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

  • Urology - Original Paper
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Abstract

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.

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Funding

This study was funded by The National Key Research and Development Program of China (No. 2016YFC1305700), and Major Research Fund for the People’s Livelihood of Guangzhou Science and Technology Plan (No. 2011Y-00003).

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Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, China

    Liping Shi, Long Xiao, Baoli Heng, Shijie Mo, Weijun Chen & Zexuan Su

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  1. Liping Shi
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  2. Long Xiao
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Correspondence to Zexuan Su.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Shi, L., Xiao, L., Heng, B. et al. Overexpression of placenta specific 8 is associated with malignant progression and poor prognosis of clear cell renal cell carcinoma. Int Urol Nephrol 49, 1165–1176 (2017). https://doi.org/10.1007/s11255-017-1578-y

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  • DOI: https://doi.org/10.1007/s11255-017-1578-y

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