Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Enhanced Expression of Human Cyclin G1 (CCNG1) in Tumors, a Novel Biomarker in Development for Cancer Therapy/Gene Therapy

Version 1 : Received: 7 March 2021 / Approved: 8 March 2021 / Online: 8 March 2021 (11:55:01 CET)

How to cite: Ravicz, J.; Szeto, C.; Reddy, S.; Chawla, S.; Morse, M.; Gordon, E. Enhanced Expression of Human Cyclin G1 (CCNG1) in Tumors, a Novel Biomarker in Development for Cancer Therapy/Gene Therapy. Preprints 2021, 2021030213 (doi: 10.20944/preprints202103.0213.v1). Ravicz, J.; Szeto, C.; Reddy, S.; Chawla, S.; Morse, M.; Gordon, E. Enhanced Expression of Human Cyclin G1 (CCNG1) in Tumors, a Novel Biomarker in Development for Cancer Therapy/Gene Therapy. Preprints 2021, 2021030213 (doi: 10.20944/preprints202103.0213.v1).

Abstract

Background: Metastatic cancer is associated with an invariably fatal outcome. However, DeltaRex-G, a tumor- targeted retrovector encoding a CCNG1 inhibitor gene, has induced long term (>10 years) survival of patients with chemo-resistant metastatic pancreatic adenocarcinoma, MPNST, osteosarcoma, B-cell lymphoma, and breast carcinoma. Objective: To evaluate the level of CCNG1 expression in tumors as a potential biomarker for CCNG1 inhibitor therapy. Methods: CCNG1 RNA expression levels were measured in tumors (TCGA, N=9161), adjacent “tissues” (TCGA, N=678) and GTEx normal tissues (N=7187) across 22 organ sites. Differential expression of CCNG1 and Ki-67 in primary (N= 9161) vs metastatic (N= 393) tumors were also compared and particularly in primary (N=103) vs. metastatic (N=367) skin cancer (i.e., melanoma). Results: Enhanced CCNG1 RNA and protein expression were noted in tumors compared to normal analogous counterparts, and CCNG1 expression correlated significantly with that of Ki-67. Further, CCNG1 expression tended to be higher than that of Ki-67 in metastatic vs primary tumors, particularly in skin cancer (melanoma). Conclusions: Taken together, these data indicate that (1) CCNG1 expression is frequently enhanced in tumors when compared to their normal analogous counterparts, (2) CCNG1 and Ki-67 expressions are higher in metastatic vs primary tumors, (3) CCNG1 expression is significantly correlated with that of Ki-67, and (4) CCNG1 may be a stronger marker of metastasis than Ki-67. Phase 2 studies are planned to identify patients who are likely to respond favorably to CCNG1 inhibitor therapy by correlating treatment outcome parameters with CCNG1 expression levels in various cancer types.

Keywords

DeltaRex-G; human cyclin G1; cell cycle control; cancer gene therapy; oncogenic drivers

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