RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases

Abstract

Introduction: Regulator of chromatin condensation 1 (RCC1) is a major guanine-nucleotide exchange factor for Ran GTPase, and it plays key roles in various biological processes. Previous studies have found that RCC1 may play a role in the development of tumors, but little is known about the relationship between RCC1 and colorectal liver oligometastases (CLOs).Methods: One hundred and twenty-nine pairs of matched human CLO samples, including both primary tumor and its liver metastasis specimens, were subjected to immunohistochemistry to determine the location and expression levels of RCC1. Associations between RCC1 and survival as well as gene expression profiling were explored.Results: In this study, we first observed that RCC1 was mildly increased in CLO tumor tissues compared with normal tissues, and the localization was primarily nuclear. In addition, our study found that high RCC1 expression in liver oligometastases was an independent prognostic marker for unfavorable recurrence-free survival and overall survival (p = 0.036 and p = 0.016). Gene expression profiles generated from microarray analysis showed that RCC1 was involved in pathways including “Myc targets,” “E2F targets” and “DNA repair” pathways.Conclusion: Our data indicated that RCC1 was expressed mainly in the nucleus, and strong and significant associations were found between RCC1 expression levels and the survival of CLO patients. These findings indicated that RCC1 may play a role in CLO development.

RCC1 functions as a tumor facilitator in clear cell renal cell carcinoma by dysregulating cell cycle, apoptosis, and EZH2 stability

“…[14][15][16] Recent studies reported that RCC1 regulates immunological pathways and promotes the growth of some malignant solid tumors. [17][18][19][20][21] For example, in lung cancer, RCC1 was shown to regulate the tumor sensitivity to immunotherapy by controlling PD-L1 expression. 17 In glioblastoma, RCC1 knockdown promoted the effect of radiation on tumor stem cells.…”

Systematic pan-cancer analysis on the expression and role of regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene 12

“…It has been shown that RCC1 was identified as a candidate breast cancer susceptibility gene in the Tunisian population by exome sequencing and case-control analysis (Riahi et al, 2018). Other trials have found a strong and significant association between RCC1 expression levels and survival in patients with Colorectal Liver Oligometastases (Deng et al, 2021). In a study of non-small cell lung cancer, knockdown of RCC1 not only significantly inhibited the proliferation of cancer cells but also reduced the volume and weight of tumor models after PD-L1 monoclonal antibody treatment (Zeng et al, 2021).…”

Antinuclear antibodies in individuals with COVID-19 reflect underlying disease: Identification of new autoantibodies in systemic sclerosis (CDK9) and malignancy (RNF20, RCC1, TRIP13)

“…1 A, #3). RCC1 has a nuclear localization [ 20 ]. UTP4 [ 21 ], NLE1 [ 22 ], NOC2L [ 23 ], TOP2B [ 24 ] are located in the nucleolar area, and TOP2A is located in the nucleolar area and the nucleoplasm [ 24 ].…”

“…RCC1 is a chromatin-bound guanine nucleotide exchange factor for the Ras-related nuclear protein [ 25 ]. RCC1 levels have been reported to be significantly higher in primary colorectal tumors and liver metastases than in normal tissues [ 20 ]. High RCC1 expression in liver oligometastases was an independent prognostic marker for unfavorable recurrence-free survival and overall survival [ 20 ].…”

“…RCC1 levels have been reported to be significantly higher in primary colorectal tumors and liver metastases than in normal tissues [ 20 ]. High RCC1 expression in liver oligometastases was an independent prognostic marker for unfavorable recurrence-free survival and overall survival [ 20 ]. An increased expression of TOP2A in rectal tumors has been described [ 26 ].…”