Identification of an Aging-Related Gene Signature in Predicting Prognosis and Indicating Tumor Immune Microenvironment in Breast Cancer

Abstract

Breast cancer (BC) is the most commonly diagnosed malignancy accompanied by high invasion and metastasis features. Importantly, emerging studies have supported that aging is a key clue that participates in the immune state and development of BC. Nevertheless, there are no studies concerning the aging-related genes (AGs) in constructing the prognosis signature of BC. Here, to address this issue, we initially performed a systematic investigation of the associations between AGs and BC prognosis and accordingly constructed a prognosis risk model with 10 AGs including PLAU, JUND, IL2RG, PCMT1, PTK2, HSPA8, NFKBIA, GCLC, PIK3CA, and DGAT1 by using the least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis. Meanwhile, our analysis further confirmed that the nomogram possessed a robust performance signature for predicting prognosis compared to clinical characteristics of BC patients, including age, clinical stage, and TNM staging. Moreover, the risk score was confirmed as an independent prognostic index of BC patients and was potentially correlated with immune scores, estimate score, immune cell infiltration level, tumor microenvironment, immunotherapy effect, and drug sensitivity. Furthermore, in the external clinical sample validation, AGs were expressed differentially in patients from different risk groups, and tumor-associated macrophage markers were elevated in high-risk BC tissues with more co-localization of AGs. In addition, the proliferation, transwell, and wound healing assays also confirmed the promoting effect of DGAT1 in BC cell proliferation and migration. Therefore, this well-established risk model could be used for predicting prognosis and immunotherapy in BC, thus providing a powerful instrument for combating BC.

Construction and validation of an aging-related gene signature predicting the prognosis of pancreatic cancer

“…The ARGs that overlap our prognostic model with its model are PLAU and TOP2A. In addition, PLAU has predictive value as ARG in breast cancer, lung square cancer, head and neck square cell cancer, etc (Yang et al, 2020;Lv et al, 2021;Zhai et al, 2022). TOP2A can predict the prognosis of hepatocellular carcinoma (Cai et al, 2022).…”

Construction and validation of an aging‐related gene signature for prognosis prediction of patients with breast cancer

“…Therefore, exploring prognostic signature of ARG is vital to understand the function of aging process in BC. There are currently two studies similar to ours, 14 , 15 The difference in method was that the ARGs we used to construct the signature were associated with survival overlapped both in the TCGA training set and the GEO validation set, and this method was the most accurate and convincing, while the other two study was only used the TCGA training set to construct the signature which were differed from the method of our study. And our study closely linked prognostic signature to immune, clinical treatment (including chemotherapy, immunotherapy, and targeted therapy) to elaborate the associations with clincal traits, the other two studies were not sufficiently linked to clinical treatment.…”

A Novel Aging-Related Prognostic lncRNA Signature Correlated with Immune Cell Infiltration and Response to Immunotherapy in Breast Cancer

“…Aging is an independent risk factor for some cancers [24]. In addition, aging-related markers have prognostic potential for predicting cancer [27]. The above facts indicated that we urgently need to identify more aging-related molecular markers in BC patients.…”

“…In previous studies, some aging-related molecular markers that can predict invasive BC have been verified [27], but the utilization of aging-related lncRNAs in BRCA has not been presented. We utilized many samples in the TCGA and GEO databases to identify and validate the risk model, which can predict the survival, pathological characteristics, and treatment methods of BC patients well, thereby providing powerful guidance for clinical practice.…”