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

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 pretreatment serum SEMA4C levels,measured using optimized in-house enzymelinked 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.

A 10-miRNA risk score-based prediction model for pathological complete response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer

Patients with hormone receptor(HR)-positive tumors breast cancer usually experience a relatively low pathological complete response(p CR)to neoadjuvant chemotherapy(NAC).Here,we derived a 10-micro RNA risk score(10-mi RNA RS)-based model with better performance in the prediction of p CR and validated its relation with the disease-free survival(DFS)in 755 HRpositive breast cancer patients(273,265,and 217 in the training,internal,and external validation sets,respectively).This model,presented as a nomogram,included four parameters:the 10-mi RNA RS found in our previous study,progesterone receptor(PR),human epidermal growth factor receptor 2(HER2)status,and volume transfer constant(K).Favorable calibration and discrimination of 10-mi RNA RS-based model with areas under the curve(AUC)of 0.865,0.811,and 0.804 were shown in the training,internal,and external validation sets,respectively.Patients who have higher nomogram score(>92.2)with NAC treatment would have longer DFS(hazard ratio=0.57;95%CI:0.39–0.83;P=0.004).In summary,our data showed the 10-mi RNA RS-based model could precisely identify more patients who can attain p CR to NAC,which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HRpositive breast cancer.