ORIGINAL ARTICLE

Open Access

Biglycan, tumor endothelial cell secreting proteoglycan, as possible biomarker for lung cancer

Hirofumi Morimoto

Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan

Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan

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Yasuhiro Hida,

Yasuhiro Hida

orcid.org/0000-0003-1759-4215

Department of Cardiovascular and Thoracic Surgery, Hokkaido University Faculty of Medicine, Sapporo, Japan

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Nako Maishi,

Nako Maishi

Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan

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Hiroshi Nishihara,

Hiroshi Nishihara

Genomics Unit, Keio Cancer Center, Keio University School of Medicine, Tokyo, Japan

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Yutaka Hatanaka,

Yutaka Hatanaka

Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan

Research Division of Genome Companion Diagnostics, Hokkaido University Hospital, Sapporo, Japan

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Cong Li,

Cong Li

Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan

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Yoshihiro Matsuno,

Yoshihiro Matsuno

Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan

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Toru Nakamura,

Toru Nakamura

Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan

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Satoshi Hirano,

Satoshi Hirano

Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan

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Kyoko Hida,

Corresponding Author

Kyoko Hida

[email protected]

orcid.org/0000-0002-7968-6062

Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan

Correspondence

Kyoko Hida, Department of Vascular Biology and Molecular Pathology Graduate School of Dental Medicine, Hokkaido University Kita-13, Nishi-7, Kita-Ku, Sapporo, Hokkaido 060-8586, Japan.

Email: [email protected]

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Hirofumi Morimoto,

Hirofumi Morimoto

Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan

Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan

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Yasuhiro Hida,

Yasuhiro Hida

orcid.org/0000-0003-1759-4215

Department of Cardiovascular and Thoracic Surgery, Hokkaido University Faculty of Medicine, Sapporo, Japan

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Nako Maishi,

Nako Maishi

Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan

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Hiroshi Nishihara,

Hiroshi Nishihara

Genomics Unit, Keio Cancer Center, Keio University School of Medicine, Tokyo, Japan

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Yutaka Hatanaka,

Yutaka Hatanaka

Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan

Research Division of Genome Companion Diagnostics, Hokkaido University Hospital, Sapporo, Japan

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Cong Li,

Cong Li

Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan

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Yoshihiro Matsuno,

Yoshihiro Matsuno

Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan

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Toru Nakamura,

Toru Nakamura

Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan

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Satoshi Hirano,

Satoshi Hirano

Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan

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Kyoko Hida,

Corresponding Author

Kyoko Hida

[email protected]

orcid.org/0000-0002-7968-6062

Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan

Correspondence

Kyoko Hida, Department of Vascular Biology and Molecular Pathology Graduate School of Dental Medicine, Hokkaido University Kita-13, Nishi-7, Kita-Ku, Sapporo, Hokkaido 060-8586, Japan.

Email: [email protected]

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First published: 11 March 2021

https://doi.org/10.1111/1759-7714.13907

Citations: 22

Funding information: Grants from Japan Agency for Medical Research and Development, Grant/Award Numbers: JP18ck0106198h0003, JP19ck0106406h0002; JSPS Grants-in-Aid for Scientific Research, Grant/Award Numbers: JP18H02891, JP18K09715; Japan Society for the Promotion of Science

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Abstract

Objectives

In lung cancer, surgery remains the most curative treatment and limited resection is beneficial for patients with low cardiopulmonary function and low malignancy tumors. However, there are no biomarkers of low malignancy to select candidates for limited resection without compromising the outcome of treatments. Recently we identified biglycan (BGN) as a tumor endothelial cell (TEC) marker that is associated with tumor progression in various cancers. In this study, we analyzed the association between BGN expression in TECs in lung cancer and cancer progression in patients.

Materials and Methods

First, we performed immunohistochemistry of BGN with resected lung tumor tissues of 155 patients who had undergone thoracic surgery and analyzed the correlation between BGN-positive vessel density in primary lung tumors and clinicopathological factors. Second, we measured the BGN levels in preoperative serum of other 46 patients with lung cancer by ELISA, and analyzed the correlation between BGN expression in tumor tissues and blood BGN levels.

Results

High BGN expression in the TECs was significantly associated with T factor, and was a significant negative predictor. BGN levels in preoperative serum of 46 patients with lung cancer was significantly correlated with BGN expression in the TECs. Preoperative serum BGN level was significantly lower in healthy volunteers and less invasive adenocarcinoma than in invasive adenocarcinoma and other lung carcinomas. These results suggest that low BGN level in preoperative serum in patients with lung cancer might indicate low malignancy.

Conclusions

BGN can be a potential biomarker for lung cancer.

CONFLICTS OF INTEREST

The authors have no financial conflicts of interest to disclose concerning the study.

Supporting Information

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Citing Literature

Volume12, Issue9

May 2021

Pages 1347-1357

Filename	Description
tca13907-sup-0001-FigureS1.pdfPDF document, 65.1 KB	Supporting Information Figure S1 The expression and survival analysis of biglycan (BGN) in databases. (a) The expression of BGN was compared between 226 lung adenocarcinoma and 20 normal lung tissue samples in the Oncominedatabase. (b) Overall survival analysis of BGN in lung cancer samples in the ICGC database. p value = 0.01328, log-rank test = 6.131
tca13907-sup-0002-TableS1.xlsxExcel 2007 spreadsheet , 12.1 KB	Supporting Information Table S1 Univariate and multivariate analysis for relapse-free survival in 155 patients with lung cancer
tca13907-sup-0003-TableS2.xlsxExcel 2007 spreadsheet , 12.2 KB	Supporting Information Table S2 Univariate and multivariate analysis for overall survival in 155 patients with lung cancer
tca13907-sup-0004-TableS3.xlsxExcel 2007 spreadsheet , 11.6 KB	Supporting Information Table S3 Clinicopathological variates in 46 patients according to biglycan level in preoperative

Biglycan, tumor endothelial cell secreting proteoglycan, as possible biomarker for lung cancer

Abstract

Objectives

Materials and Methods

Results

Conclusions

CONFLICTS OF INTEREST

Supporting Information

REFERENCES

Citing Literature

Figures

References

Information

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Biglycan, tumor endothelial cell secreting proteoglycan, as possible biomarker for lung cancer

Abstract

Objectives

Materials and Methods

Results

Conclusions

CONFLICTS OF INTEREST

Supporting Information

REFERENCES

Citing Literature

Figures

References

Related

Information