KRT6A
Overview
KRT6A (Keratin 6A) encodes a type II intermediate filament protein expressed in stratified epithelia, characteristic of squamous differentiation. In bladder cancer, KRT6A is a defining marker of basal/stem identity within the basal-squamous mRNA subtype of muscle-invasive bladder cancer (MIBC), which represents 35% of tumors and is enriched for squamous features and immune infiltration.
Alterations observed in the corpus
- Defining basal/stem marker of the basal-squamous MIBC subtype (35% of 412 tumors, TCGA BLCA 2017); high expression co-occurs with CD44, KRT5, and KRT14 in squamous-differentiated tumors with strongest immune signature. PMID:28988769
- Specifically among 37/45 squamous-feature tumors that fell in the basal-squamous subtype (p < 10⁻¹¹). PMID:28988769
Cancer types (linked)
- Bladder Urothelial Carcinoma (BLCA): KRT6A is a key marker of the basal-squamous subtype, which has high CD274 and CTLA4 expression, strong immune infiltrate, and is potentially responsive to both cisplatin-based neoadjuvant chemotherapy and immune checkpoint therapy. PMID:28988769
Co-occurrence and mutual exclusivity
- Co-expressed with CD44, KRT5, and KRT14 as defining basal-squamous markers in MIBC. PMID:28988769
- Mutually low vs. luminal markers KRT20, UPK1A, UPK2 in the umbrella-cell luminal subtype. PMID:28988769
Therapeutic relevance
- The basal-squamous MIBC subtype (defined in part by KRT6A expression) is proposed as an indication for both cisplatin-based neoadjuvant chemotherapy and immune checkpoint therapy (e.g., atezolizumab); head-to-head trials are warranted. PMID:28988769
Open questions
- Whether KRT6A expression level itself (beyond subtype membership) has independent prognostic or predictive value in MIBC has not been demonstrated in this cohort. PMID:28988769
Sources
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