AUTHOR=Xie Rongrong , Yuan Mengping , Jiang Yiyan 

TITLE=The Pan-Cancer Crosstalk Between the EFNA Family and Tumor Microenvironment for Prognosis and Immunotherapy of Gastric Cancer

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.790947

DOI=10.3389/fcell.2022.790947

ISSN=2296-634X

ABSTRACT=EFNA1–5 have important physiological functions in regulating tumorigenesis and metastasis. However, correlating EFNA genes in the TIME and the prognosis of patients with gastric cancer remains to be determined.The expression of EFNA1–5 in pan-cancer and gastric cancer was comprehensively analyzed using UCSC Xena, the Oncomine dataset, and UALCAN. We further completed survival analysis by Kaplan-Meier plotter to evaluate the prognosis of the high and low expression groups of the EFNA genes in patients with gastric cancer. The TIMER was used to reveal the correlation between immune cell infiltration and genes of interest. Spearman correlation was used to find an association between the EFNA genes and tumor stem cells, TIME, MSI, or TMB. We also used cBioportal, GeneMANIA, and STRINGS to explore the types of changes in these genes and the protein interactions. Finally, we described the TIME, predicted the relationship between the EFNA genes and IC50, and analyzed the relationship between the EFNA family genes and immune checkpoints.The expression of EFNA1, EFNA3-5 was elevated in pan-cancer. Compared with normal adjacent tissues, EFNA1, EFNA3-4 were up-regulated in gastric cancer. In terms of the influence on the survival of patients, the expression of EFNA3-4 were related to OS and DFS for patients with gastric cancer. High expression of EFNA5 often predicted poor OS and DFS. In gastric cancer, the expression of EFNA3 and EFNA4 showed a significant negative correlation with B cells. The higher the expression of EFNA5, the higher the abundance of B cells, CD4+ T cells, and macrophages. CD8+ T cells, dendritic cells infiltration, and EFNA1–4 expression was negatively correlated. The infiltration of CD4+ T cells, macrophages, and neutrophils was negatively correlated with the expression of EFNA1, EFNA3-4. TMB and MSI were positively correlated with EFNA-4 expression. In the tumor microenvironment and drug sensitivity, EFNA3-5 also showed a significant correlation. In addition, we explored the relationship between the EFNA family genes and the immune microenvironment ,immune checkpoints, and IC50 of 5-fluorouracil, cisplatin, docetaxel, and gemcitabine.Our study provides new ideas for tumor treatment and prognosis from the perspective of TIME, and nominates EFNA1–5 to become potential therapeutic targets for gastric cancer.