Expression and serum levels of the neural cell adhesion molecule L1-like protein (CHL1) in gastrointestinal stroma tumors (GIST) and its prognostic power

Abstract

Introduction: Diagnosis of gastrointestinal stroma tumors (GIST) is based on the histological evaluation of tissue specimens. Reliable systemic biomarkers are lacking. We investigated the local expression of the neural cell adhesion molecule L1-like protein (CHL1) in GIST and determined whether soluble CHL1 proteoforms could serve as systemic biomarkers. Material and Methods: Expression of CHL1 was analyzed in primary tumor specimens and metastases. 58 GIST specimens were immunohistochemically stained for CHL1 on a tissue microarray (TMA). Systemic CHL1 levels were measured in sera derived from 102 GIST patients and 91 healthy controls by ELISA. Results were statistically correlated with clinicopathological parameters. Results: CHL1 expression was detected in GIST specimens. Reduced tissue expression was significantly associated with advanced UICC stages (p = 0.036) and unfavorable tumor localization (p = 0.001). CHL1 serum levels are significantly elevated in GIST patients (p < 0.010). Elevated CHL1 levels were significantly associated with larger tumors (p = 0.023), advanced UICC stage (p = 0.021), and an increased Fletcher score (p = 0.041). Moreover, patients with a higher CHL1 serum levels displayed a significantly shortened recurrence free survival independent of other clinicopathological variables. Conclusion: Local CHL1 expression and serum CHL1 levels show a reverse prognostic behavior, highlighting the relevance of proteolytic shedding of the molecule. The results of the study indicate a potential role of serum CHL1 as a diagnostic and prognostic marker in GIST.

Interplay in neural functions of cell adhesion molecule close homolog of L1 (CHL1) and Programmed Cell Death 6 (PDCD6)

“…[62][63][64][65] Reduced tissue expression and enhanced serum levels of CHL1 in gastrointestinal stroma tumors correlate with advances of tumor stages and shorter recurrence-free survival. 66 CHL1 also promotes cell proliferation, and metastasis of human glioma cells both in vitro and in vivo, and CHL1 expression is upregulated in glioblastoma cells. 67 Interestingly, in xenograft tumors in nude mice, administration of siRNA targeting CHL1 not only downregulates CHL1 expression in vivo, but also upregulates activated caspase-3 levels.…”

“…It is a tumor suppressor in many tumors, such as neuroblastoma, nasopharyngeal carcinoma, esophageal squamous cell carcinoma, and non‐small cell lung cancer 62–65 . Reduced tissue expression and enhanced serum levels of CHL1 in gastrointestinal stroma tumors correlate with advances of tumor stages and shorter recurrence‐free survival 66 . CHL1 also promotes cell proliferation, and metastasis of human glioma cells both in vitro and in vivo, and CHL1 expression is upregulated in glioblastoma cells 67 .…”

Improved understanding of gastrointestinal stromal tumors biology as a step for developing new diagnostic and therapeutic schemes (Review)

“…GIST expresses CHL1 on mRNA as well as on protein level. Moreover, systemic CHL1 levels are increased in patients with GIST and is associated with a shortened RFS, regardless of other clinicopathological parameters (47).…”

Biodiversity and Conservation of Fish in the Beibu Gulf

“…It performs similar physiological activities in neural system development as CHL1 (Borghesi and Milcarek, 2006). CHL1 is produced as two isoforms, and isoform two is distinguished by the presence of an extra miniexon 8 (Karstens et al, 2020). These isoforms have no physiological significance.…”