Identification and validation that up-expression of HOXA13 is a novel independent prognostic marker of a worse outcome in gastric cancer based on immunohistochemistry

Abstract

Homeobox (HOX) gene family is known to be classic examples of the intimate relationship between embryogenesis and tumorigenesis. However, less is known about the involvement of HOX gene family with gastric cancerogenesis. Here, we screened the expression of HOX gene family in gastric cancers and explored the relationships between them by cDNA microarray. We found several differentially expressed HOX genes in gastric cancers, especially HOXA10 (11/12) and HOXA13 (11/12) with significantly higher expression in the cancerous tissues. Furthermore, we validated HOXA13 as a novel prognostic marker in gastric cancer based on immunohistochemistry and statistical analysis. HOXA13 expression was significantly up-regulated in cancerous tissues compared with the corresponding non-cancerous mucosa (P < 0.001). Up-expression of HOXA13 was significantly correlated with T stage (P = 0.002), M stage (P = 0.024), advanced UICC stage (P < 0.001), histological differentiation (P = 0.005), and relapse (P = 0.001). Patients with positive HOXA13 expression had a obviously lower overall survival (OS) and disease-free survival (DFS) rate than patients with negative HOXA13 expression (HR 3.331, 95 % CI 1.722-6.442, P < 0.001; HR 3.289, 95 % CI 1.703-6.351, P < 0.001, respectively). Univariate and multivariate Cox analysis confirmed that HOXA13 could serve as a significant independent prognostic factor for DFS and OS. Therefore, our results indicated that several HOX genes might be closely involved in the process of the gastric tumorigenesis. Furthermore, up-expression of HOXA13 might be associated with highly aggressive phenotype of gastric cancer. HOXA13 was a significant independent prognostic factor and could serve as a putative biomarker for diagnosis and prognosis of gastric cancer.

Overexpression of HOXB7 is associated with a poor prognosis in patients with gastric cancer

“…It has previously been found that HOXB7 is upregulated in gastric cancers, which was determined using a cDNA microarray (15). The present study identified that HOXB7 was upregulated in gastric cancer at the mRNA and protein levels by RT-qPCR and western blot analysis.…”

“…The results revealed that several HOX genes were differentially expressed in gastric cancers, including the high-expression genes HOXA1, HOXA4, HOXA10, HOXA13, HOXB7 and HOXC10, and the low-expression genes HOXC5 and HOXC8 (15). Among these genes, HOXB7 was highly expressed more frequently in gastric cancer tissues (9/12 tissues) compared with the corresponding normal tissues.…”

HOTAIR: a cancer-related long non-coding RNA

“…By the way of above, HOX genes can affect genes transcription by specifying the positional identities of chromosomes [43]. Aberrant expressions of HOX genes may affect cells differentiation and ontogeny, causing abnormal tissues and organs, and even contribute to a variety of tumors, such as ovarian cancer [44], gastric cancer [45], colorectal cancer [46,47], neuroblastoma [48], kidney cancer [49], prostate cancers [50] and hematological malignancies [51,52,53].…”

Long non-coding RNA HOXA transcript at the distal tip as a biomarker for gastric cancer

“…It was reported that HOTTIP may regulate the expression of HOX genes, including HOXA1, HOXA9, HOXA10, HOXA11 and HOXA13, in liver cancer and pancreatic cancer (15)(16)(17). In addition, numerous studies have reported that aberrant expression of HOXA genes was associated with a number of biological characteristics of gastric cancer (34)(35)(36)(37). HOTTIP may be critical in regulating HOXA genes in gastric cancer, but the underlying mechanism remains unknown and requires additional study.…”