Research Article

The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213003, China

Heart & Lung Disease Laboratory, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213003, China

‡Authors contributed equally

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Yongfei Fan‡

The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213003, China

‡Authors contributed equally

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Yifeng Mao

The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213003, China

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Ming Lou

The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213003, China

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Xiaoshuang Liu

Nanjing Jinling Hospital: East Region Military Command General Hospital, Nanjing, Jiangsu, 210002, China

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Kai Yuan

*Author for correspondence:

E-mail Address: yuankai202001@163.com

The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213003, China

Heart & Lung Disease Laboratory, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213003, China

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Jichun Tong

**Author for correspondence:

E-mail Address: tongjichun2021@163.com

https://orcid.org/0000-0002-7882-4398

The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213003, China

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Published Online:24 Feb 2022https://doi.org/10.2217/bmm-2021-1090

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Abstract

Purpose: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. The protein NCAPG plays a significant role in tumor development. Patients & methods: We set up a tissue microarray (containing 140 NSCLC and ten normal lung tissues) and performed immunohistochemistry to assess NCAPG expression in the tissues of 140 patients. The prognostic value of NCAPG in NSCLC was assessed using the univariate and multivariate Cox proportional hazards regression models and Kaplan–Meier plots. We analyzed the association between NCAPG and immune infiltration in NSCLC. Results: Multifactorial analysis and Kaplan–Meier plots revealed that upregulation of NCAPG expression was an independent factor in the prognosis of NSCLC. Data from CIBERSORT showed a negative correlation between NCAPG and the expression of memory CD4⁺ T cells, CD8⁺ T cells, dendritic cells, macrophages, mast cells and natural killer cells (p < 0.001). Gene set enrichment analysis revealed that cell cycle, adhesion and proliferation were significantly enriched in samples with a high NCAPG expression. Conclusion:NCAPG is a novel biomarker of prognosis and is associated with immune cell infiltration in the tumor microenvironment. Thus it may be a potential target in NSCLC treatment.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J. Clin. 67(1), 7–30 (2017). • Indicates that non-small cell lung cancer (NSCLC) has the highest number of lung cancer-related deaths of all cancers in men and women worldwide.
MedlineGoogle Scholar
2. Cao M, Chen W. Epidemiology of lung cancer in China. Thorac. Cancer 10(1), 3–7 (2019).
MedlineGoogle Scholar
3. Blum A, Wang P, Zenklusen JC. SnapShot: TCGA-analyzed tumors. Cell 173(2), 530 (2018).
Medline CASGoogle Scholar
4. Arai T, Okato A, Yamada Y et al. Regulation of NCAPG by miR-99a-3p (passenger strand) inhibits cancer cell aggressiveness and is involved in CRPC. Cancer Med. 7(5), 1988–2002 (2018).
Medline CASGoogle Scholar
5. Dong M, Xu T, Cui X, Li H, Li X, Xia W. NCAPG upregulation mediated by four microRNAs combined with activation of the p53 signaling pathway is a predictor of poor prognosis in patients with breast cancer. Oncol. Lett. 21(4), 323 (2021). •• NCAPG upregulation is a predictor of poor prognosis in NSCLC patients.
Medline CASGoogle Scholar
6. Gong C, Ai J, Fan Y et al. NCAPG promotes the proliferation of hepatocellular carcinoma through PI3K/Akt signaling. Onco Targets Ther. 12, 8537–8552 (2019).
Medline CASGoogle Scholar
7. Xiao C, Gong J, Jie Y et al. NCAPG Is a promising therapeutic target across different tumor types. Front Pharmacol. 11, 387 (2020).
Medline CASGoogle Scholar
8. Jiang L, Ren L, Chen H et al. NCAPG confers trastuzumab resistance via activating SRC/STAT3 signaling pathway in HER2-positive breast cancer. Cell Death Dis. 11(7), 547 (2020).
Medline CASGoogle Scholar
9. Lee SS, Cheah YK. The interplay between microRNAs and cellular components of tumour microenvironment (TME) on non-small-cell lung cancer (NSCLC) progression. J. Immunol. Res. 2019, 3046379 (2019).
MedlineGoogle Scholar
10. Liu Z, Ning Z, Lu H et al. Long non-coding RNA RFPL3S is a novel prognostic biomarker in lung cancer. Oncol Lett. 20(2), 1270–1280 (2020).
Medline CASGoogle Scholar
11. Geng Q, Shen Z, Li L, Zhao J. COL1A1 is a prognostic biomarker and correlated with immune infiltrates in lung cancer. PeerJ 9, e11145 (2021).
MedlineGoogle Scholar
12. Guo ZY, Zhu ZT. NCAPG is a prognostic biomarker associated with vascular invasion in hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 25(23), 7238–7251 (2021).
MedlineGoogle Scholar
13. Sun DP, Lin CC, Hung ST et al. Aberrant expression of NCAPG is associated with prognosis and progression of gastric cancer. Cancer Manag. Res. 12, 7837–7846 (2020). •• Aberrant expression of NCAPG is associated with the prognosis and progression of many cancers.
Medline CASGoogle Scholar
14. Song B, Du J, Song DF, Ren JC, Feng Y. Dysregulation of NCAPG, KNL1, miR-148a-3p, miR-193b-3p, and miR-1179 may contribute to the progression of gastric cancer. Biol. Res. 51(1), 44 (2018).
Medline CASGoogle Scholar
15. Wu Y, Lin Y, Pan J et al. NCAPG promotes the progression of lung adenocarcinoma via the TGF-β signaling pathway. Cancer Cell Int. 21(1), 443 (2021). •• NCAPG is a multifunctional peptide involved in cell proliferation, migration, apoptosis, tumorigenesis and innate immune response.
Medline CASGoogle Scholar
16. Liu C, Yan Y, Di F, Li W, Yin X, Dong L. Inhibition of NCAPG expression inactivates the Wnt/β-catenin signal to suppresses endometrial cancer cell growth in vitro. Environ. Toxicol. 36(12), 2512–2520 (2021).
Medline CASGoogle Scholar
17. Pan JH, Zhou H, Cooper L et al. LAYN is a prognostic biomarker and correlated with immune infiltrates in gastric and colon cancers. Front. Immunol. 10, 6 (2019).
Medline CASGoogle Scholar
18. Shen H, Wang Z, Ren S et al. Prognostic biomarker MITD1 and its correlation with immune infiltrates in hepatocellular carcinoma (HCC). Int. Immunopharmacol. 81, 106222 (2020).
Medline CASGoogle Scholar
19. Zhao R, Peng C, Song C et al. BICC1 as a novel prognostic biomarker in gastric cancer correlating with immune infiltrates. Int. Immunopharmacol. 87, 106828 (2020).
Medline CASGoogle Scholar
20. Chen Q, Pu N, Yin H et al. CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer. J. Cell. Mol. Med. 24(15), 8674–8686 (2020).
Medline CASGoogle Scholar
21. Zhang X, Wang H, Han Y et al. NCAPG induces cell proliferation in cardia adenocarcinoma via PI3K/AKT signaling pathway. Onco Targets Ther. 13, 11315–11326 (2020).
Medline CASGoogle Scholar
22. Xiao Z, Hu L, Yang L et al. TGFβ2 is a prognostic-related biomarker and correlated with immune infiltrates in gastric cancer. J. Cell. Mol. Med. 24(13), 7151–7162 (2020).
Medline CASGoogle Scholar
23. Zhang X, Zhu M, Wang H et al. Overexpression of NCAPG inhibits cardia adenocarcinoma apoptosis and promotes epithelial–mesenchymal transition through the Wnt/β-catenin signaling pathway. Gene 766, 145163 (2021). •• These findings suggested a potential association between NCAPG expression and levels of immune infiltration in NSCLC.
Medline CASGoogle Scholar
24. Guo X, Zhang Y, Zheng L et al. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing. Nat. Med. 24, 978–985 (2018).
Medline CASGoogle Scholar
25. Desmedt C, Salgado R, Fornili M et al. Immune infiltration in invasive lobular breast cancer. J. Natl Cancer Inst. 110(7), 768–776 (2018).
MedlineGoogle Scholar
26. Zhang Q, Su R, Shan C, Gao C, Wu P. Non-SMC condensin I complex, subunit G (NCAPG) is a novel mitotic gene required for hepatocellular cancer cell proliferation and migration. Oncol. Res. 26(2), 269–276 (2018).
MedlineGoogle Scholar
27. Eraso-Pichot A, Brasó-Vives M, Golbano A et al. GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes. Glia 66(8), 1724–1735 (2018).
MedlineGoogle Scholar

Vol. 16, No. 7

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History

Received 12 December 2021

Accepted 8 February 2022

Published online 24 February 2022

Published in print May 2022

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Keywords

Author contributions

This subject and manuscript were designed and written by Y Zhou and Y Fan. Y Zhou completed the experiment. M Lou analyzed data compilation. X Liu and M Yifeng were responsible for the literature search to improve the project, and revised the manuscript. T Jichun and Y Kai were responsible for administrative, technical or material support (building a database). All authors reviewed the manuscript and approved the manuscript for publication.

Acknowledgments

The authors acknowledge the TCGA, GEO, TIMER and CIBERSORT databases for free use.

Financial & competing interests disclosure

The following funds support this work: 333 Project of Jiangsu Province (grant no. BRA2020157); Six One Project, Research Projects of High-level Medical Personnel of Jiangsu Province (grant no. LGY2019025); High-level Talent Selection and Training Project of the 16th Batch of Six Talent Peak in Jiangsu Province (grant no. WSN-245); Medical Scientific Research Foundation of Jiangsu Commission of Health (grant no. H2018083); Jiangsu Provincial Medical Youth Talent (Jiangsu Health Scientific Education 2017 no. 3); 333 High-Level Talent Training Project (grant no. 2016, III-0719); High-Level Medical Talents Training Project (grant no. 2016CZBJ042). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research. All patients or their family members provided written informed consent.

Availability of data & materials

The authors obtained a tissue microarray (HlugC120PT01) from Superbiotek (Shanghai, China), which consisted of 140 non-small-cell lung cancer tissue samples and ten normal lung tissues. All patients had undergone lung cancer resection in 2005. We had access to complete clinical information from all patients (112 men and 28 women).

The data that support the findings of this study are openly available in The Cancer Genome Atlas data portal (https://tcga-data.nci.nih.gov/tcga/), Gene Expression Profiling Interactive Analysis (GEPIA) (http://gepia.cancer-pku.cn/index.html) and the Tumor Immune Estimation Resource (TIMER) database (https://cistrome.shinyapps.io/timer/). The rest of the data are available from the corresponding author on reasonable request.

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NCAPG is a prognostic biomarker of immune infiltration in non-small-cell lung cancer

Abstract

References