Posted in Asia-Pacific, Research

FBXW7 and Its Downstream NOTCH Pathway Could be Potential Indicators of Organ-Free Metastasis in Colorectal Cancer

 September 12, 2022


doi: 10.3389/fonc.2021.783564.


eCollection 2021.

Dongzheng Li 
1
, Shiye Jiang 
1
, Xin Zhou 
1
, Chengshuai Si 
1
, Peng Shao 
1
, Qian Jiang 
1
, Liuqing Zhu 
2
, Lu Shen 
2
, Qi Meng 
2
, Jiani C Yin 
2
, Yang Shao 
2
 
3
, Yueming Sun 
4
, Liu Yang 
1

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Dongzheng Li et al.


Front Oncol.


.

Free PMC article

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths globally. Metastasis is associated with a poor prognosis, yet the underlying molecular mechanism(s) remained largely unknown. In this study, a total of 85 CRC patients were included and the primary tumor lesions were evaluated by next-generation sequencing using a targeted panel for genetic aberrations. Patients were sub-divided according to their metastasis pattern into the non-organ metastases (Non-OM) and organ metastases (OM) groups. By comparing the genetic differences between the two groups, we found that mutations in FBXW7 and alterations in its downstream NOTCH signaling pathway were more common in the Non-OM group. Moreover, correlation analysis suggested that FBXW7 mutations were independent of other somatic alterations. The negative associations of alterations in FBXW7 and its downstream NOTCH signaling pathway with CRC organ metastasis were validated in a cohort of 230 patients in the TCGA CRC dataset. Thus, we speculated that the genomic alterations of FBXW7/NOTCH axis might be an independent negative indicator of CRC organ metastases.


Keywords:

FBXW7; NGS; NOTCH; colorectal cancer; organ metastasis.

Conflict of interest statement

LZ, LS, QM, JY, and YS are the employees of Nanjing Geneseeq Technology Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures


Figure 1



Figure 1

The clinical information and mutational spectrum of the colorectal patients in this study. Comparison of the mutational profile between the Non-OM and OM subgroups. The top 21 genes of the NGS cohort and P-values according to the Fisher’s exact were shown.


Figure 2



Figure 2

The somatic mutational type proportion of this cohort.


Figure 3



Figure 3

The somatic interactions of the study. Significant exclusive or co-occurrent variants were analyzed with Fisher’s exact test.

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References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin (2018) 68:394–424. doi: 10.3322/caac.21492

      –

      DOI

      –

      PubMed

    1. Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell (2011) 144:646–74. doi: 10.1016/j.cell.2011.02.013

      –

      DOI

      –

      PubMed

    1. Valastyan S, Weinberg RA. Tumor Metastasis: Molecular Insights and Evolving Paradigms. Cell (2011) 147:275–92. doi: 10.1016/j.cell.2011.09.024

      –

      DOI

      –

      PMC

      –

      PubMed

    1. Croner RS, Fortsch T, Bruckl WM, Rodel F, Rodel C, Papadopoulos T, et al. . Molecular Signature for Lymphatic Metastasis in Colorectal Carcinomas. Ann Surg (2008) 247:803–10. doi: 10.1097/SLA.0b013e31816bcd49

      –

      DOI

      –

      PubMed

    1. Pretzsch E, Bosch F, Neumann J, Ganschow P, Bazhin A, Guba M, et al. . Mechanisms of Metastasis in Colorectal Cancer and Metastatic Organotropism: Hematogenous Versus Peritoneal Spread. J Oncol (2019) 2019:7407190. doi: 10.1155/2019/7407190

      –

      DOI

      –

      PMC

      –

      PubMed

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