CDCP1 Expression Is a Potential Biomarker of Poor Prognosis in Resected Stage I Non-Small-Cell Lung Cancer

Abstract

Background: Although early-stage lung cancer has increased owing to the introduction of screening programs, high recurrence rate remains a critical concern. We aimed to explore biomarkers related to the prognosis of surgically resected non-small-cell lung cancer (NSCLC). Methods: In this retrospective study, we collected medical records of patients with NSCLC and matched tissue microarray blocks from surgical specimens. Semiquantitative immunohistochemistry was performed for measuring the expression level of fibroblast activation protein-alpha (FAP-α), Jagged-1 (JAG1), and CUB-domain-containing protein 1 (CDCP1). Results: A total of 453 patients who underwent complete resection between January 2011 and February 2012 were enrolled; 55.2% patients had stage I NSCLC, and 31.1% presented squamous cell carcinoma. Disease stage was a significant risk factor for recurrence and death, and age ≥ 65 years and male sex were associated with poor overall survival. FAP-a and JaG1 were not related to survivals, while CDCP1-expressing patients exhibited poor disease-free and overall survival. Moreover, CDCP1 expression in stage I NSCLC was significantly associated with recurrence. Conclusions: Old age, male sex, and high pathological stage were poor prognostic factors in patients with NSCLC who underwent surgical resection. Furthermore, CDCP1 expression could serve as a biomarker for poor prognosis in stage I NSCLC.

Mechanistic insights into CDCP1 clustering on non-small-cell lung cancer membranes revealed by super-resolution fluorescent imaging

“…CDCP1, a single-channel transmembrane protein, 4 is overexpressed in NSCLC and is significantly associated with poor prognosis in patients. 5 , 6 , 7 , 8 In malignant tumor cells, CDCP1 can be activated by Src kinase, which promotes the proliferation, invasion, and metastasis of tumor cells through classic signaling pathways such as MAPK (Ras/ERK) and PI3K/AKT. 9 , 10 , 11 , 12 , 13 Besides, numerous studies have demonstrated that antibodies targeting CDCP1, including MAB41-2, MAB10-D7, and C20Fc, can inhibit tumor growth and metastasis in various animal models and improve the efficacy of chemotherapy drugs.…”

“…Previous research studies on CDCP1 have been carried out mainly by Western blot, confocal microscopy, immunohistochemistry, and other methods to reflect the overall level. 6 , 18 However, the differences of its spatial distribution between cancer cells and normal cells and the relationship between its distribution and function are still unclear. In addition, there are few studies on super-resolution imaging of tissue sections, so the distribution of CDCP1 molecules in tissues has not been fully characterized.…”

Development of FAP-Targeted Chimeric Antigen Receptor NK-92 Cells for Non-Small Cell Lung Cancer

“…Highly expressed FAP-α in NSCLC has been shown in clinical studies to predict NSCLC patients' low survival [6]. Upregulated expression of FAP-α is likely to be correlated with inflammation and suppression of lymphocytedependent immune responses, leading to tumor progression [6,7]. Therefore, targeting FAP might be a potential therapeutic regimen for NSCLC.…”

Overexpression of CDCP1 is Associated with Poor Prognosis and Enhanced Immune Checkpoints Expressions in Breast Cancer

“…Given CDCP1 is highly expressed in RAS-driven cancers, targeting a proteolytic neoepitope on CDCP1 is a pan-cancer approach to control RAS-driven cancers [ 8 ]. In addition, CDCP1 is a prognostic biomarker in early non-small-cell lung cancer, and its high expression predicts a poor prognosis [ 9 ]. Although several studies have preliminarily investigated the oncogenic role of CDCP1 in BrCa [ 10 , 11 ], systematic analysis based on transcriptomics and its prognostic value in BrCa has not been defined yet.…”