GC is the fifth most common cancer in the world and the fourth leading cause of cancer mortality26,27. Although the development of various diagnostic and treatment strategies for gastric cancer, but the five-year survival rate is still less than 30%, mainly because most patients with gastric cancer are diagnosed as advanced stage or even have distant organ metastasis. Secondly, the resistance of chemotherapy drugs is also an important reason for poor prognosis of patients with advanced gastric cancer28. Therefore, early diagnosis and finding new therapeutic targets have become urgent needs.
Rab1A is a member of the RAB family and a small GTPase that has been studied frequently7. Rab1A is anchored to the endoplasmic reticulum and Golgi membrane and is mainly expressed in the endoplasmic system8,9. With the deep exploration of Rab1A, previous studies proved that Rab1A was widely expressed in the ER, which would increase the pressure of the ER and promote cell apoptosis29. Rab1A not only participates in the transport of substances between membrane systems, but also plays an important role in the transmembrane signal transmission between cells10.
Recent studies have reported that Rab1A, as an oncogene, is aberrantly elevated in various of cancer. Furthermore, Rab1A overexpression led to poor prognosis, such as lung cancer16, liver cancer 17, colorectal cancer30. Previous study reported that the expression of Rab1A and IL4Ra is highly correlated in lung cancer tissues25. However, the potential correlation of Rab1A and IL4Rα remain largely unknown in gastric cancer. This study mainly to investigate the correlation between the expression of Rab1A and IL4Rα and the influence of Rab1A/IL4Rα on prognosis. In this study, we firstly performed the IHC staining to explore the expression of Rab1A and investigate the relationship between Rab1A expression and clinic-pathological factors. Our results showed Rab1A was highly expressed in gastric cancer tissues compared with the matched normal tissues. Furthermore, the subgroup analysis indicated that the expression of Rab1A in LNM group was obviously higher compared with the no-LNM group. And the TNM III group had a significantly higher expression of Rab1A compared with the other group. Besides, the results revealed Rab1A expression was closely related with LNM, Degree of differentiation, Venous invasion and TNM staging.
Previous study has reported that Rab1A overexpression led to a poor prognosis in CRC9,30,31, GC32 and intrahepatic cholangiocarcinoma19. Our results suggest that Rab1A positive group had a worse prognosis compared with the negative group in GC patient. Moreover, the subgroup analysis revealed Rab1A overexpression group had a poorer 5-year survival rate compared with the low-expression group in TNM I-II stating while no significant difference was obtained in TNM III stating, which indicated Rab1A played a crucial role on prognosis especially in TMN I-II staging.
Previous study reported that the expression of Rab1A and IL4Ra is highly correlated in lung cancer tissues, including the expression region and degree25. In our research, we firstly reported IL-4Rα was obviously elevated in GC tissues compared with the para-cancerous tissues. And the subgroup analysis based on different LNM and TNM staging indicated that IL-4Rα expression in LNM group was remarkably higher compared with the no-LNM group and the TNM III group had an apparently higher expression of IL-4Rα compared with the other group. Then the influence of IL-4Rα overexpression on prognosis was performed by the Kaplan-Meier analysis. The results revealed IL-4Rα overexpression led to a poor prognosis. And the subgroup analysis based on different TNM states revealed the group with high IL-4Rα expression had shorter five-year survival rates in both TNM I-II and TNM III.
We firstly checked the TCGA database via GEPIA platform to investigate the association of Rab1A and IL-4Rα expression. The results indicated Rab1A expression was closely related with the L-4Rα expression in GC tissues while no obvious correlation on expression was observed in para-cancer tissues. Then the IHC staining showed that Rab1A expression was remarkably associated with the expression of IL-4Rα in GC tissues. However, no significant difference was obtained in para-cancer tissues, which was consistent with the TGGA database. Finally, the qPCR was performed to investigate the Rab1A/IL-4Rα mRNA expression in 24 cases of tumor and normal tissue. Our results showed that the mRNA expression of Rab1A was closely related with the IL-4Rα mRNA expression in GC tumor tissues. In addition, the Kaplan-Meier analysis was performed to explore the influence of Rab1A/IL-4Rα overexpression on prognosis in GC patients. The results showed the both negative expression of Rab1A and IL-4Rα group had longer five-year survival rates compared with the other group. Besides, the both positive expression of Rab1A and IL-4Rα group had a worse prognosis compared with the other group. Finally, the nomograms predicting 3 and 5-year overall survival revealed that Rab1A/IL-4Rα expression played crucial roles in predicting the prognosis of GC patients. Thus, the Rab1A/ IL-4Rα may be applicated together in predicting patients’ prognosis as well as being tractable as novel targets in individualized therapy of GC.