ALDH1A1 Expression Has High Prognostic Value in Gastric Cancer

Gastric carcinoma; source: Wikimedia Commons

Expression of the protein aldehyde dehydrogenase 1 family member A1 (ALDH1A1) is associated with outcomes in gastric cancer, according to a new study. The results suggest that ALDH1A1 could be used as a prognostic tool.

ALDH proteins modulate cell proliferation, differentiation, and survival. “Recently, it has been reported that ALDH1A1 has been related to adverse prognosis in several human malignancies, including breast cancer, lung cancer, ovarian cancer, and esophageal cancer,” wrote researchers led by Wei-sheng Luo, MD, of the Affiliated Hospital of Guilin Medical University, in Guilin, China. The research group used immunohistochemistry to assess ALDH1A1 expression and correlated it with clinicopathological parameters and survival in 216 gastric carcinoma patients. Results were published online ahead of print in BMC Cancer.

Patients were followed for a median of 27 months. Half of the patients were positive for ALDH1A1 in gastric cancer samples. Levels of ALDH1A1 were significantly correlated with several parameters including depth of invasion (P < .001), lymph node metastasis (P < .001), and stage of disease (P < .001). Levels of the protein were not, however, associated with gender, age, tumor size or site, and grade of differentiation. “Notably, the correlation of ALDH1A1 with prominent serosal invasion and lymph node metastasis positivity suggested a potential role of ALDH1A1 in increased invasion and metastasis of gastric cancer,” the researchers wrote.

Expression levels of ALDH1A1 were among several factors significantly associated with overall survival in these patients; other significant factors included larger tumor size, prominent serosal invasion, and lymph node metastasis. ALDH1A1 expression and other factors were also significant negative predictors of recurrence-free survival.

On a multivariable analysis, ALDH1A1 expression yielded a hazard ratio (HR) for overall survival of 2.037 (95% CI, 1.407-2.950). Those who were positive for ALDH1A1 also had about a twofold risk of relapse than ALDH1A1-negative patients, with an HR of 1.945 (95% CI, 1.346-2.812). The postoperative median overall survival in ALDH1A1-positive patients was 12 months, compared to 42 months in ALDH1A1-negative patients. Median recurrence-free survival times for the two groups were 9 months and 39 months, respectively. At 5 years, 23.9% of ALDH1A1-positive patients were alive, compared with 57.1% of ALDH1A1-negative patients (P < .001).

The authors noted that the connection between ALDH1A1 status and tumor aggressiveness suggests the protein could eventually be a therapeutic target. For the moment, though, “determination of ALDH1A1 expression may help to identify high-risk gastric cancer patients and thus aid the selection of appropriate therapies.”