Phenotypic Heterogeneity Analysis of APC-Mutant Colon Cancer by Proteomics and Phosphoproteomics Identifies RAI14 as a Key Prognostic Determinant in East Asians and Westerners

Zhang, Rou; Hu, Meng; Chen, Hai‐Ning; Wang, Xiuxuan; Xia, Zhili; Liu, Yu; Wang, Rui; Xia, Xuyang; Yang, Sen; Du, Dan; Meng, Wenbo; Qi, Shiqian; Li, Yuan; Xu, Heng; Zhou, Zong-Guang; Dai, Lunzhi

doi:10.1016/j.mcpro.2023.100532

Cited by 10 publications

(4 citation statements)

References 61 publications

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“…Previous reports have shown that AKR1B10 is downregulated in CRCs [19] and acts as a tumor suppressor [20, 21]. In contrast, the 6 downregulated genes have been reported as oncogenes in various neoplastic diseases, including CRC [22‒27]. These results suggest that VSNL1 plays an important role in regulating the transcription of downstream tumor-associated genes, leading to promotion of cell proliferation in CRCs.…”

Section: Resultsmentioning

confidence: 92%

Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis

Aiba,

Hijiya,

Akagi

et al. 2023

Pathobiology

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Introduction: We have previously reported that overexpression of VSNL1 (Visinin-like protein 1) is frequently observed in advanced colorectal adenocarcinomas and correlates with poorer prognosis. In this study, we determined the levels of VSNL1 expression in the earlier stages of colorectal tumors including adenomas and adenocarcinomas, and attempted to clarify the functional significance of VSNL1 overexpression in colorectal carcinogenesis. Methods: Levels of VSNL expression in colorectal tumor tissues were analyzed using immunohistochemistry. The effects of VSNL1 downregulation and overexpression on cell proliferation, resistance to apoptosis and invasiveness were determined using two VSNL1-overexpressing colorectal cancer cell lines, CW-2 and HCT116 and VSNL1 inducibly expressing SNU-C5, respectively. Gene expression signatures in VSNL1-downregulated CW-2 and HCT116 were identified using transcriptome and gene set enrichment analyses. Results: VSNL1 expression was restricted to only a few crypt cells in the non-tumorous epithelium, whereas it became enhanced in adenomas and adenocarcinomas with the progression of tumorigenesis. Downregulation of VSNL1 in CW-2 and HCT116 cells suppressed their proliferation through induction of apoptosis. Conversely, overexpression of VSNL1 in SNU-C5 cells enhanced resistance to anoikis. Transcriptome and gene set enrichment analyses revealed that downregulation of VSNL1 altered the expression level of the apoptosis-related gene set in CW-2 and HCT116 cells. Conclusion: VSNL1 plays a role in both the development and progression of colorectal tumors by enhancing cell viability.

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Section: Resultsmentioning

confidence: 92%

Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis

Aiba,

Hijiya,

Akagi

et al. 2023

Pathobiology

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“…The CPTAC dataset was essential in this process, as it is the only one that contains survival data. This dataset has been frequently used for confirmation of previously identified prognostic biomarkers, usually through genomics or transcriptomics approaches [ 38 , 39 ]. In our study, we performed a large-scale analysis identifying all the proteins associated with prognosis according to CPTAC.…”

Section: Discussionmentioning

confidence: 99%

Integrated meta-analysis of colorectal cancer public proteomic datasets for biomarker discovery and validation

Robles,

Prakash,

Vizcaíno

et al. 2024

PLoS Comput Biol

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The cancer biomarker field has been an object of thorough investigation in the last decades. Despite this, colorectal cancer (CRC) heterogeneity makes it challenging to identify and validate effective prognostic biomarkers for patient classification according to outcome and treatment response. Although a massive amount of proteomics data has been deposited in public data repositories, this rich source of information is vastly underused. Here, we attempted to reuse public proteomics datasets with two main objectives: i) to generate hypotheses (detection of biomarkers) for their posterior/downstream validation, and (ii) to validate, using an orthogonal approach, a previously described biomarker panel. Twelve CRC public proteomics datasets (mostly from the PRIDE database) were re-analysed and integrated to create a landscape of protein expression. Samples from both solid and liquid biopsies were included in the reanalysis. Integrating this data with survival annotation data, we have validated in silico a six-gene signature for CRC classification at the protein level, and identified five new blood-detectable biomarkers (CD14, PPIA, MRC2, PRDX1, and TXNDC5) associated with CRC prognosis. The prognostic value of these blood-derived proteins was confirmed using additional public datasets, supporting their potential clinical value. As a conclusion, this proof-of-the-concept study demonstrates the value of re-using public proteomics datasets as the basis to create a useful resource for biomarker discovery and validation. The protein expression data has been made available in the public resource Expression Atlas.

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“…APC normally serves as a tumor suppressor by regulating the Wnt signaling pathway. Mutations in APC lead to uncontrolled activation of the Wnt pathway, resulting in excessive cell proliferation and the formation of benign polyps that can eventually progress to cancer. , Another common driver mutation is found in the Kirsten rat sarcoma viral oncogene homologue (KRAS) gene. Activating mutations in KRAS are often associated with resistance to antiepidermal growth factor receptor (EGFR) therapies.…”

Section: Molecular Profiling Of Colorectal Cancermentioning

confidence: 99%

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

Kiran,

Yashaswini,

Maheshwari

et al. 2024

ACS Pharmacol. Transl. Sci.

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Precision medicine is transforming colorectal cancer treatment through the integration of advanced technologies and biomarkers, enhancing personalized and effective disease management. Identification of key driver mutations and molecular profiling have deepened our comprehension of the genetic alterations in colorectal cancer, facilitating targeted therapy and immunotherapy selection. Biomarkers such as microsatellite instability (MSI) and DNA mismatch repair deficiency (dMMR) guide treatment decisions, opening avenues for immunotherapy. Emerging technologies such as liquid biopsies, artificial intelligence, and machine learning promise to revolutionize early detection, monitoring, and treatment selection in precision medicine. Despite these advancements, ethical and regulatory challenges, including equitable access and data privacy, emphasize the importance of responsible implementation. The dynamic nature of colorectal cancer, with its tumor heterogeneity and clonal evolution, underscores the necessity for adaptive and personalized treatment strategies. The future of precision medicine in colorectal cancer lies in its potential to enhance patient care, clinical outcomes, and our understanding of this intricate disease, marked by ongoing evolution in the field. The current reviews focus on providing in-depth knowledge on the various and diverse approaches utilized for precision medicine against colorectal cancer, at both molecular and biochemical levels.

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Phenotypic Heterogeneity Analysis of APC-Mutant Colon Cancer by Proteomics and Phosphoproteomics Identifies RAI14 as a Key Prognostic Determinant in East Asians and Westerners

Cited by 10 publications

References 61 publications

Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis

Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis

Integrated meta-analysis of colorectal cancer public proteomic datasets for biomarker discovery and validation

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

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