title: TBL1XR1 predicts isolated tumor cells and micrometastasis in patients with TNM stage I/II colorectal cancer.
abstract: OBJECTIVE
  A considerable number of early-stage colorectal cancer (CRC) patients may develop cancer relapse or metastasis after curative surgery. Isolated tumor cells (ITC) and micrometastasis in lymph nodes (LNMM), which are undetectable by conventional pathological examination, may be one primary reason. Detection of ITC/LNMM is time-consuming and cost-ineffective; we aimed to find biomarkers in primary CRC tissues to help predicting ITC/LNMM status.
  
  
  METHODS
  We enrolled 137 node-negative patients with early-stage CRC in this study. Existence of ITC/LNMM was identified by immunohistological staining with cytokeratin 20 in resected lymph nodes. Expression of transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) in primary CRC tissues was also investigated. Chi-squared test was performed to reveal the correlations between ITC/LNMM and clinicopathological characteristics. Univariate and multivariate analyses were used to determine independent prognostic factors. Knockdown experiment together with proliferation and invasion assays were carried out to explore molecular mechanisms between TBL1XR1 and ITC/LNMM.
  
  
  RESULTS
  About 29.2% (40/137) patients were identified as ITC/LNMM positive, and most of them (32/40 cases, 80%) showed high TBL1XR1 expression in primary CRC tissues. Both ITC/LNMM and TBL1XR1 expression were independent prognostic factors for disease relapse or metastasis. In vitro experiments demonstrated that TBL1XR1 can regulate the expression of vascular endothelial growth factor C and epithelial-mesenchymal transition proteins, thus mediate the process of lymph node metastasis.
  
  
  CONCLUSIONS
  Identification of ITC/LNMM is significant in evaluating clinical outcome and guiding adjuvant chemotherapy for early-stage CRC patients. TBL1XR1 overexpression in CRC tissues can serve as an efficient biomarker to predict the status of ITC/LNMM.
authors.affiliation: Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Hongda
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Zhaochen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Kangshuai
authors.initials: K
authors.lastname: Li
authors.affiliation: 302 Military Hospital of China, Beijing, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Urological Organ Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Breast Surgery, Qianfoshan Hospital, Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Weichen
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Gastrointestinal Surgery, Qianfoshan Hospital, Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Shanglei
authors.initials: S
authors.lastname: Ning
authors.affiliation: Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Sayed
authors.initials: S
authors.lastname: Ismail
authors.affiliation: Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D061206:Neoplasm Micrometastasis / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011237:Predictive Value of Tests; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C473691:TBL1XR1 protein, human
keywords: TBL1XR1; colorectal cancer; isolated tumor cells; lymph node micrometastasis