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.
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β1（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，并在各种癌症类型中异常表达。但是,SPTBN1在泛癌症中的确切作用尚不清楚.本报告旨在显示SPTBN1在人类癌症中的表达模式和预后状况，并进一步评估其在肾肾癌（KIRC）和葡萄膜黑色素瘤（UVM）中的预后/治疗价值和免疫学作用。
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情况。通过R包和TIMER2.0平台进一步研究了KIRC和UVM中SPTBN1表达与生存/肿瘤免疫之间的关系。还通过R软件探讨了SPTBN1在KIRC和UVM中的治疗作用。在此之后,在我们的癌症患者和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：总体而言，癌组织中经常有较低的SPTBN1表达水平，与邻近的非肿瘤患者相比。SPTBN1表达通常对泛癌症患者的生存有不同的影响；SPTBN1的上调对KIRC个体的生存有保护作用。这与在UVM患者中发现的情况相反。在KIRC，SPTBN1表达与肿瘤前免疫细胞浸润之间存在显著负相关,包括Treg细胞,Th2细胞，单核细胞和M2-巨噬细胞，和免疫调节剂基因的表达，如肿瘤坏死因子超家族成员9（TNFSF9）；而，在UVM中，这些相关性表现出相反的模式。我们的癌症队列和GEO数据库中的以下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KIRC的免疫治疗耐药，以及UVM中抗癌靶向治疗的增强。
结论：当前的研究提供了令人信服的证据，表明SPTBN1可能是KIRC和UVM的新型预后和治疗相关生物标志物，为抗癌策略提供新的思路。
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情况。通过R包和TIMER2.0平台进一步研究了KIRC和UVM中SPTBN1表达与生存/肿瘤免疫之间的关系。还通过R软件探讨了SPTBN1在KIRC和UVM中的治疗作用。在此之后,在我们的癌症患者和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：总体而言，癌组织中经常有较低的SPTBN1表达水平，与邻近的非肿瘤患者相比。SPTBN1表达通常对泛癌症患者的生存有不同的影响；SPTBN1的上调对KIRC个体的生存有保护作用。这与在UVM患者中发现的情况相反。在KIRC，SPTBN1表达与肿瘤前免疫细胞浸润之间存在显著负相关,包括Treg细胞,Th2细胞，单核细胞和M2-巨噬细胞，和免疫调节剂基因的表达，如肿瘤坏死因子超家族成员9（TNFSF9）；而，在UVM中，这些相关性表现出相反的模式。我们的癌症队列和GEO数据库中的以下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KIRC的免疫治疗耐药，以及UVM中抗癌靶向治疗的增强。
结论：当前的研究提供了令人信服的证据，表明SPTBN1可能是KIRC和UVM的新型预后和治疗相关生物标志物，为抗癌策略提供新的思路。
