{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T12:05:10Z","timestamp":1773835510238,"version":"3.50.1"},"reference-count":43,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"12","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Science and Technology Major Sub\u2010Project","award":["2018ZX10301402\u2010002"],"award-info":[{"award-number":["2018ZX10301402\u2010002"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772787"],"award-info":[{"award-number":["81772787"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81902653"],"award-info":[{"award-number":["81902653"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072889"],"award-info":[{"award-number":["82072889"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2019kfyXMBZ024"],"award-info":[{"award-number":["2019kfyXMBZ024"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Commun"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">To date, there is no approved blood\u2010based 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      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\u2010cancer 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\u2010treatment serum SEMA4C levels, measured using optimized\n                      <jats:italic toggle=\"yes\">in\u2010house<\/jats:italic>\n                      enzyme\u2010linked 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\u2010surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification. There was no restriction on disease stage for eligibilities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      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 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001). Elevated serum SEMA4C levels had AUC of 0.920 (95% confidence interval [CI]: 0.900\u20130.941) and 0.932 (95%CI: 0.911\u20130.953) for breast cancer detection in the two validation cohorts. The AUCs for detecting early\u2010stage breast cancer (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 366) and ductal carcinoma in situ (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 85) were 0.931 (95%CI: 0.916\u20130.946) and 0.879 (95%CI: 0.832\u20130.925), respectively. Serum SEMA4C levels significantly decreased after surgery, and the reduction was more striking after modified radical mastectomy, compared with mass excision (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cac2.12233","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T03:42:51Z","timestamp":1636083771000},"page":"1373-1386","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Serum semaphorin 4C as a diagnostic biomarker in breast cancer: A multicenter retrospective study"],"prefix":"10.34133","volume":"41","author":[{"given":"Ya","family":"Wang","sequence":"first","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Qiao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, P. R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiong","family":"Li","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaqi","family":"Duan","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahao","family":"Liu","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huayi","family":"Li","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. 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China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Ye","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junxiang","family":"Wan","sequence":"additional","affiliation":[{"name":"University of Southern California","place":["Los Angeles, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juncheng","family":"Wei","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Xu","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, P. R. 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China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"issue":"6","key":"e_1_3_2_2_2","first-page":"438","article-title":"Breast cancer statistics, 2019","volume":"69","author":"DeSantis CE","year":"2019","unstructured":"DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, et\u00a0al. Breast cancer statistics, 2019. 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Cancer Commun (Lond). 2020;40((8)):329\u201044.","journal-title":"Cancer Commun (Lond)"},{"issue":"15","key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1001\/jama.2015.12783","article-title":"Breast cancer screening for women at average risk: 2015 guideline update from the American Cancer Society","volume":"314","author":"Oeffinger KC","year":"2015","unstructured":"Oeffinger KC, Fontham ET, Etzioni R, Herzig A, Michaelson JS, Shih YC, et\u00a0al. Breast cancer screening for women at average risk: 2015 guideline update from the American Cancer Society. 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