (CNAs). The findings indicate that abnormal expression of CPSF3 may be caused by DNA CNAs; and DNA hypermethylation and function may be a promising diagnostic and prognostic indicator for LUAD.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
2	Thomas A, Liu SV, Subramaniam DS and Giaccone G: Refining the treatment of NSCLC according to histological and molecular subtypes. Nat Rev Clin Oncol. 12:511–526. 2015. View Article : Google Scholar : PubMed/NCBI
3	Gadgeel SM, Ramalingam SS and Kalemkerian GP: Treatment of lung cancer. Radiol Clin North Am. 50:961–974. 2012. View Article : Google Scholar : PubMed/NCBI
4	Daga A, Ansari A, Patel S, Mirza S, Rawal R and Umrania V: Current drugs and drug targets in Non-small cell lung cancer: Limitations and opportunities. Asian Pac J Cancer Prev. 16:4147–4156. 2015. View Article : Google Scholar : PubMed/NCBI
5	Godin-Heymann N, Ulkus L, Brannigan BW, McDermott U, Lamb J, Maheswaran S, Settleman J and Haber DA: The T790M ‘gatekeeper’ mutation in EGFR mediates resistance to low concentrations of an irreversible EGFR inhibitor. Mol Cancer Ther. 7:874–879. 2008. View Article : Google Scholar : PubMed/NCBI
6	Coate LE, John T, Tsao MS and Shepherd FA: Molecular predictive and prognostic markers in non-small-cell lung cancer. Lancet Oncol. 10:1001–1010. 2009. View Article : Google Scholar : PubMed/NCBI
7	Yu HA, Sima CS, Huang J, Solomon SB, Rimner A, Paik P, Pietanza MC, Azzoli CG, Rizvi NA, Krug LM, et al: Local therapy with continued EGFR tyrosine kinase inhibitor therapy as a treatment strategy in EGFR-mutant advanced lung cancers that have developed acquired resistance to EGFR tyrosine kinase inhibitors. J Thorac Oncol. 8:346–351. 2013. View Article : Google Scholar : PubMed/NCBI
8	Soucheray M, Capelletti M, Pulido I, Kuang Y, Paweletz CP, Becker JH, Kikuchi E, Xu C, Patel TB, Al-Shahrour F, et al: Intratumoral heterogeneity in EGFR-Mutant NSCLC results in divergent resistance mechanisms in response to EGFR tyrosine kinase inhibition. Cancer Res. 75:4372–4383. 2015. View Article : Google Scholar : PubMed/NCBI
9	Ciuffreda L, Incani UC, Steelman LS, Abrams SL, Falcone I, Curatolo AD, Chappell WH, Franklin RA, Vari S, Cognetti F, et al: Signaling intermediates (MAPK and PI3K) as therapeutic targets in NSCLC. Curr Pharm Des. 20:3944–3957. 2014. View Article : Google Scholar : PubMed/NCBI
10	Schrank Z, Chhabra G, Lin L, Iderzorig T, Osude C, Khan N, Kuckovic A, Singh S, Miller RJ and Puri N: Current molecular-targeted therapies in NSCLC and their mechanism of resistance. Cancers (Basel). 10(pii): E2242018. View Article : Google Scholar : PubMed/NCBI
11	Goldstraw P, Ball D, Jett JR, Le Chevalier T, Lim E, Nicholson AG and Shepherd FA: Non-small-cell lung cancer. Lancet. 378:1727–1740. 2011. View Article : Google Scholar : PubMed/NCBI
12	Misra A and Green MR: From polyadenylation to splicing: Dual role for mRNA 3′end formation factors. RNA Biol. 13:259–264. 2016. View Article : Google Scholar : PubMed/NCBI
13	Zhang B, Liu Y, Liu D and Yang L: Targeting cleavage and polyadenylation specific factor 1 via shRNA inhibits cell proliferation in human ovarian cancer. J Biosci. 42:417–425. 2017. View Article : Google Scholar : PubMed/NCBI
14	Nilubol N, Boufraqech M, Zhang L and Kebebew E: Loss of CPSF2 expression is associated with increased thyroid cancer cellular invasion and cancer stem cell population, and more aggressive disease. J Clin Endocrinol Metab. 99:E1173–E1182. 2014. View Article : Google Scholar : PubMed/NCBI
15	Sung TY, Kim M, Kim TY, Kim WG, Park Y, Song DE, Park SY, Kwon H, Choi YM, Jang EK, et al: Negative expression of CPSF2 predicts a poorer clinical outcome in patients with papillary thyroid carcinoma. Thyroid. 25:1020–1025. 2015. View Article : Google Scholar : PubMed/NCBI
16	Yi C, Wang Y, Zhang C, Xuan Y, Zhao S, Liu T, Li W, Liao Y, Feng X, Hao J, et al: Cleavage and polyadenylation specific factor 4 targets NF-κB/cyclooxygenase-2 signaling to promote lung cancer growth and progression. Cancer Lett. 381:1–13. 2016. View Article : Google Scholar : PubMed/NCBI
17	Chen W, Qin L, Wang S, Li M, Shi D, Tian Y, Wang J, Fu L, Li Z, Guo W, et al: CPSF4 activates telomerase reverse transcriptase and predicts poor prognosis in human lung adenocarcinomas. Mol Oncol. 8:704–716. 2014. View Article : Google Scholar : PubMed/NCBI
18	Tang Z, Yu W, Zhang C, Zhao S, Yu Z, Xiao X, Tang R, Xuan Y, Yang W, Hao J, et al: CREB-binding protein regulates lung cancer growth by targeting MAPK and CPSF4 signaling pathway. Mol Oncol. 10:317–329. 2016. View Article : Google Scholar : PubMed/NCBI
19	Chen W, Guo W, Li M, Shi D, Tian Y, Li Z, Wang J, Fu L, Xiao X, Liu QQ, et al: Upregulation of cleavage and polyadenylation specific factor 4 in lung adenocarcinoma and its critical role for cancer cell survival and proliferation. PLoS One. 8:e827282013. View Article : Google Scholar : PubMed/NCBI
20	Appiah-Kubi K, Lan T, Wang Y, Qian H, Wu M, Yao X, Wu Y and Chen Y: Platelet-derived growth factor receptors (PDGFRs) fusion genes involvement in hematological malignancies. Crit Rev Oncol Hematol. 109:20–34. 2017. View Article : Google Scholar : PubMed/NCBI
21	Cancer Genome Atlas Research Network, ; Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C and Stuart JM: The cancer genome atlas Pan-cancer analysis project. Nat Genet. 45:1113–1120. 2013. View Article : Google Scholar : PubMed/NCBI
22	Chang JT, Lee YM and Huang RS: The impact of the Cancer Genome Atlas on lung cancer. Transl Res. 166:568–585. 2015. View Article : Google Scholar : PubMed/NCBI
23	Zhou JD, Wang YX, Zhang TJ, Li XX, Gu Y, Zhang W, Ma JC, Lin J and Qian J: Identification and validation of SRY-box containing gene family member SOX30 methylation as a prognostic and predictive biomarker in myeloid malignancies. Clin Epigenetics. 10:922018. View Article : Google Scholar : PubMed/NCBI
24	Fisler DA, Sikaria D, Yavorski JM, Tu YN and Blanck G: Elucidating feed-forward apoptosis signatures in breast cancer datasets: Higher FOS expression associated with a better outcome. Oncol Lett. 16:2757–2763. 2018.PubMed/NCBI
25	Chen J, Fu G, Chen Y, Zhu G and Wang Z: Gene-expression signature predicts survival benefit from postoperative chemoradiotherapy in head and neck squamous cell carcinoma. Oncol Lett. 16:2565–2578. 2018.PubMed/NCBI
26	Zhu Z, Yu YP, Shi Y, Nelson JB and Luo J: CSR1 induces cell death through inactivation of CPSF3. Oncogene. 28:41–51. 2009. View Article : Google Scholar : PubMed/NCBI
27	Tessema M, Yingling CM, Thomas CL, Klinge DM, Bernauer AM, Liu Y, Dacic S, Siegfried JM, Dahlberg SE, Schiller JH and Belinsky SA: SULF2 methylation is prognostic for lung cancer survival and increases sensitivity to topoisomerase-I inhibitors via induction of ISG15. Oncogene. 31:4107–4116. 2012. View Article : Google Scholar : PubMed/NCBI
28	Carney BJ, Rangachari D, VanderLaan PA, Gowen K, Schrock AB, Ali SM and Costa DB: De novo ERBB2 amplification causing intrinsic resistance to erlotinib in EGFR-L858R mutated TKI-naive lung adenocarcinoma. Lung Cancer. 114:108–110. 2017. View Article : Google Scholar : PubMed/NCBI
29	Gu FF, Zhang Y, Liu YY, Hong XH, Liang JY, Tong F, Yang JS and Liu L: Lung adenocarcinoma harboring concomitant SPTBN1-ALK fusion, c-Met overexpression, and HER-2 amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy. J Hematol Oncol. 9:662016. View Article : Google Scholar : PubMed/NCBI
30	Pu W, Geng X, Chen S, Tan L, Tan Y, Wang A, Lu Z, Guo S, Chen X and Wang J: Aberrant methylation of CDH13 can be a diagnostic biomarker for lung adenocarcinoma. J Cancer. 7:2280–2289. 2016. View Article : Google Scholar : PubMed/NCBI