Proteomic profiling of antibody-inducing immunogens in tumor tissue identifies PSMA1, LAP3, ANXA3, and maspin as colon cancer markers

Abstract

We hypothesized that cancer tissue immunogens – antigens capable of inducing specific antibody production in patients – are promising targets for development of precision diagnostics and humoral immunotherapies. We developed an innovative immuno-proteomic strategy and identified new immunogenic markers of colon cancer. Proteins from cancers and matched normal tissues were separated by 2D gel electrophoresis and blotted with serum antibodies from the same patients. Antibody-reactive proteins were sequenced by mass spectrometry and validated by Western blotting and immunohistochemistry. 170 serum antibody-reactive proteins were identified only in cancerous but not matched normal. Among these, proteasome subunit alpha type 1 (PSA1), leucine aminopeptidase 3 (LAP3), annexin A3 (ANXA3), and maspin (serpin B5) were reproducibly found in tissues from three patients. Differential expression patterns were confirmed in samples from eight patients with various stages of colon adenocarcinoma and liver metastases. These tumor-resident proteins and/or their associated serum antibodies may be promising markers for colon cancer screening and early diagnosis. Furthermore, tumor tissue-specific antibodies could potentially be exploited as immunotherapeutic targets against cancer. More generally, proteomic profiling of antibody-inducing cancer-associated immunogens represents a powerful generic method for uncovering the tumor antigen-ome, i.e., the totality of immunogenic tumor-associated proteins.

Detecting Prognosis Risk Biomarkers for Colon Cancer Through Multi-Omics-Based Prognostic Analysis and Target Regulation Simulation Modeling

“…Furthermore, 45 prognosis-related features were obtained through the analysis of PPI networks and mapped into multiple cancer-related pathways. Among them, some prognosis-related features were directly related with the occurrence, development or prognosis of cancer, such as PSMA1 (degree = 54) was identified as colon cancer markers by proteomic profiling (Yang et al, 2018), FGFR3 (degree = 37) was related with multi-regional colon cancer through inter-and intra-tumor profiling (Kogita et al, 2015), ALPi is selectively induced by HDACi in colon cancer cells in a KLF5 (degree = 13) dependent manner (Shin et al, 2014), GLS2 (degree = 10) was validated as differential expression gene in colon cancer cells (Alix-Panabieres et al, 2017) and LEP (degree = 10) was examined to be associated with the development of colorectal cancer (Rezaei-Tavirani et al, 2013). Furthermore, several pathways were provided to be colon cancer-related pathways, such as wnt pathway, PI3K-AKT signaling pathway and cell cycle signaling pathway were reported as common oncogenic signaling pathways (Sanchez-Vega et al, 2018), which could be regulated by PSMA1 (degree = 54), MRAS (degree = 10), and LEP (degree = 10), respectively.…”

Cancer‐associated fibroblasts contribute to cisplatin resistance by modulating ANXA3 in lung cancer cells

“…Recent studies show that ANXA3 plays an important role in tumor growth and progression. Clinical evidence indicates that ANXA3 could be a potential biomarker of several types of cancers, such as bladder cancer, colon cancer and gastric cancer . It can also serve as an important marker for the invasion, the metastasis and the prognosis of breast cancer…”

STAT1 as a potential prognosis marker for poor outcomes of early stage colorectal cancer with microsatellite instability

“…To better characterize and stratify cancer at the molecular level, we have embarked on an intense effort to identify molecular biomarkers of colorectal and other cancers with the goal of developing more efficient risk stratification for cancer diagnosis and treatment [11][12][13][14]. By deep proteome profiling of CRC by mass spectrometry, we observed that the protein STAT1 is upregulated in a subset of CRCs.…”