A Prognostic Signature Consisting of Pyroptosis-Related Genes and SCAF11 for Predicting Immune Response in Breast Cancer

Abstract

Pyroptosis, characterized as an inflammasome-mediated cell death pathway, may be participated in tumorigenesis and progression. However, the underlying molecular function and mechanism of pyroptosis in BRCA remain unclear. In our study, we aimed to develop a prognostic signature in BRCA based on pyroptosis-associated genes. Data was downloaded from TCGA database, and then we screened 760 female BRCA samples and 104 normal breast tissues as the training set. Seven pyroptosis-related genes (CASP9, GPX4, IL18, NLRC4, SCAF11, TIRAP, and TNF) were identified as the pyroptosis-related prognostic model for BRCA using LASSO Cox regression. We subsequently tested the prognostic value of pyroptosis-associated gene signature in a validation set, GSE 20685. Time-dependent receiver operating characteristic analysis demonstrated the credible predictive capacity of this pyroptosis-associated gene signature. The area under the curves were 0.806 at 3 years, 0.787 at 5 years, 0.775 at 8 years, and 0.793 at 10 years in the training set, and 0.824 at 5 years, 0.808 at 8 years, and 0.790 at 10 years in the validation set. Furthermore, there are currently few data on SCAF11 regulating pyroptosis. To clarify this issue, we performed integrative bioinformatics and experimental analysis. Knocking down SCAF11 possessed an anti-cancer effect in terms of inhibiting cell viability and suppressing colony-formation in in-vitro functional assays. Meanwhile, the biological functions of SCAF11 in BRCA were further validated with several algorithms, such as Xiantao tool, LinkedOmics, GEPIA2, and TISIDB. These findings indicated that the expression of SCAF11 was significantly correlated with diverse tumor-infiltrating lymphocytes (TILs), including T central memory cell (Tcm), and type 2 T helper cell (Th2), etc. Functional enrichment analysis suggested that co-expression genes of SCAF11 primarily participated in inflammation and immune-related signaling pathways, such as oxidative phosphorylation, antimicrobial humoral response, and immunoglobulin complex. Moreover, SCAF11 expression was positively correlated with several immune checkpoints, including PD-L1, B7H3, and PDCD1LG2. Taken together, this study uncovered that pyroptosis-associated gene signature might be applied as an effective independent predictor in patients with BRCA. The pyroptosis-related gene SCAF11 might play potential roles in the regulation of immune microenvironment in BRCA.

The cuproptosis-related signature predicts prognosis and indicates immune microenvironment in breast cancer

“…To further explore the predictive ability of our signature, a comparison was performed among several significant molecular signatures employed for predicting OS in patients with BC. Compared with the other signature, such as ferroptosis, necroptosis, pyroptosis, and immune-related ( Lin et al, 2020 ; Zhong et al, 2020 ; Wang et al, 2021a ; Wu et al, 2021a ; Zhu et al, 2021b ; Ding et al, 2021 ; Ye et al, 2021 ; Lu et al, 2022a ; Lu et al, 2022b ; Chen et al, 2022 ; Chu et al, 2022 ; Yu et al, 2022 ; Zou et al, 2022 ), our signature indicated much higher AUCs, which indicated a better predictive ability, especially in predicting the long-term survival status. Furthermore, we constructed a prognostic nomogram that could simplify treatment decision-making for patients with BC.…”

“…In our study, the AUCs of the signatures at 3-, 5-, and 10-year were 0.683, 0.640, and 0.794, respectively, significantly higher than most hallmark predictive models. Table 1 showed that the 3-, 5-, and 10-year AUCs of the other four prognostic signatures, namely, the 9 ferroptosis-related gene signature (3-, 5-, and 10-year AUCs: 0.713, 0.713, and 0.684) ( Lu et al, 2022a ), 4 immune-related gene signature (3-, 5-, and 10-year AUCs: 0.692, 0.691, and 0.715) ( Ding et al, 2021 ), 7 pyroptosis-related gene signature (3-, 5-, and 10-year AUCs: 0.785, 0.769, and 0.711) ( Chu et al, 2022 ), and 6 autophagy-related gene signature (3-, 5-, and 10-year AUCs: 0.640, 0.600, and 0.610) ( Zhong et al, 2020 ) were comparable to the predictive capabilities of our predictive model, and our signature stand out with a clear advantage in predicting the long-term survival of BC patients, with a 10-year AUC of 0.819. We also listed the other signatures that focus more on short-term survival, such as 1-year, 2-year, 3-year, and 5-year survival.…”

A novel prognostic model based on pyroptosis-related genes for multiple myeloma

“…SCAF11, also known as caspase-11, is a pro-in ammatory enzyme, which may have a role in cancer-associated angiogenesis [51]. Chu et al demonstrated that knocking down SCAF11 suppressed cell proliferation and colony formation in breast cancer cell lines [52].…”

ALKBH family members as novel biomarkers and prognostic factors in human breast cancer

“…XianTao aims to provide users with a better understanding of gene interpretation, and enrichment results to the researcher (https://www.xiantao.love) [48][49][50]. In this study, we get several enrichment pathways associated with the ALKBH family in breast cancer disease from the database.…”