Revised Exon Structure of l-DOPA Decarboxylase (DDC) Reveals Novel Splice Variants Associated with Colorectal Cancer Progression

Abstract

Colorectal cancer (CRC) is a highly heterogenous malignancy with an increased mortality rate. Aberrant splicing is a typical characteristic of CRC, and several studies support the prognostic value of particular transcripts in this malignancy. l-DOPA decarboxylase (DDC) and its derivative neurotransmitters play a multifaceted role in physiological and pathological states. Our recent data support the existence of 6 DDC novel exons. In this study, we investigated the existence of additional DDC novel exons and transcripts, and their potential value as biomarkers in CRC. Next-generation sequencing (NGS) in 55 human cell lines coupled with Sanger sequencing uncovered 3 additional DDC novel exons and 20 splice variants, 7 of which likely encode new protein isoforms. Eight of these transcripts were detected in CRC. An in-house qPCR assay was developed and performed in TNM II and III CRC samples for the quantification of transcripts bearing novel exons. Extensive biostatistical analysis uncovered the prognostic value of specific DDC novel exons for patients’ disease-free and overall survival. The revised DDC exon structure, the putative protein isoforms with distinct functions, and the prognostic value of novel exons highlight the pivotal role of DDC in CRC progression, indicating its potential utility as a molecular biomarker in CRC.

Multi-omics profiles refine L-dopa decarboxylase (DDC) as a reliable biomarker for prognosis and immune microenvironment of clear cell renal cell carcinoma

“…However, in prostate cancer, the higher expression of DDC was associated with advanced stages, higher Gleason scores, biochemical recurrence, and short disease-free survival (DFS) ( 22 ). Also, the role of DDC has been investigated in the development of colorectal cancer ( 23 ), small cell lung cancer ( 24 ), and gastric cancer ( 25 ). However, the prognostic value and underlying mechanism caused by aberrant L-dopa decarboxylase expression have not been systematically elucidated in ccRCC.…”

Identification and immunological characterization of cuproptosis-related molecular clusters in Ulcerative Colitis

“…Salewski et al, 2022 reported that colonic in ammation is correlated with VIL1 protein expression, according to a study [36]. Artemaki et al, 2020 reported that positive correlation exists between DDC protein expression levels and unfavorable CRC prognoses [37]. DEGs and biological characteristic differences between the two molecular clusters.…”

Evaluation of the ability of fatty acid metabolism signature to predict response to neoadjuvant chemoradiotherapy and prognosis of patients with locally advanced rectal cancer

“…In addition, the expression level of RIOK3 increases with hypoxia, which is an important factor in preventing effective radiotherapy and immunotherapy of cancer ( 51 , 52 ). l -DOPA decarboxylase ( DDC ) has been proposed in recent research to serve apoptotic and antiproliferative functions with phosphatidylinositol 3-kinase (PI3K) ( 53 , 54 ). Moreover, high expression of DDC is closely associated with better prognosis in CRC ( 55 ).…”