Significance and prognostic role of human epidermal growth factor receptor 2 and RAB1A expression in gastric cancer

Abstract

Abstract. Human epidermal growth factor receptor 2 (HER-2) has an important clinical role in various cancers. However, the prognostic impact of HER-2 in gastric cancer (GC) is controversial. RAB1A is an important small molecule in the mechanistic target of rapamycin signalling pathway, which is one of the downstream signalling pathways of the epidermal growth factor receptor family. In recent years, the aberrant expression of RAB1A has been reported in a number of tumours, but its regulation in GC has not been extensively examined. Therefore, the present study investigated the expression pattern and prognostic significance of HER-2 and RAB1A in gastric adenocarcinoma (CAG). A comprehensive analysis was performed to examine the expression level of HER-2 and RAB1A in 280 cases of paired paraffin-embedded GAC tissues and an additional 120 archived GAC tissue samples. HER-2 and RAB1A protein expression was assessed by immunohistochemistry and cases with a 2+ score for HER-2 expression levels were subjected to fluorescence in situ hybridization to determine the HER-2 amplification status. Furthermore, HER-2 and RAB1A mRNA expression was quantified by reverse transcription-quantitative polymerase chain reaction. The comparison of continuous data between two groups was performed using a paired-samples t-test. Clinical correlations were determined using Pearson's Chi-square and Fisher's exact tests. Kaplan-Meier survival curves were used to estimate overall survival (OS). Cox proportional hazards models were used to determine associations between HER-2 and RAB1A expression and outcomes. Regression analyses were performed to detect the correlation between the mRNA levels of HER-2 and RAB1A in GAC tissues. It was observed that RAB1A was significantly overexpressed in GAC tissues compared with normal tissues (P<0.001). Approximately 12.86% of the 280 GAC patients had HER-2 amplification. Additionally, RAB1A expression was significantly associated with a short OS (P<0.001) but there were no significant differences in survival between the HER-2 high-expression group and the HER-2 low-expression group. Additionally, the co-expression of HER-2 and RAB1A indicated poorer OS than the overexpression of each protein (P=0.001), and the two factors were significantly positively correlated in GAC (P= 0.012). These findings may be used to further explore the molecular mechanisms and regulatory associations among signalling pathways in GC.

Rab1A promotes proliferation and migration abilities via regulation of the HER2/AKT-independent mTOR/S6K1 pathway in colorectal cancer

“…Previous studies have demonstrated that Rab1A overexpression leads to poor survival in HCC (11) and gastric cancer (32). In accordance with a previous study in HCC (11), we found that the survival of Rab1A-positive patients was significantly worse than that of Rab1A-negative patients and higher Rab1A expression was associated with a worse 5-year survival rate in patients with I–II and III–IV disease staging.…”

Expression analysis and implication of Rab1A in gastrointestinal relevant tumor

“…However, we did not observe any obvious changes in Rab1A expression between the early and advanced TNM stages in the above cancers. Recent studies have also correlated Rab1A overexpression with poor prognosis in several gastrointestinal cancers, such as CRC and GC 5,22 . Consistent with these reports, we observed that lower Rab1A expression indicated better prognosis in liver hepatocellular carcinoma and pancreatic adenocarcinoma.…”

“…Rab1A is a small GTPase that regulates ER-to-Golgi vesicular transport 17,18 . Recent studies show that Rab1A acts as an oncogene and is overexpressed in various cancers 19–21 , especially those affecting the gastrointestinal system, such as colorectal cancer 5 , gastric cancer 22 , hepatocellular carcinomas etc. 23,24 .…”

<p>Trastuzumab with FLOT Regimen for the Perioperative Treatment of Resectable HER2 + Advanced Gastric Cancer: A Retrospective Study</p>

“…4 HER-2 expression in gastric cancer was more invasive and the prognosis of patients was worse, but HER-2 was also an effective predictor of trastuzumab treatment. 5 A stage III ToGA clinical study showed that the efficacy of trastuzumab combined with an XP/FP regimen in patients with HER-2-positive advanced esophagogastric junction or gastric cancer was significantly better than that of patients receiving only chemotherapy. Median OS was 13.8 months (95% confidence interval [CI] [12][13][14][15][16] for patients assigned to the trastuzumab plus chemotherapy arm compared with 11.1 months (95% CI [10][11][12][13] in the chemotherapy group (hazard ratio [HR] 0.74; 95% CI 0.60--0.91; p = 0.0046).…”