title: Increased expression of DLX2 correlates with advanced stage of gastric adenocarcinoma.
abstract: OBJECTIVE
  To investigate the expression of distal-less homeobox 2 (DLX2) in gastric adenocarcinoma and its clinicopathological significance.
  
  
  METHODS
  Gastric adenocarcinoma tissues were obtained from gastrectomy specimens of 129 patients from the Department of Surgery and Pathology, the Second Affiliated Hospital of Kunming Medical University. Sixty cases of normal gastric tissues were collected from gastrectomy specimens of adjacent gastric cancer margins greater than 5 cm. Patient diagnosis was established pathologically, and no patient had received chemotherapy or radiotherapy before surgery. All tissue specimens were formalin-fixed and paraffin-embedded. Immunohistochemistry was carried out to investigate the expression of DLX2 in 129 gastric adenocarcinoma tissues and 60 adjacent normal tissues. The immunostaining reaction was semiquantitatively evaluated based on the proportion of positive cells and the median staining intensity in normal gastric epithelial cells or tumor cells. All patients had follow-up records for more than 5 years. Correlations of DLX2 expression with clinicopathological features and prognosis of patients with gastric adenocarcinoma were analyzed. All statistical analyses were performed using the SPSS 17.0 software.
  
  
  RESULTS
  The positive expression of DLX2 was detected in 68 (52.7%) cases of 129 gastric adenocarcinoma tissues and 14 (23.3%) cases of 60 adjacent normal tissues. The difference in DLX2 expression between gastric adenocarcinoma tissues and adjacent normal tissues was statistically significant (χ² = 14.391, P < 0.001). Moreover, high expression of DLX2 was detected in 48 (37.2%) cases of 129 human gastric cancer tissues, but not in adjacent normal tissues. The expression of DLX2 correlated with the size of tumor (P = 0.001), depth of invasion (P = 0.008), lymph node metastasis (P = 0.023) and tumor-node-metastasis stages (P = 0.020), but was not correlated with age, gender, histological differentiation and distant metastasis. The Kaplan-Meier survival analysis revealed that survival time of patients with high DLX2 expression was significantly shorter than that with low DLX2 expression. However, the multivariate analysis showed that invasion depth (P < 0.001), lymph nodes metastasis (P = 0.001) and distant metastasis (P < 0.001) were independent prognostic factors for patients with gastric adenocarcinoma, but DLX2 expression, tumor location and tumor size were not.
  
  
  CONCLUSIONS
  These results suggest that increased expression of DLX2 may correlate with the advanced stage of gastric adenocarcinoma, and it may contribute to tumor development.
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Tang
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.forename: Gong-Fang
authors.initials: GF
authors.lastname: Zhao
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: Lu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D016009:Chi-Square Distribution; D005260:Female; D005743:Gastrectomy; D018398:Homeodomain Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D014157:Transcription Factors / Q000032:analysis*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors
keywords: Distal-less homeobox 2; Gastric adenocarcinoma; Immunohistochemistry; Invasion; Metastasis; Prognosis