LCK

Overview

LCK (Lymphocyte Cell-Specific Protein-Tyrosine Kinase) is a Src-family tyrosine kinase expressed predominantly in T lymphocytes and is critical for T-cell receptor signalling. In cutaneous melanoma, high LCK protein expression marks the immune transcriptomic subclass and, together with pathology-derived lymphocyte score (LScore), constitutes a powerful independent prognostic biomarker for patients with regional metastatic disease.

Alterations observed in the corpus

  • High LCK protein expression (by RPPA) identifies the immune transcriptomic subclass in cutaneous melanoma (TCGA 333-sample multi-platform cohort); independent favourable prognostic marker in stage III (regional metastasis) patients. PMID:26091043
  • A bivariate model of pathology-derived LScore + RPPA LCK expression predicts survival in stage III melanoma (HR = 5.5 for both-high vs. both-low; log-rank p = 7.9eā€“5); both features are independent in multivariable Cox regression. PMID:26091043

Cancer types (linked)

  • SKCM: High LCK protein expression is the defining molecular feature of the immune transcriptomic subclass; associated with improved survival in regional-metastatic (stage III) melanoma; authors propose integration into future AJCC staging and adjuvant-therapy frameworks. PMID:26091043

Co-occurrence and mutual exclusivity

  • High LCK expression contrasts with SYK (also high in immune subclass but not prognostic), suggesting T-cell (LCK) rather than B-cell (SYK) signalling drives the immune-subtype survival benefit. PMID:26091043

Therapeutic relevance

  • LCK expression proposed as a component of a prognostic/predictive biomarker (with LScore) for adjuvant therapy decisions in stage III melanoma; immune subclass also shows highest PD-L1/PD-1 expression, linking LCK-high tumours to checkpoint-blockade biomarker hypothesis. PMID:26091043

Open questions

  • The bivariate LScore + LCK model requires prospective validation in checkpoint-blockade trials; whether LCK-high tumours are uniquely responsive to pembrolizumab/nivolumab/ipilimumab remains untested in this dataset. PMID:26091043

Sources

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