Abstract

Background

To date, there is no approved blood‐based biomarker for breast cancer detection. Herein, we aimed to assess semaphorin 4C (SEMA4C), a pivotal protein involved in breast cancer progression, as a serum diagnostic biomarker.

Methods

We included 6,213 consecutive inpatients from Tongji Hospital, Qilu Hospital, and Hubei Cancer Hospital. Training cohort and two validation cohorts were introduced for diagnostic exploration and validation. A pan‐cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors. Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed. We hypothesized that increased pre‐treatment serum SEMA4C levels, measured using optimized in‐house enzyme‐linked immunosorbent assay kits, could detect breast cancer. The endpoints were diagnostic performance, including area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Post‐surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification. There was no restriction on disease stage for eligibilities.

Results

We included 2667 inpatients with breast lesions, 2378 patients with other solid tumors, and 1168 healthy participants. Specifically, 118 patients with breast cancer were diagnosed with stage 0 (5.71%), 620 with stage I (30.00%), 966 with stage II (46.73%), 217 with stage III (10.50%), and 8 with stage IV (0.39%). Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls (P < 0.001). Elevated serum SEMA4C levels had AUC of 0.920 (95% confidence interval [CI]: 0.900–0.941) and 0.932 (95%CI: 0.911–0.953) for breast cancer detection in the two validation cohorts. The AUCs for detecting early‐stage breast cancer (n = 366) and ductal carcinoma in situ (n = 85) were 0.931 (95%CI: 0.916–0.946) and 0.879 (95%CI: 0.832–0.925), respectively. Serum SEMA4C levels significantly decreased after surgery, and the reduction was more striking after modified radical mastectomy, compared with mass excision (P < 0.001). The positive rate of enhanced serum SEMA4C levels was 84.77% for breast cancer and below 20.75% for the other 14 solid tumors.

Conclusions

Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis. However, validation in prospective settings and by other study groups is warranted.

Details

Title
Serum semaphorin 4C as a diagnostic biomarker in breast cancer: A multicenter retrospective study
Author
Wang, Ya 1 ; Long, Qiao 2 ; Yang, Jie 1 ; Li, Xiong 3 ; Duan, Yaqi 4 ; Liu, Jiahao 1 ; Chen, Shaoqi 5 ; Li, Huayi 6 ; Liu, Dan 1 ; Tian Fang 6 ; Ma, Jingjing 1 ; Li, Xiaoting 1 ; Ye, Fei 7 ; Wan, Junxiang 8 ; Wei, Juncheng 1 ; Xu, Qin 1 ; Guo, Ensong 1 ; Jin, Ping 6 ; Wu, Mingfu 1 ; Zhang, Lin 9 ; Xia, Yun 9 ; Wu, Yaqun 9 ; Shao, Jun 10 ; Feng, Yaojun 10 ; Zhang, Qing 11 ; Yang, Zongyuan 1 ; Chen, Gang 1 ; Zhang, Qinghua 3 ; Li, Xingrui 9 ; Wang, Shixuan 1 ; Hu, Junbo 6 ; Wang, Xiaoyun 12 ; Tan, Mona P 13 ; Takabe, Kazuaki 14 ; Kong, Beihua 11 ; Yang, Qifeng 15 ; Ding, Ma 1 ; Gao, Qinglei 1   VIAFID ORCID Logo 

1  Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China 
2  Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China 
3  Department of Gynecology and Obstetrics, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China 
4  Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China 
5  Department of Obstetrics and Gynecology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China 
6  Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China 
7  Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China 
8  Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA 
9  Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China 
10  Department of Breast Surgery, Hubei Cancer Hospital, Wuhan, Hubei, P. R. China 
11  Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China 
12  Yidu Cloud (Beijing) Technology Co., Beijing, P. R. China 
13  MammoCare, The Breast Clinic & Surgery, Singapore, Singapore 
14  Department of Surgery and the Massey Cancer Centre, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA 
15  Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China 
Pages
1373-1386
Section
ORIGINAL ARTICLES
Publication year
2021
Publication date
Dec 2021
Publisher
John Wiley & Sons, Inc.
e-ISSN
2523-3548
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1002/cac2.12233
ProQuest document ID
2612610554
Copyright
© 2021. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.