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.
Highlights
Regulator of chromatin condensation 1 (RCC1) is a major guaninenucleotide exchange factor for Ran GTPase, and it plays key roles in various biological processes
The right-sided Colorectal cancer (CRC) tumors arise from cecum, ascending colon, and proximal two thirds of the transverse colon and the left-sided CRC tumors arise from the descending, sigmoid colon, rectum, and distal one third of the transverse colon
In 129 patients, RCC1 expression was detected in 70 primary tumors and matched normal tissues as well as in 129 liver metastases
Summary
Regulator of chromatin condensation 1 (RCC1) is a major guaninenucleotide 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). The 5-years overall survival rate for CRC patients with early-stage disease is 90%, but it significantly drops to 10% for advanced-stage CRC [3, 4]. Effective control of tumor progression, such as liver resection, can significantly prolong the survival of patients with colorectal liver oligometastases (CLOs), leading to a 5-years overall survival (OS) rate of 45.9% [7]. For those patients, the biological process of tumor development may be different. Exploring new biomarkers to identify highrisk patients and clarifying the underlying mechanisms are highly warranted
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