Abstract
More than 25% localized CRC patients died from post-operative metastasis, and risk of metastasis varies among individuals due to the high heterogeneity of CRC. Therefore, figuring out potential biomarkers for disease recurrence would be invaluable to improve the follow-up efficiency and clinical treatment. Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) is a core component of the nuclear receptor corepressor complex, which functions as a repressive coregulatory factor for multiple transcription factors. The clinical significance of TBL1XR1 in CRC hasn’t been fully elucidated. In this study, we investigated the expression of TBL1XR1 in primary CRC tissues and liver metastases from TNM stage IV CRC patients, and found that its expression in primary tumor tissues was an independent prognostic factor for tumor recurrence. Thus, we enrolled another cohort including TNM stage I-III patients to further evaluate the relationship between TBL1XR1 expression and disease recurrence. Accordingly, high TBL1XR1 expression indicates poor disease-free survival of stage I-III CRC patients. Furthermore, we confirmed the importance of β-catenin signaling pathways in TBL1XR1-mediated CRC cell oncogenicity by clinical and cellular results. Our results emphasize the necessity of individual therapy decisions based on clinical biomarkers, especially for localized CRC patients who are not routinely treated with adjunctive chemotherapy.
Highlights
We further enrolled another cohort which included stage I-III patients to evaluate whether TBL1XR1 can be helpful in predicting metastasis and recurrence
We performed cellular studies combined with gene overexpression and knock-down methods, and biofunctional studies revealed that β-catenin was the key molecular in regulating TBL1XR1-mediated cell proliferation and invasion
We selected 47 stage IV CRC patients with synchronous liver metastasis (CRCLM) as cohort I to investigate the possible relationship between TBL1XR1 and CRC metastasis
Summary
We further enrolled another cohort which included stage I-III patients to evaluate whether TBL1XR1 can be helpful in predicting metastasis and recurrence. Univariate and multivariate analyses showed that high expression of TBL1XR1 is an independent risk factor for post-operative recurrence of localized and regional CRC patients. We performed cellular studies combined with gene overexpression and knock-down methods, and biofunctional studies revealed that β-catenin was the key molecular in regulating TBL1XR1-mediated cell proliferation and invasion
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