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.

HPV-CCDC106 integration alters local chromosome architecture and hijacks an enhancer by three-dimensional genome structure remodeling in cervical cancer

Integration of human papillomavirus(HPV)DNA into the human genome is a reputed key driver of cervical cancer.However,the effects of HPV integration on chromatin structural organization and gene expression are largely unknown.We studied a cohort of 61 samples and identified an integration hot spot in the CCDC106 gene on chromosome 19.We then selected fresh cancer tissue that contained the unique integration loci at CCDC106 with no HPV episomal DNA and performed whole-genome,RNA,chromatin immunoprecipitation and high-throughput chromosome conformation capture(Hi-C)sequencing to identify the mechanisms of HPV integration in cervical carcinogenesis.Molecular analyses indicated that chromosome 19 exhibited significant genomic variation and differential expression densities,with correlation found between three-dimensional(3D)structural change and gene expression.Importantly,HPV integration divided one topologically associated domain(TAD)into two smaller TADs and hijacked an enhancer from PEG3 to CCDC106,with a decrease in PEG3 expression and an increase in CCDC106 expression.This expression dysregulation was further confirmed using 10 samples from our cohort,which exhibited the same HPV-CCDC106 integration.In summary,we found that HPV-CCDC106 integration altered local chromosome architecture and hijacked an enhancer via 3D genome structure remodeling.Thus,this study provides insight into the 3D structural mechanism underlying HPV integration in cervical carcinogenesis.

On De Giorgi's conjecture: Recent progress and open problems

In 1979,De Giorgi conjectured that the only bounded monotone solutions to the Allen-Cahn equation △u+u-u^3=0 in R^N,are one-dimensional.This conjecture and its connection with minimal surfaces and Toda systems are the subject of this survey article.

Catenoidal Layers for the Allen-Cahn Equation in Bounded Domains

This paper presents a new family of solutions to the singularly perturbed Allen-Cahn equation α~2Δu + u(1- u^2) = 0 in a smooth bounded domain Ω R^3, with Neumann boundary condition and α > 0 a small parameter. These solutions have the property that as α→ 0, their level sets collapse onto a bounded portion of a complete embedded minimal surface with finite total curvature intersecting ?Ω orthogonally and that is non-degenerate respect to ?Ω. The authors provide explicit examples of surfaces to which the result applies.

Classification of Positive Ground State Solutions with Different Morse Indices for Nonlinear N-Coupled Schrödinger System

In this paper,we study the following N-coupled nonlinear Schrodinger system■,wheren≤3,N≥3,uj>0,βi,j=βj,i>0 are constants andβj,j=μj,j=1,...,N.There have been intensive studies for the system on existence/non-existence and clas-sification of ground state solutions when N=2.However fewer results about the classification of ground state solution are available for N≥3.In this paper,we first give a complete classification result on ground state solutions with Morse indices 1,2 or 3 for three-coupled Schrodinger system.Then we generalize our results to N-coupled Schrodinger system for ground state solutions with Morse indices 1 and N.We show that any positive ground state solutions with Morse index 1 or Morse index N must be the form of(d1w,d2w,...,dNw)under suitable conditions,where w is the unique positive ground state solution of certain equation.Finally,we generalize our results to fractional N-coupled Schrödinger system.

四、六维的Lin-Ni猜想

本文对于四、六维任意区域的Lin-Ni猜想给出一个非常数解的反例,这里对于区域的对称性、几何以及拓扑性质不作任何假定.