Introduction Platinum resistance seriously affects the survival of patients with epithelial ovarian cancer (EOC). Extracellular matrix play an important role in platinum resistance. Lumican (LUM) is an important proteoglycan in extracellular matrix. We intended to explore the expression of LUM in EOC and its effect on platinum resistance.

Methods Expression profile microarray was used to explore the mechanism of platinum resistance. Immunofluorescence and qRT-PCR was used to detect the expression of LUM in drug-resistant (SKOV3DDP) and wild-type (SKOV3) cells. LUM was detected by immunohistochemistry in tissues. After establishing LUM-overexpressing cells ( SKOV3 LUM-OE) and knocked-out LUM cells (SKOV3DDP LUM-KO), the effects of LUM were evaluated. CCK8 was performed to evaluate the effects of cisplatin on EOC cells. Immunofluorescence, western blot and qRT-PCR were performed for determining TGFB1, CDH1, CDH2, ZEB1 and MMP9.

Results The expression of extracellular matrix related genes was significantly enriched in platinum-resistant tissue. The expression of LUM in SKOV3DDP was significantly higher than that in SKOV3, and it was significantly increased after cisplatin treatment of SKOV3. LUM was significantly overexpressed in platinum-resistant tissues (77.78% vs 32.0%, P<0.001), and it’s an independent prognostic factor for platinum resistance (OR=8.11, P=0.002). The changes of cisplatin sensitivity were consistent with the changes of LUM after overexpression or knockout it. TGFB1 was positively correlated with LUM expression. CDH2, MMP9, ZEB1 were strongly induced and CDH1 was suppresed in SKOV3 LUM-OE.

Conclusion/Implications High expression of LUM is associated with platinum resistance and poor prognosis in EOC. LUM activates TGF-β-EMT signaling pathway to promote platinum resistance in EOC.