Department of General Surgery, General Hospital of Central Theater Command, Wuhan, 430070, Hubei, China.
The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
Sci Rep. 2023 Sep 13;13(1):15144. doi: 10.1038/s41598-023-42060-x.
Family with sequence similarity three member (FAM3) plays a crucial role in the malignant development of various cancers of human. However, there remains doubtful what specific role of FAM3 family genes in pan-cancer. Our study aimed to investigate the role of FAM3 family genes in prognosis, immune subtype, tumor immune microenvironment, stemness score, and anticancer drug sensitivity of pan-cancer. We obtained data from UCSC Xena GDC and CellMiner databases, and used them to study the correlation of the expression, survival, immune subtype, tumor microenvironment, stemness score, and anticancer drug sensitivity between FAM3 family genes with pan-cancer. Furthermore, we investigated the tumor cellular functions and clinical prognostic value FAMC3 in pancreatic cancer (PAAD) using cellular experiments and tissue microarray. Cell Counting Kit-8 (CCK-8), transwell invasion, wound-healing and apoptosis assays were performed to study the effect of FAM3C on SW1990 cells' proliferation, migration, invasion and apoptosis. Immunohistochemical staining was used to study the relationship between FAM3C expression and clinical characteristics of pancreatic cancer patients. The results revealed that FAM3 family genes are significantly differential expression in tumor and adjacent normal tissues in 7 cancers (CHOL, HNSC, KICH, LUAD, LUSC, READ, and STAD). The expression of FAM3 family genes were negatively related with the RNAss, and robust correlated with immune type, tumor immune microenvironment and drug sensitivity. The expression of FAM3 family genes in pan-cancers were significantly different in immune type C1 (wound healing), C2 (IFN-gamma dominant), C3 (inflammatory), C4 (lymphocyte depleted), C5 (immunologically quiet), and C6 (TGF-beta dominant). Meanwhile, overexpression FAM3C promoted SW1990 cells proliferation, migration, invasion and suppressed SW1990 cells apoptosis. While knockdown of FAM3C triggered opposite results. High FAM3C expression was associated with duodenal invasion, differentiation and liver metastasis. In summary, this study provided a new perspective on the potential therapeutic role of FAM3 family genes in pan-cancer. In particular, FAM3C may play an important role in the occurrence and progression of PAAD.
家族与序列相似性 3 成员（FAM3）在各种人类癌症的恶性发展中起着至关重要的作用。然而，FAM3 家族基因在泛癌中的具体作用仍然存在疑问。我们的研究旨在探讨 FAM3 家族基因在泛癌中的预后、免疫亚型、肿瘤免疫微环境、干性评分和抗癌药物敏感性中的作用。我们从 UCSC Xena GDC 和 CellMiner 数据库中获取数据，并使用这些数据研究 FAM3 家族基因与泛癌之间的表达、生存、免疫亚型、肿瘤微环境、干性评分和抗癌药物敏感性的相关性。此外，我们使用细胞实验和组织微阵列研究了 FAMC3 在胰腺癌（PAAD）中的肿瘤细胞功能和临床预后价值。通过细胞计数试剂盒-8（CCK-8）、Transwell 侵袭、划痕愈合和凋亡实验研究 FAM3C 对 SW1990 细胞增殖、迁移、侵袭和凋亡的影响。免疫组织化学染色用于研究 FAM3C 表达与胰腺癌患者临床特征的关系。结果表明，在 7 种癌症（CHOL、HNSC、KICH、LUAD、LUSC、READ 和 STAD）的肿瘤和相邻正常组织中，FAM3 家族基因的表达存在显著差异。FAM3 家族基因的表达与 RNAss 呈负相关，与免疫类型、肿瘤免疫微环境和药物敏感性密切相关。在泛癌中，FAM3 家族基因的表达在免疫类型 C1（伤口愈合）、C2（IFN-γ优势）、C3（炎症）、C4（淋巴细胞耗竭）、C5（免疫安静）和 C6（TGF-β优势）中存在显著差异。同时，过表达 FAM3C 促进了 SW1990 细胞的增殖、迁移、侵袭，并抑制了 SW1990 细胞的凋亡。而敲低 FAM3C 则产生了相反的结果。FAM3C 高表达与十二指肠浸润、分化和肝转移有关。总之，本研究为 FAM3 家族基因在泛癌中的潜在治疗作用提供了新的视角。特别是，FAM3C 可能在 PAAD 的发生和发展中发挥重要作用。
