High expression of COL6A1 predicts poor prognosis and response to immunotherapy in bladder cancer

Abstract

Extracellular matrix (ECM), as an important framework for tumor microenvironment, plays important roles in many critical processes, including tumor growth, invasion, immune suppression, and drug resistance. However, few biomarkers of ECM-related genes (ERGs) have been developed for prognosis prediction and clinical treatment of bladder cancer (BC) patients. Bioinformatics analysis and LC-MS/MS analysis were used to screen differentially expressed ERGs in BC. Multivariate Cox regression analysis and Lasso regression analysis were used to construct and validate an ERGs-based prognostic prediction model for BC. Immunohistochemistry was used to detect the protein expression of hub gene-COL6A1 in BC patients. Using bioinformatics analysis from The Cancer Genome Atlas (TCGA) database and proteomic analysis from our BC cohort, we constructed and validated an effective prognostic prediction model for BC patients based on four differentially expressed ERGs (MAP1B, FBN1, COL6A1, and MFAP5). Moreover, we identified human collagen VI-COL6A1 was a hub gene in this prognostic prediction model and found that COL6A1 was closely related to malignancy progression, prognosis, and response to PD-1 inhibitor immunotherapy in BC. Our findings highlight the satisfactory predictive value of ECM-related prognostic models in BC and suggested that COL6A1 may be a potential biomarker in predicting malignant progression, prognosis, and efficacy of immunotherapy in BC.

Identification and validation of a signature based on myofibroblastic cancer-associated fibroblast marker genes for predicting prognosis, immune infiltration, and therapeutic response in bladder cancer

“…Our previous research also demonstrated the relationship between COL6A1 expression and the efficacy of immunotherapy [ 23 ]. This was in addition to validating the relationship between MAP1B expression, another key gene in our signature, and immunotherapy efficacy, by IHC.…”

“…COL6A1 (collagen type VI) is one of the most important extracellular matrix proteins that plays a crucial role in the TME while also being involved in the growth, proliferation, and metastasis of malignancies [ 22 ]. According to earlier research, high COL6A1 expression has been linked to poor prognosis and metastasis in cervical, prostate, bladder, lung, and pancreatic cancers [ 23 24 25 26 27 ]. MAP1B (microtubule-associated protein 1B) is a major cytoskeletal protein closely associated with neuronal growth and differentiation [ 28 ].…”

The role of lactate metabolism-related LncRNAs in the prognosis, mutation, and tumor microenvironment of papillary thyroid cancer

“…It has been reported that extracellular matrix signaling protein ADAM22 can facilitate distant disease spread in vivo and is a crucial mechanism in the metastasis of breast cancer ( 69 ). High expression of ECM-related gene COL6A1 predicts poor prognosis and poor immunotherapy response in bladder cancer ( 70 ). Overall, there are altered expression patterns of extracellular matrix-associated genes in metastatic cancers, and extracellular matrix-associated genes are expected to be markers of aggressive, growing tumors.…”

Role of the tumour microenvironment in bladder cancer pathogenesis and value of the reverse translational approach: a tale of two species

“…In another study, proteomic analysis of an extracellular matrix (ECM)‐related gene, COL6A1, was identified in human bladder cancer tissue samples, and an increased expression of COL6A1 was correlated with lower survival rate, metastasis and poor response to PD‐1 inhibitor immunotherapy in those patients 123 . COL6A1 is one of the main proteins that participate in the ECM construction leading to the tumour escaping immune mechanisms, metastasis, tumour cell growth and progression 124 .…”

“…In another study, proteomic analysis of an extracellular matrix (ECM)-related gene, COL6A1, was identified in human bladder cancer tissue samples, and an increased expression of COL6A1 was correlated with lower survival rate, metastasis and poor response to PD-1 inhibitor immunotherapy in those patients. 123 COL6A1 is one of the main proteins that participate in the ECM construction leading to the tumour escaping immune mechanisms, metastasis, tumour cell growth and progression. 124 Moreover, COL6A1 can participate in a cascade of downstream intracellular signalling pathways, including the Janus kinase-signal transducers and activators of transcription (JAK-STAT) Kinase signalling pathway and vascular endothelial growth factor (VEGF) signalling pathway, which promote further tumour progression and metastasis.…”