Proteomic Stratification of Prognosis and Treatment Options for Small Cell Lung Cancer

Small cell lung cancer(SCLC)is a highly malignant and heterogeneous cancer with limited therapeutic options and prognosis prediction models.Here,we analyzed formalin-fixed,paraffin-embedded(FFPE)samples of surgical resections by proteomic profiling,and stratified SCLC into three proteomic subtypes(S-I,S-II,and S-III)with distinct clinical outcomes and chemotherapy responses.The proteomic subtyping was an independent prognostic factor and performed better than current tumor–node–metastasis or Veterans Administration Lung Study Group staging methods.The subtyping results could be further validated using FFPE biopsy samples from an independent cohort,extending the analysis to both surgical and biopsy samples.The signatures of the S-II subtype in particular suggested potential benefits from immunotherapy.Differentially overexpressed proteins in S-III,the worst prognostic subtype,allowed us to nominate potential therapeutic targets,indicating that patient selection may bring new hope for previously failed clinical trials.Finally,analysis of an independent cohort of SCLC patients who had received immunotherapy validated the prediction that the S-II patients had better progression-free survival and overall survival after first-line immunotherapy.Collectively,our study provides the rationale for future clinical investigations to validate the current findings for more accurate prognosis prediction and precise treatments.

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.