HOXC9 overexpression is associated with gastric cancer progression and a prognostic marker for poor survival in gastric cancer patients

Int J Clin Oncol. 2020 Dec;25(12):2044-2054. doi: 10.1007/s10147-020-01772-0. Epub 2020 Aug 20.

Abstract

Background: As a member of the homeobox family, HOXC9 is overexpressed in several malignant tumors and may be regarded as a biomarker for prognostic evaluation. However, the expression pattern and prognostic significance of HOXC9 in gastric cancer have not been detailedly studied.

Methods: HOXC9 mRNA expression difference in normal tissues and gastric cancer tissues were investigated using RT-PCR, and immunohistochemistry was used to analyze HOXC9 protein expression in precancerous lesions and gastric cancer at different stages, and its clinicopathological characteristics and survival were statistically tested.

Results: Compared to the normal gastric mucosa tissues, the expression levels of HOXC9 mRNA in the human gastric cancer tissues were significantly higher. HOXC9 protein levels of gastric cancer were obviously higher than that in other noncancerous tissues (P < 0.001). Positive expression of HOXC9 was associated with tumor size (P = 0.036), lymphatic invasion (P = 0.001), depth of invasion (P < 0.001), lymph-node metastasis (P < 0.001), and higher stage disease (P < 0.001). Furthermore, Kaplan-Meier survival curves showed that HOXC9 expression is inversely correlated with both disease-specific and disease-free 5 year survival of patients with gastric cancer (P < 0.001 for both). Strikingly, our multivariate Cox regression analysis revealed that HOXC9 expression was an independent poor prognostic factor in gastric cancer (P < 0.05).

Conclusions: HOXC9 expression was observed in a subset of patients with gastric cancer and was associated with an unfavorable prognosis. As well as being a new prognostic indicator, HOXC9 protein could be a useful marker for early diagnosis.

Keywords: Early diagnosis; Gastric cancer; HOXC9; Prognosis.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Homeodomain Proteins
  • Hoxc9 protein, human