Expression Of ALDH1A1 And CD133 In Stage Ⅲ Gastric Cancer And Their Application In The Selection Of Adjuvant Chemotherapy

Objective: Gastric cancer is one of the most common malignancies in the world.Gastrectomy combined with postoperative adjuvant chemotherapy has become a recognized treatment for resectable gastric cancer.Even if the prime tumor is completely removed,it may recur.In recent years,cancer stem cells(CSCs)are considered to make an important role of tumor development,drug resistance,tumor invasion,metastasis and tumor recurrence.And CSCs are also correlated with cancer-related death.At present,it has been reported that acetaldehyde dehydrogenase-1A1(ALDH1A1)and CD133 may become cancer stem cell markers to predict tumorigenesis and prognosis.In this article,we used immunohistochemical staining to detect the distribution and expression of ALDH1A1 and CD133 in tissues of gastric cancer.Methods: The expressions of ALDH1A1 and CD133 in 91 cases of gastric cancer and 70 cases of para-tumor gastric tissues were detected by immunohistochemistry.SPSS 25.0 was used to analyze the relationship between clinicopathological features and prognosis of gastric cancer,as well as the effects on different treatment regiments.Results: In 91 patients with stage III disease,57(62%)patients were positive for ALDH1A1 and 60(66%)patients were positive for CD133.The expression of ALDH1A1 was detected in both gastric cancer tissues and para-tumor tissues,and the expression of ALDH1A1 in gastric cancer tissues was stronger than that in para-tumor tissues.Expression of CD133 was only detected in gastric cancer tissues.The positive expression of ALDH1A1 was significantly correlated with later T/N stage(T stage:P=0.012,N stage: P=0.023)and the degree of differentiation(P=0.020).The positive expression of CD133 was significantly related with later T stage related(P=0.007).Spearman rank correlation test showed a weak positive correlation between ALDH1A1 and CD133 expression levels(rs=0.240,P=0.022).Univariate analysis showed that CD133-positive was relevant with poor DFS(P=0.042),whereas ALDH1A1-positive gastric cancer was not relevant with poor DFS.Cox analysis showed that tumor stage,CD133 expression,vascular invasion and gender were independent prognostic factors for DFS.Tumor size,vascular invasion and gender were independent prognostic factors for OS.As for adjuvant chemotherapies,compared with two-drug group(platinum plus fluorouracil),the taxane-based three-drug group(taxane,platinum and fluorouracil)did not show a significant improvement in survival.Subgroup analysis showed that in the ALDH1A1 negative,as well as CD133-positive and ALDH1A1-negative subgroups,the OS rates in the two-drug group was significantly different from the three-drug group(P=0.043).Conclusion: ALDH1A1 and CD133 may play an important role in tumor invasion,metastasis and prognosis.It would be used as a target for predicting tumor prognosis and guiding treatment as a tumor stem cell marker.As for treatment,negative expression of ALDH1A1 is not beneficial from taxane-based three-drug chemotherapy regimen for patients with gastric cancer.