Diagnosis Value of SEMA4C in Breast Cancer

Breast cancer remains the most common cancer in women worldwide. Early diagnosis can greatly improve the prognosis. To date, imaging examination is still the most important diagnostic and grading tool for breast cancer. Semaphorin4C (SEMA4C) has previously been identified as a highly expressed protein by breast cancer-associated lymphatic endothelial cells (LECs). The study is undertaken to evaluate the diagnostic efficiency of SEMA4C.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Neoplasm Female
• Intervention / Treatment: Diagnostic test: Breast cancer group; Diagnostic test: Benign breast tumor group

Detailed Description

Breast cancer remains the most common cancer in women worldwide, with approximately 1.68 million new cases, and 0.52 million deaths, annually. Meanwhile the incidence of breast cancer continues to increase. Early diagnosis and access to optimum treatment are crucial to reduce mortality associated with breast cancer. Currently, mammography and breast ultrasonography are essential for the detection and diagnosis of disease, and breast magnetic resonance imaging is the choice to estimate the extent of disease and guide appropriate treatment. However, there is no robust biomarkers for early detection of breast cancer.

Semaphorin4C (SEMA4C) has been previously identified as a highly expressed protein by breast cancer-associated lymphatic endothelial cells (LECs) using in situ laser capture microdissection of lymphatic vessels, followed by cDNA microarray analysis. Moreover, membrane-bound SEMA4C is cleaved by matrix metalloproteinase (MMPs) to release a soluble form of this protein. Therefore, this prospective project aims to assess the early diagnostic value of SEMA4C as a biomarker for breast cancer.

• Study Type: Observational
• Enrollment (Anticipated): 2300

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Participants including patients with benign breast tumors and patients with breast cancer. All cases were confirmed histopathologically according to the WHO Classification of Tumors.

Description

Inclusion Criteria:

• Receiving no treatment before diagnosis
• Establishing Diagnosis according to biopsy or surgery

Exclusion Criteria:

• Patients who are not mentally capable of giving written informed consent
• Clinical data missing
• Serum samples doesn't qualified
• Patients with a diagnosis of other severe acute or chronic medical conditions that may interfere with the interpretation of the study results

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Breast cancer group; Patients who have histologically confirmed new diagnosis of breast cancer are recruited.	Diagnostic test: Breast cancer group; All the serum samples are collected before any treatments and will be tested in single center in order to decrease bias. Serum SEMA4C levels were measured using a double antibody sandwich ELISA method using in-house SEMA4C detection kits.
Benign breast tumor group; Patients who have histologically confirmed new diagnosis of benign breast tumors are recruited.	Diagnostic test: Benign breast tumor group; All the serum samples are collected before any treatments and will be tested in single center in order to decrease bias. Serum SEMA4C levels were measured using a double antibody sandwich ELISA method using in-house SEMA4C detection kits.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic potential of SEMA4C as a biomarker for breast cancer	Analyzing the predictive value of SEMA4C in the diagnosis of breast cancer.	At the time of inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum SEMA4C, Mammography, breast US and MRI in comparison and combination to distinguish breast cancer from benign breast tumor	Compare and combine the diagnostic performances of Serum SEMA4C, traditional mammography, ultrasonography, and contrast-enhanced MR imaging in the assessment of breast cancer	At the time of inclusion

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Qilu Hospital of Shandong University; Hubei Cancer Hospital; The First People's Hospital of Jingzhou; Wuhan Central Hospital; Xiangyang Central Hospital

Publications and helpful links

General Publications

• Wei JC, Yang J, Liu D, Wu MF, Qiao L, Wang JN, Ma QF, Zeng Z, Ye SM, Guo ES, Jiang XF, You LY, Chen Y, Zhou L, Huang XY, Zhu T, Meng L, Zhou JF, Feng ZH, Ma D, Gao QL. Tumor-associated Lymphatic Endothelial Cells Promote Lymphatic Metastasis By Highly Expressing and Secreting SEMA4C. Clin Cancer Res. 2017 Jan 1;23(1):214-224. doi: 10.1158/1078-0432.CCR-16-0741. Epub 2016 Jul 8.
• Gurrapu S, Pupo E, Franzolin G, Lanzetti L, Tamagnone L. Sema4C/PlexinB2 signaling controls breast cancer cell growth, hormonal dependence and tumorigenic potential. Cell Death Differ. 2018 Jul;25(7):1259-1275. doi: 10.1038/s41418-018-0097-4. Epub 2018 Mar 19.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2023
• Primary Completion (ANTICIPATED): September 1, 2023
• Study Completion (ANTICIPATED): September 1, 2024

Study Registration Dates

• First Submitted: September 3, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (ACTUAL): September 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 20, 2022
• Last Update Submitted That Met QC Criteria: October 18, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 2018-TJ-BCD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No