Overexpression of placenta specific 8 is associated with malignant progression and poor prognosis of clear cell renal cell carcinoma.

Background: Placenta specific 8 (PLAC8) plays an important role in many different cellular processes and human diseases, including multiple types of cancer. However, the functional role of PLAC8 in clear cell renal cell carcinoma (ccRCC) has never been elucidated.

Methods: PLAC8 mRNA expression was investigated in 31 pairs of fresh ccRCC tumor tissues and matched adjacent non-tumor tissues by RT-qPCR and confirmed by analyzing the TCGA KRCC dataset which contains RNA-seq data of 534 ccRCC and 72 solid normal tissues. Protein level of PLAC8 expression was also investigated using immunohistochemistry in 129 ccRCC samples. Correlations with clinicopathological factors and overall survival were analyzed. To examine its effect on the biological activity, PLAC8 siRNAs were transfected into ccRCC cells. Cell proliferation was assessed by CCK8 cell viability assays, clone formation assays, and EdU incorporation assays. Cell invasion was examined using transwell assays. RNA sequencing was then performed to further elucidate the mechanisms by which PLAC8 regulates the cancer.

Results: PLAC8 expression was positively correlated with tumor size, metastasis, and clinical stage of ccRCC. Additionally, high PLAC8 expression was closely associated with a shorter overall survival time. Knockdown of PLAC8 with siRNAs significantly reduced the proliferation and invasion of RCC cells and increased the sensitivity of RCC cells to cisplatin. RNA-seq analysis revealed that knockdown of PLAC8 down-regulated the expression of a panel of inflammatory mediators, which suggested that PLAC8 is associated with the ccRCC inflammatory microenvironment. Patients with high expression of PLAC8 had a significantly higher number of infiltrative lymphocytes than patients with low expression of PLAC8.

Conclusion: Our findings suggest that PLAC8 may be a potential prognostic indicator and therapeutic target for ccRCC.