CHGA

Overview

CHGA (chromogranin A) is a neuroendocrine secretory protein widely used as a marker of neuroendocrine differentiation. In neuroblastoma single-cell transcriptomics, CHGA is part of a noradrenergic/adrenergic gene panel that marks noradrenergic tumor clusters and postnatal chromaffin cells in normal adrenal gland.

Alterations observed in the corpus

• CHGA is part of the noradrenergic/adrenergic panel alongside PHOX2B, PHOX2A, TH, DBH, CHGB, PNMT, and ISL1; these genes mark the NOR (noradrenergic) tumor clusters and postnatal chromaffin cells in normal adrenal gland identified by single-nuclei RNA-seq of 11 neuroblastoma tumors PMID:34493726.
• Neuroendocrine expression marker defining SCLC transcriptional subtypes; distinguishes ASCL1-high neuroendocrine subtype from NOTCH-activated non-neuroendocrine SCLC PMID:26168399
• CHGA (chromogranin A) shows highest expression in the Wnt-altered PCC/PGL subtype (p<0.002), consistent with its role as a clinical neuroendocrine tumor marker; expression-based subtype classification in 173-patient TCGA PCC/PGL cohort PMID:28162975

Cancer types (linked)

• Neuroblastoma (NBL) — CHGA marks the noradrenergic/adrenergic low-risk tumor clusters (nC5/nC7/nC8/nC9) that are enriched in low-risk disease and associated with favorable outcome; expression is characteristic of adrenergic/chromaffin differentiation PMID:34493726.

Co-occurrence and mutual exclusivity

• Co-expressed with CHGB, PHOX2B, TH, DBH, and NTRK1 in the noradrenergic low-risk clusters; mutually exclusive with the NTRK2/ALK/MYCN-high undifferentiated nC3 high-risk cluster PMID:34493726.

Therapeutic relevance

• CHGA-positive noradrenergic tumor cells characterize low-risk neuroblastoma; their expression profile is associated with favorable prognosis through NTRK1 expression and adrenergic differentiation PMID:34493726.

Open questions

• Whether CHGA serum levels (a clinical biomarker for neuroendocrine tumors) correlate with the transcriptomic noradrenergic cluster identity in neuroblastoma is not addressed in the corpus.

Sources

• PMID:34493726

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