The expression and clinical pathological characteristics,immune cell infiltration,and prognostic significance of TMED2 and Siglec15 in cutaneous malignant melanoma
Wang Rui
Zhang Li
Wei Jianming
Wang Xiaobo
Chen Lu
Zhao Jiaojiao
Li Yu
Abstract：Objective To study the expression of transmembrane p24 trafficking protein 2(TMED2)and sialic acid-binding immunoglobulin-type lectins 15(Siglec15)in cutaneous malignant melanoma(CMM)and their clinicopathological features,immune cell infiltration,and prognostic significance.Methods A total of 109 patients with CMM admitted to the Department of Dermatology,the Fifth Medical Center of Chinese PLA General Hospital from April 2019 to April 2022 were selected as the research subjects.The protein and mRNA expressions of TMED2 and Siglecl5 in CMM tissues were detected by immunohistochemical staining and quantitative real-time PCR(qPCR).R language was used to analyze the relationship be-tween TMED2,Siglec15 expression and immune cell infiltration in the TCGA database.Kaplan-Meier survival analysis and Cox multivariate regression analysis were used to evaluate the effect of TMED2 and Siglec15 protein expression on the prog-nosis of CMM patients.Results The positive rates of TMED2 and Siglec15 in cancer tissues were 67.89％(74/109)and 64.22％(70/109),respectively,which were significantly higher than those in adjacent tissues[7.34％(8/109)and 9.17％(10/109)](x2/P=85.151/＜0.001,71.087/＜0.001).The mRNA expression levels of TMED2 and Siglecl5 in CMM cancer tissues were 2.52±0.54 and 3.03±0.46,respectively,which were significantly higher than those in adjacent tissues(0.93±0.25 and 1.05±0.28)(t/P=27.896/＜0.001,38.387/＜0.001).Analysis of TCGA database showed that TMED2 expression in CMM tissues was positively correlated with Treg cells,macrophages,and neutrophils(r/P=0.310/＜0.001,0.254/＜0.001,0.226/＜0.001),and negatively correlated with CD56+NK cells,CD8+T cells,and NK cells(r/P=-0.407/＜0.001,-0.344/＜0.001,-0.298/＜0.001).Siglec15 expression was positively correlated with Treg cells,macrophages,and follicular helper T cells(TFH)(r/P=0.433/＜0.001,0.488/＜0.001,0.416/＜0.001).The positive rates of TMED2 and Siglec15 in CMM tissues were significantly higher in patients with clinical stage ⅢA-B and lymph node metastasis(x2/P=11.957/0.001,10.366/0.001;12.789/＜0.001,17.217/＜0.001).The 3-year overall survival rate of the TMED2-positive group was 68.92％(51/74),which was significantly lower than that of the negative group(85.71％,30/35)(Log-rank x2=3.320,P＜0.001).The 3-year overall survival rate of the Siglec15-positive group was 67.14％(47/70),which was significantly lower than that of the negative group(87.18％,34/39)(Log-rank x2=5.580,P＜0.001).Clinical stage ⅢA-B,lymph node metastasis,TMED2 positivity,and Siglec15 positivity were inde-pendent risk factors affecting the prognosis of CMM patients[HR(95％CI)=1.665(1.145-2.421),1.383(1.101-1.736),1.508(1.192-1.908),1.391(1.139-1.699)].Conclusion The elevated expression of TMED2 and Siglec15 in CMM is associated with tumor immune infiltration and adverse clinicopathological features,and they represent novel biomarkers for evaluating the prognosis of CMM.
Keywords：Cutaneous malignant melanomaTransmembrane p24 trafficking protein 2Sialic acid-binding immuno-globulin-type lectins 15Immune infiltrationPrognosis
Publication Date：2026-03-18
Online Publishing Date：2026-04-08(First online date of this platform, not the publication date of the document)
Pages：6( 341-346 )