Expression of HAX-1 in human colorectal cancer and its clinical significance

Abstract

Colorectal cancer (CRC) remains one of the most common cancers worldwide. HS1-associated protein X-1 (HAX-1) has been highlighted as an important marker in many types of cancers. However, little is known about the role of HAX-1 in CRC. The aim of this study was to analyze the correlation of HAX-1 expression with the clinicopathological features of CRC. The protein and mRNA levels of HAX-1 were examined by immunohistochemistry (IHC) and real-time quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) in CRC tissues and adjacent noncancerous tissues. Survival curves were made with follow-up data. The relations of the prognosis with clinical and pathological characteristics were analyzed. Using IHC and RT-qPCR, we showed that HAX-1 expression was significantly higher in CRC tissues than in adjacent noncancerous tissues (P < 0.05). High HAX-1 expression was significantly associated with lymph node metastasis (P = 0.034) and tumor (T) node (N) metastasis (M) stage (P = 0.028) of patients with CRC. The Kaplan-Meier survival curves indicated that overall survival was significantly worse in CRC patients with HAX-1 overexpression. Multivariate analysis showed that high HAX-1 expression was an independent predictor of overall survival. In conclusion, our data for the first time provide a basis for the concept that overexpression of HAX-1 may contribute to the malignant progression of CRC and predict poor prognosis for patients with this disease. HAX-1 might be an important marker for tumor progression and prognosis, as well as a potential therapeutic target of CRC.

Clinical significance of HAX-1 expression in laryngeal carcinoma

“…This finding was consistent with previous reports from other tumors [12][13][14][15]. We found that compared with adjacent non-tumor tissues the strong positive rate of HAX-1 were significantly higher in laryngeal carcinoma samples.…”

“…A final immunoreactivity score (IRS) was obtained for each case by multiplying the percentage and the intensity score. Protein expression levels were further analyzed by classifying IRS values as low (based on an IRS value lower than 4.5 which was the median of IRS values) and as high (based on an IRS value greater than 4.5 which was the median of IRS values) [13]. Ethics approval to perform this study was obtained from the Human Research Ethics Committee of the Affiliated Hospital of Nantong University, Jiangsu Province, China.…”

“…HAX-1 was implicated in a perplexing range of important biological functions including the regulation of apoptosis or programmed cell death, cell motility, endocytosis and calcium homeostasis, and involvement in multiple signaling pathways and cellular processes through interacting with a number of cellular and viral proteins such as polycystin-2, cortactin and Epstein-Barr virus nuclear antigen leader protein (EBNA-LP) [4][5][6][7][8][9][10][11]. Analysis of gene expression profiles revealed that the amounts of the HAX-1 gene were significantly elevated in a broad variety of cancers, including esophageal squamous cell carcinoma (ESCC), colorectal cancer (CRC), oral squamous cell carcinoma, lung cancer, lymphoma, melanoma, breast cancer and hepatoma [6,[12][13][14][15][16][17][18][19]. More recently, it was determined that the level of increase in HAX-1 gene expression correlated with the size and grade of the tumor, with higher amounts of HAX-1 detected as the disease progressed, at least for breast cancer [16].…”

Hax-1 is required for Rac1-Cortactin interaction and ovarian carcinoma cell migration

“…Recently, it has also been observed that the homozygous mutations in Hax-1 gene or loss of Hax-1 are associated with severe congenital neutropenia and neurodevelopmental disorders. In addition, overexpression of Hax-1 has been observed in tissues from esophageal, lung and colon cancers [13, 14, 17, 20]. More significantly, in colorectal cancer the increased expression of Hax-1 correlates with the lymph node metastasis and poor prognosis of the patients[13].…”

“…Subsequent studies from several laboratories including ours have clearly established a crucial role for Hax-1 in cancer cell migration [5, 10-12]. More recently it has been shown that Hax-1 is overexpressed in many cancers and the increased expression of Hax-1 can be correlated with aggressive cancer metastasis[13-20]. Collectively these studies point to a novel, but yet to be resolved role for Hax-1 in tumor cell migration and metastasis.…”