Zhang Tianhao, Lai Shurong, Cai Yuzhi, Huang Zhixin, Li Ying, Chen Sile, Zhang Zhimei, Ye Zhijun, Lai Xiaoling, Zhai Ertao, Cai Shirong, Chen Jianhui
Center of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Gastric Cancer Center, Sun Yat-sen University, Guangzhou, China.
Front Cell Dev Biol. 2021 Nov 19;9:719613. doi: 10.3389/fcell.2021.719613. eCollection 2021.
Gastric cancer (GC) is one of the most common and poor prognosis malignancy in the world. The Family with sequence similarity 83 (FAM83) comprises of eight members of A-H. Accumulating evidence confirmed important roles for FAM83 family in tumorigenesis and progression. However, the prognostic values of FAM83 family in GC still have not been clarified. ONCOMINE, UALCAN, GEPIA, THE HUMAN PROTEIN ATLAS, Kaplan-Meier Plotter, cBioPortal, DAVID, STRING and TIMER databases and R software were adopted in this study. In this study, we demonstrated that the mRNA levels of FAM83 B/C/D/H were significantly up-regulated in stomach adenocarcinoma (STAD), but the protein level of FAM83G/H were remarkable lowly in STAD. Next, FAM83C/D/G/H were significantly associated with tumor stages in STAD patients. Then, the mutation rate of FAM83 family members in STAD patients was 46%, and the highest mutation rate was FAM83H (23%). Furthermore, the functions of FAM83 family and their 259 co-expression genes were primarily related to Shigellosis, RNA degradation and Ribosome biogenesis in eukaryotes pathway. Besides, we have established the prognostic model of FAM83 family in STAD, including the prognostic model of STAD patients (FAM83C/D/G), STAD with lymph node metastasis (FAM83C/D/G/H) and STAD with ERBB2 high expression (FAM83G/H). FAM83C/D high expression with a poor prognosis, while FAM83G/H high expression with a favorable prognosis of STAD. Additionally, we found that the expression of FAM83C/D/G/H were significantly correlated with the infiltration of six types of immune cells [B cells, CD8T cells, CD4T cells, macrophages and Myeloid dendritic cells (DC)], whereas CD4T cells and Macrophage cells have higher risk scores (HR > 1) when FAM83C lowly expression and FAM83D highly expression. The risk score of NK cells was significantly reduced when FAM83G lowly expression and FAM83H highly expression (HR < 1). These findings suggested that FAM83C/D/G/H might play key roles in STAD tumorigenesis and progression, and FAM83C/D might be risk factors but FAM83G/H might be favorable prognostic factors for STAD patients. In addition, CD4T cells and Macrophage cells may be the promoters of FAM83D in progression of STAD, while NK cells may promote the protective effect of FAM83H on STAD patients.
胃癌（GC）是世界上最常见且预后较差的恶性肿瘤之一。序列相似性家族83（FAM83）由A - H八个成员组成。越来越多的证据证实FAM83家族在肿瘤发生和发展中起重要作用。然而，FAM83家族在GC中的预后价值仍未阐明。本研究采用了ONCOMINE、UALCAN、GEPIA、人类蛋白质图谱、Kaplan - Meier Plotter、cBioPortal、DAVID、STRING和TIMER数据库以及R软件。在本研究中，我们发现FAM83 B/C/D/H的mRNA水平在胃腺癌（STAD）中显著上调，但FAM83G/H的蛋白水平在STAD中显著降低。接下来，FAM83C/D/G/H与STAD患者的肿瘤分期显著相关。然后，STAD患者中FAM83家族成员的突变率为46%，其中FAM83H的突变率最高（23%）。此外，FAM83家族及其259个共表达基因的功能主要与志贺氏菌病、RNA降解和真核生物中的核糖体生物发生途径有关。此外，我们建立了FAM83家族在STAD中的预后模型，包括STAD患者（FAM83C/D/G）、有淋巴结转移的STAD（FAM83C/D/G/H）和ERBB2高表达的STAD（FAM83G/H）的预后模型。FAM83C/D高表达提示STAD预后不良，而FAM83G/H高表达提示STAD预后良好。此外，我们发现FAM83C/D/G/H的表达与六种免疫细胞（B细胞、CD8T细胞、CD4T细胞、巨噬细胞和髓样树突状细胞（DC））的浸润显著相关，而当FAM83C低表达和FAM83D高表达时，CD4T细胞和巨噬细胞的风险评分较高（HR > 1）。当FAM83G低表达和FAM83H高表达时，NK细胞的风险评分显著降低（HR < 1）。这些发现表明FAM83C/D/G/H可能在STAD的肿瘤发生和发展中起关键作用，FAM83C/D可能是危险因素，而FAM83G/H可能是STAD患者的良好预后因素。此外，CD4T细胞和巨噬细胞可能是FAM83D在STAD进展中的促进因素，而NK细胞可能促进FAM83H对STAD患者的保护作用。
