Serum semaphorin 4C as a diagnostic biomarker in breast cancer: A multicenter retrospective study

Cancer Communications

article

Ya Wang¹  Long Qiao⁴  Jie Yang¹  Xiong Li⁵  Yaqi Duan⁶  Jiahao Liu¹  Shaoqi Chen⁷  Huayi Li²  Dan Liu¹  Tian Fang²  Jingjing Ma¹  Xiaoting Li¹  Fei Ye⁸  Junxiang Wan⁹  Juncheng Wei¹  Qin Xu¹  Ensong Guo¹  Ping Jin²  Mingfu Wu¹  Lin Zhang^1,10  Yun Xia^1,10  Yaqun Wu^1,10  Jun Shao^1,11  Yaojun Feng^1,11  Qing Zhang^1,12  Zongyuan Yang¹  Gang Chen¹  Qinghua Zhang⁵  Xingrui Li^1,10  Shixuan Wang¹  Junbo Hu²  Xiaoyun Wang^1,13  Mona P. Tan^1,14  Kazuaki Takabe^1,15  Beihua Kong^1,12  Qifeng Yang^1,16  Ding Ma¹  Qinglei Gao¹ 

[1] Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;Cancer Biology Research Center ,(Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;These authors contributed equally to this work;Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University;Department of Gynecology and Obstetrics, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology;Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;Department of Obstetrics and Gynecology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology;Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;Leonard Davis School of Gerontology, University of Southern California;Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;Department of Breast Surgery, Hubei Cancer Hospital;Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University;Yidu Cloud;MammoCare, The Breast Clinic & Surgery;Department of Surgery and the Massey Cancer Centre, Virginia Commonwealth University School of Medicine;Department of Breast Surgery, Qilu Hospital of Shandong University

关键词: breast cancer;    semaphorin 4C;    serum biomarker;    diagnosis;    early detection;    ductal carcinoma in situ;    pan-cancer analysis;    enzyme-linked immunosorbent assay;   

DOI  :  10.1002/cac2.12233

学科分类：社会科学、人文和艺术（综合）

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY|CC BY-NC-ND