Novel Implication of the Basement Membrane for Breast Cancer Outcome and Immune Infiltration

Abstract

Therapeutic failure in breast cancer patients is largely attributed to postoperative advancement and therapy resistance. Nevertheless, an efficacious prognostic signature for recognizing this population is lacking. The basement membrane (BM) has been proven to be strongly involved in cancer progression and metastasis, and has the potential to be a powerful predictor in breast cancer. In this study, substantial bulk RNA transcriptomics, single cell RNA transcriptomics and clinical information were collected from TCGA-BRCA, METABRIC and GSE96058, and Kaplan-Meier survival curves, single cell analysis and in vitro experiments were conducted to validate the signature. From the results, a prognostic index, namely, the BMscore, was established with six pivotal BM genes, specifically LOXL1, FBLN1, FBLN5, SDC1, ADAMTS8 and PXDNL. Verification by independent cohorts showed that breast cancer patients with high BMscore had a distinctly worse outcome. By integrating the BMscore and clinical factors, we constructed a prognostic nomogram that displayed good predictive capability. Furthermore, we evaluated the implication of the BMscore in breast cancer immune infiltration. More importantly, a strongly positive correlation between the BMscore and EMT activity was revealed with immunohistochemistry and in vitro experiments. Taken together, we provided a novel BMscore gene signature for breast cancer patients to predict clinical prognosis and metastasis accurately, which may help with individualized clinical decision-making.

Identification of a PANoptosis-related Gene Signature for Predicting the Prognosis, Tumor Microenvironment and Therapy Response in Breast Cancer

“…In addition, the ROC and calibration curves of the external validation cohort further confirmed the significant predictive value of our model (Figure 2 G, H). Taken together, these results demonstrated the outstanding performance of our nomogram compared with previously established prognostic models 43 - 45 .…”

“…Recently, several models have been developed to predict the prognosis of BC patients. Tian et al have built a prognostic model using basement membrane-related genes 43 . Cui et al have also established a nomogram based on nicotinamide metabolism-related signature 44 , while Li's model was constructed utilizing m6A-related genes 45 .…”

Identification of a basement membrane gene signature for predicting prognosis and estimating the tumor immune microenvironment in prostate cancer

“…BMGs may be predominantly expressed in stromal cells, particularly in cells involved in the production and maintenance of the basement membrane, such as fibroblasts and myoepithelial cells. These cells synthesize and secrete matrix components, forming the structure of the basement membrane [ 7 , 8 ]. However, Laminin-511 has been implicated in cell migration, tumor growth, and metastasis, with higher levels of this isoform found in many breast, lung, thyroid, and prostate cancers [ 9 , 10 ].…”

Identification of a basement membrane-related genes signature to predict prognosis, immune landscape and guide therapy in gastric cancer

“…[11] Recent studies have reported that basement membranes interact with the immune microenvironment to promote tumor progression. [12] As of now, prognostic features related to the basement membrane have been established with high predictive accuracy in liver cancer, [13] breast cancer, [14] and lung adenocarcinoma. [15] However, research in this area regarding gastric cancer (GC) is limited.…”

“…As of now, prognostic features related to the basement membrane have been established with high predictive accuracy in liver cancer, [ 13 ] breast cancer, [ 14 ] and lung adenocarcinoma. [ 15 ] However, research in this area regarding gastric cancer (GC) is limited.…”