非红细胞 spectrin Beta 1（SPTBN1）在人肾透明细胞癌和葡萄膜黑素瘤中的临床意义：基于泛癌分析的研究。

Clinical significance of nonerythrocytic spectrin Beta 1 (SPTBN1) in human kidney renal clear cell carcinoma and uveal melanoma: a study based on Pan-Cancer Analysis.

机构信息

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, Guangdong, China.

Department of Research and Molecular Diagnostics, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, Guangdong, China.

出版信息

BMC Cancer. 2023 Apr 3;23(1):303. doi: 10.1186/s12885-023-10789-3.

DOI:10.1186/s12885-023-10789-3

PMID:37013511

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10071745/

Abstract

BACKGROUND

Nonerythrocytic spectrin beta 1 (SPTBN1) is an important cytoskeletal protein that involves in normal cell growth and development via regulating TGFβ/Smad signaling pathway, and is aberrantly expressed in various cancer types. But, the exact role of SPTBN1 in pan-cancer is still unclear. This report aimed to display expression patterns and prognostic landscapes of SPTBN1 in human cancers, and further assess its prognostic/therapeutic value and immunological role in kidney renal carcinoma (KIRC) and uveal melanoma (UVM).

METHODS

We firstly analyzed expression patterns and prognostic landscapes of SPTBN1 in human cancers using various databases and web-based tools. The relationships between SPTBN1 expression and survival/tumor immunity in KIRC and UVM were further investigated via R packages and TIMER 2.0 platform. The therapeutic roles of SPTBN1 in KIRC and UVM were also explored via R software. Following this, the prognostic value and cancer immunological role of SPTBN1 in KIRC and UVM were validated in our cancer patients and GEO database.

RESULTS

Overall, cancer tissue had a lower expression level of SPTBN1 frequently in pan-cancer, compared with those in adjacent nontumor one. SPTBN1 expression often showed a different effect on survival in pan-cancer; upregulation of SPTBN1 was protective to the survival of KIRC individuals, which was contrary from what was found in UVM patients. In KIRC, there were significant negative associations between SPTBN1 expression and pro-tumor immune cell infiltration, including Treg cell, Th2 cell, monocyte and M2-macrophage, and expression of immune modulator genes, such as tumor necrosis factor superfamily member 9 (TNFSF9); while, in UVM, these correlations exhibited opposite patterns. The following survival and expression correlation analysis in our cancer cohorts and GEO database confirmed these previous findings. Moreover, we also found that SPTBN1 was potentially involved in the resistance of immunotherapy in KIRC, and the enhance of anti-cancer targeted treatment in UVM.

CONCLUSIONS

The current study presented compelling evidence that SPTBN1 might be a novel prognostic and therapy-related biomarker in KIRC and UVM, shedding new light on anti-cancer strategy.

摘要

背景

非红细胞血影蛋白β 1（SPTBN1）是一种重要的细胞骨架蛋白，通过调节 TGFβ/Smad 信号通路参与正常细胞的生长和发育，在各种癌症类型中异常表达。但是，SPTBN1 在泛癌中的确切作用仍不清楚。本报告旨在展示 SPTBN1 在人类癌症中的表达模式和预后特征，并进一步评估其在肾透明细胞癌（KIRC）和葡萄膜黑色素瘤（UVM）中的预后/治疗价值和免疫作用。

方法

我们首先使用各种数据库和基于网络的工具分析了 SPTBN1 在人类癌症中的表达模式和预后特征。通过 R 包和 TIMER 2.0 平台进一步研究了 SPTBN1 表达与 KIRC 和 UVM 中生存/肿瘤免疫的关系。我们还通过 R 软件探索了 SPTBN1 在 KIRC 和 UVM 中的治疗作用。之后，我们在癌症患者和 GEO 数据库中验证了 SPTBN1 在 KIRC 和 UVM 中的预后价值和癌症免疫学作用。

结果

总的来说，与相邻的非肿瘤组织相比，泛癌组织中 SPTBN1 的表达水平通常较低。SPTBN1 的表达在泛癌中对生存的影响往往不同；在 KIRC 患者中，SPTBN1 的上调对生存有保护作用，而在 UVM 患者中则相反。在 KIRC 中，SPTBN1 的表达与促肿瘤免疫细胞浸润呈显著负相关，包括调节性 T 细胞、Th2 细胞、单核细胞和 M2 巨噬细胞，以及免疫调节剂基因如肿瘤坏死因子超家族成员 9（TNFSF9）的表达；而在 UVM 中，这些相关性则呈现相反的模式。我们在癌症队列和 GEO 数据库中的生存和表达相关性分析证实了这些先前的发现。此外，我们还发现 SPTBN1 可能参与了 KIRC 中免疫治疗的耐药性，以及 UVM 中抗癌靶向治疗的增强。