Abstract 2556: Enhanced expression of human cyclin G1 (CCNG1) gene in metastatic cancer, a novel biomarker in development for CCNG1 inhibitor therapy

Abstract

Abstract Background: Metastatic cancer is associated with, hitherto, an invariably fatal outcome. DeltaRex-G, a CCNG1 inhibitor, has induced long term (9-12 year-) survivorship in patients with metastatic melanoma, sarcoma, lymphoma and cancer of pancreas and breast. Purpose: To evaluate CCNG1 expression in tumors as a novel biomarker for identification of patients who are likely to benefit from CCNG1 inhibitor therapy. Methods: RNA sequence analysis was used to compare CCNG1 expression in tumor (TCGA, N=9161) versus normal tissues (TGCA, N=678 and GTEx, N=7187) from 20 organ sites, and in primary vs metastatic melanoma (N=106 & 367 respectively). Using IHC staining, the significance of differences between the number of CCNG1+ and Ki-67+ cells in normal tissues vs tumors were evaluated using paired Student’s t test. Pearson’s coefficient of correlation was used to evaluate the relationship between the number of Ki-67+ vs CCNG1+ cells. Results: CCNG1 gene expression, by RNA sequence analysis, was significantly enhanced in melanoma, sarcoma, leukemia, and cancers of the lung, thyroid, brain, liver, prostate, testicle, head and neck, bladder, kidney, adrenal, cervix, and pancreas, compared to normal tissues (p = 0.006- 1.8E-58), and even greater, in metastatic vs primary melanoma. In a subset of melanoma tumors, there was overall positive correlation with progression/metastasis in both Ki67 and CCNG1 expression levels. Consistent with these findings, IHC showed significant differences when comparing CCNG1 nuclear staining percentages between analogous healthy and cancerous tissues (p = 0.002, df = 11). The nuclear staining percentages of CCNG1 and Ki-67 share a statistically significant, positive correlation (r = .936977, p < 0.00001). Further, in some patients, the level of CCNG1 expression by IHC fluctuated over time. Conclusion: Taken together, these data indicate that (1) CCNG1 expression, is frequently enhanced in cancerous tumors compared to their normal analogous counterparts, and (2) the level of CCNG1 expression may change over time, necessitating real time analysis in order to determine the optimal timing for CCNG1 inhibitor therapy. A Phase 2 basket study of DeltaRex-G cell cycle checkpoint inhibitor therapy is planned to correlate treatment outcome parameters with CCNG1 expression in patients’ tumors and circulating tumor cells. Citation Format: Erlinda M. Gordon, Christopher Szeto, Joshua R. Ravicz, Sandeep Reddy, Michael Morse, Sant Chawla, Frederick Hall. Enhanced expression of human cyclin G1 (CCNG1) gene in metastatic cancer, a novel biomarker in development for CCNG1 inhibitor therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2556.