皮肤黑色素瘤中MMRN2高表达促进肿瘤细胞的侵袭和迁移并与不良预后相关

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Overexpression of multimerin-2 promotes cutaneous melanoma cell invasion and migration and is associated with poor prognosis

PANG Jinlong2，ZHAOXinli，ZHANGZhen²，WANGHaojie²，ZHOUXingqi²，YANGYumei²，LIShanshan²，CHANG Xiaoqiang²，LIFeng1²，LIXian1，2

Schoolfclitylhtel 233030， China

Abstract： Objective Toinvestigatetheinhbitoryefectofmultimerin-2（MMRN2）overexpressonongrowthandmetastasisof cutaneous melanoma cells.Methods Clinical data of patients withcutaneous melanoma wereobtained fromthe GEOdatabase tocompareMMRN2expressionsbetweennormalandtumortisses.Aprotein-proteininteractionnetworkwasconstructed usingtheSTRING database，and the intersecting genes from GEPIA2.0were subjected toGOand KEGG enrichmentanalysis. TheprognosticrelevanceofMMRN2expressonlevel wasassessedusing Coxregressionand"timeROC".Thecorrelationsof MMRN2 expresion level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and thessGSEAagorit.olonyforingssayanswellsayndwoundeaingssyereuedtoxainethgesin proliferationand migrationof cultured cutaneous melanoma cels following MMRN2 knockdown. In amouse modelbearing cutaneous melanoma xenograft，theeffectofMMRN2knockdownonvitalorganpathologies，survivalof themiceand GMCSF， CXCL9，andTGF-β1 protein expressions were analyzed. Results MMRN2 was significantly upregulated in metastatic cutaneous melanoma （P<0.001） . Protein interaction network analysis identified 15 intersecting genes，which were enriched in endothelium development andcell-celljunctions.Inpatientswithcutaneousmelanoma，ahighMMRN2 expresion was correlatedwithapoor prognosis，anadvancedTstage，agreaterBreslowdepth，andulceration （P<0.05） .MMRN2 expression level was strongly correlated with 24 immune cell types （P<0.001） ， fibroblasts， endothelial cells，and expressionsofthepro angiogenic genes （KCNJ8， SLCO2A1， NRP1， and COL3A1; P<0.001 ）.In cultured B16F10 cells，MMRN2 knockdown significantly suppressed cell proliferation， migration and invasion and causedremo-delingof the immunosuppressivemicroenvironment.Conclusion MMRN2 overexpression drives progression of cutaneous melanoma byenhancingtumormetastasis，angiogenesis and immune evasion， highlighting its potential as a therapeutic target for melanomas.

Keywords： MMRN2; melanoma; prognosis; bioinformatics;immuneinfiltration

皮肤黑色素瘤（SKCM是一种恶性程度极高的皮肤癌，其发病率和死亡率逐年上升，已成为全球公共卫生领域的重大威胁。（剩余16863字）