Discovery of Cancer Prognostic Factors

My group has been working on cancer marker through genomics and proteomics for 18 years. We discovered IGFBP2 as a marker for high-grade glioma as well as some other cancer types. We also discovered miR-141 as a plasma marker for colorectal cancer.

As one of the seven Genome Data Analysis Centers of TCGA, we have been working on several cancer types. Focusing on the serous ovarian cancer dataset, we investigated the role of BRCA1 and BRCA2 mutations in the prognosis of this cancer and discovered that BRCA2 mutations confer the most robust effects clinically. BRCA2-mutated ovarian cancers are more responsive to front-line chemotherapy and have longer overall and progression-free survival. This clinically significant finding was published in JAMA (306:1557-65, 2011).

This study has been highlighted at the TCGA website. Our recent identification of the core miRNA regulatory network for mesenchymal ovarian cancer was published in Cancer Cell (23:186–199, 2013). In this paper, we identified a novel EMT-inhibitory miRNA, miR-506.

We showed, in multiple datasets covering more than 1000 patients, that miR-506 is associated with better prognosis and response to cisplatin. This study was highlighted on the cover of Cancer Cell and at the TCGA website. MiR-506 has been shown to serve as an important tool in the management of ovarian cancer, and this result has been validated by a number of recent publications.

Our continued characterization of miR-506 in EMT and cellular senescence has led to two recent publications in the Journal of Pathology (one highlighted on the cover). Our most recent investigation has shown that miR-506 targets Rad51 and sensitizes cancer cells to chemotherapy. This paper was recently published in JNCI (2015 May 20;107(7).). This is one of the major research focus in my group – linking genetic markers to therapy and therapeutic responses.

Selected Research

Yang D, Khan S, Sun Y, Hess K, Shmulevich I, Sood AK, Zhang W. Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA 306(14):1557-65, 2011.

Yang D, Sun Y, Hu L, Zheng H, Ji P, Pecot CV, Zhao Y, Reynolds S, Cheng H, Rupaimoole R, Cogdell D,Nykter M, Broaddus R, Rodriguez-Aguayo C; Lopez-Berestein G, Liu J, Shmulevich I, Sood A*, Chen K, and Zhang W. A Core microRNA Network Defines a Mesenchymal Subtype of Ovarian Cancer with Poor Survival. Cancer Cell 23, 186–199, 2013.

Liu G, Yang D, Rupaimoole R, Pecot CV, Sun Y, Mangala LS, Li X, Ji P, Cogdell D, Hu L, Wang Y, Rodriguez-Aguayo C, Lopez-Berestein G, Shmulevich I, De Cecco L, Chen K, Mezzanzanica D, Xue F, Sood AK, Zhang W. Augmentation of Response to Chemotherapy by microRNA-506 Through Regulation of RAD51 in Serous Ovarian Cancers. J Natl Cancer Inst. 2015 May 20;107(7).