Abstract
The majority of occult liver metastases cannot be detected by computed tomography (CT), magnetic resonance imaging (MRI) or other traditionally morphological imaging approaches since the lesions are too small or they have not yet formed cancer nodules. Gankyrin is a small molecular protein composed of seven ankyrin domains. In this study, the expression of Gankyrin in colorectal cancer (CRC) patients with liver metastases was investigated to determine its prognosis value. Gankyrin expression in CRC patients was initially analyzed using data from The Cancer Genome Atlas (TCGA) database and bioinformatics tools. RT-qPCR, western blotting, immunohistochemistry (IHC) and transwell migration and invasion assays were then performed to verify the expression and function of Gankyrin in CRC cell line, CRC tissues and matched non-tumor tissues of clinical patients. General clinicopathological information including TNM stage as well as preoperative and postoperative imaging results were collected. The main outcome indicator was overall survival (OS), referring to the length of time from surgery to either death or the last visit. Statistical analyses included chi-squared tests, Cox analyses, progression free survival (PFS) rates and OS rates. Elevated Gankyrin expression was confirmed in CRC patients. The upregulated Gankyrin expression was positively correlated with the progression of disease and liver metastasis in CRC patients. OS analysis revealed that prognosis was worse in CRC patients with high Gankyrin expression compared to those with low expression. CRC patients with higher Gankyrin expression also had a higher risk of occult liver metastases and a lower PFS rate. Therefore, Gankyrin can be used as a potential biomarker for early diagnosis of CRC with occult liver metastasis.
Highlights
Metastasis is a biological characteristics of malignant tumors, and poses a challenge in clinical practice [1]
The Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) results revealed that the expression of Gankyrin mRNA in most colorectal cancer (CRC) tissues was higher compared to nontumor tissues (36/40; Figure 2A)
In most cases (146/150), the H-score of Gankyrin was higher in CRC tissues compared to matched non-tumor colorectal tissues (Figure 2C), which was in line with both the RT-qPCR and western blot data
Summary
Metastasis is a biological characteristics of malignant tumors, and poses a challenge in clinical practice [1]. Considerable progress has been made regarding the diagnosis and treatment of tumors, but tumor metastases are still responsible for 90% of cancer-related deaths. For colorectal cancer (CRC) patients, liver metastasis is the leading cause of mortality. It has been reported that 70% of patients who died of CRC had metastatic liver disease [2]. The early diagnosis of liver metastasis in CRC strongly influences the choice of treatment and prognosis. Most occult liver metastases cannot be detected by computed tomography (CT), magnetic resonance imaging (MRI) or other traditional morphological imaging techniques since the lesions can be very small or may not have yet formed cancer nodules [3]. A simple technique for early detection of occult liver metastases in CRC patients is an important measure to investigate to improve overall survival (OS) rates and quality of life
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