Presentation Authors: kai yao*, Dong Chen, Xing-liang Tan, Qiang-hua Zhou, Fang-jian Zhou, Guang zhou, China, People's Republic of
Introduction: Metastatic penile squamous cell carcinoma (mPSCC) is associated with poor survival due to the molecular mechanism of proliferation and metastasis stay unclear. For this reason,we have performed the whole-genome microarrays analysis in 12 mPSCC patients with matched primary,metastasis and normal pairs to explore the expression difference in this rare malignancy.
Methods: A total of 36 clinically matched specimens are divided into normal tissue group (N), penile primary carcinoma group (PCA) and lymph node metastasis group (LM) respectively. After eliminating the non-compliant paired samples owing to RNA degradation,we have performed comprehensive genome microarrays by Affymetirx and establish a mPSCC gene expression model. Each gene expression is detected by the illuminated intensity of the probe and calculate the value of fold changes(FC) between two groups(PCA vs N group and LM vs N group). FC>2 and false discover rate < 0.05 is the screening criteria in gene with distinctive expression.Genes with higher expression levels in M than PCA are verified by RT-qPCR and HCS cell proliferation screening experiments. Lastly, the potential genes which have an radical influence on proliferation or metastasis are validated by in vivo and in vitro experiments.
Results: 8 in 12 mPSCC patientsâ€™ paired samples with high quality used to establish the whole-genome expression model. There are 108 genes with over expression and 327 genes in down-regulated both in PCA and LM group. Among them, 57 genes express higher in LM than PCA. HCS cell proliferation screening experiments prove that shRAB20, shAIM2, and shBCL2A1 inhibit cell proliferation with the ratio of 1.95,1.73 and 1.61 respectively,compared with shCtrl group.
Conclusions: RAB20, AIM2, and BCL2A1 genes are highly correlated with the proliferation of the mPSCC and its metastatic potential needs further confirmation.