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Expression Analysis of Early Metastatic Seeding of Colorectal Cancer

  • Translational Research
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

ABstract

Background

Distant metastasis is the leading cause of death in patients with colorectal cancer (CRC). Tumor dissemination for metastasis formation occurs in advanced cancers and also during early stages of tumorigenesis. Here, we investigated the genes involved in early metastatic seeding of CRC using gene expression analysis.

Patients and Methods

We performed a cDNA microarray using specimens resected from stages I–II CRC with and without metachronous metastatic recurrence. For the candidate genes, we immunohistochemically validated protein expression using a tissue microarray of stages I–III CRC.

Results

The expression of TROP2, VWCE, and BMP7 was upregulated in the recurrence group rather than in the non-recurrence group. Protein expression analysis revealed significant association of these genes with distant metastatic recurrence. The specimens with high expression of BMP7 showed worse recurrence-free survival (RFS; p = 0.02). Those with high expression of TROP2 and VWCE showed worse overall survival (OS) and RFS (TROP2: p = 0.01 and p = 0.03; VWCE: p < 0.05 and p < 0.001, respectively). In the multivariate analysis, high expression of VWCE and BMP7 was an independent predictor of recurrence [VWCE: hazard ratio (HR) 3.41, p < 0.001; BMP7: HR 2.93, p = 0.005]. In contrast, TROP2 was an independent prognostic factor for OS (HR 4.58, p = 0.03).

Conclusions

Gene expression analysis revealed that TROP2, VWCE, and BMP7 were involved in early metastatic seeding. The high expression of these genes may warrant careful surveillance or adjuvant therapy, even in stages I–II CRC cases.

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Acknowledgments

We would like to thank N Kobayashi, M. Horigome, A. Nange, and A. Okumura for their technical assistance, and all staff members at the Hokkaido University Hospital. The results shown here are based in part on data generated by the TCGA Research Network: https://www.cancer.gov/tcga.

Funding

This study was supported by JSPS KAKENHI Grant No. JP20K17670.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Akifumi Sawada MD, Masafumi Ohira MD, PhD, Hiroki Matsui MD, PhD, Nobuki Ichikawa MD, PhD, Tadashi Yoshida MD, PhD, Moto Fukai MD, PhD, Shigenori Homma MD, PhD & Akinobu Taketomi MD, PhD

  2. Center for Development of Advanced Diagnostics, Hokkaido University Hospital, Sapporo, Japan

    Kanako C. Hatanaka MD, PhD & Yutaka Hatanaka PhD

  3. Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan

    Yoshihiro Matsuno MD, PhD

  4. Research Division of Genome Companion Diagnostics, Hokkaido University Hospital, Sapporo, Japan

    Yutaka Hatanaka PhD

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  1. Akifumi Sawada MD
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Correspondence to Akinobu Taketomi MD, PhD.

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Sawada, A., Ohira, M., Hatanaka, K.C. et al. Expression Analysis of Early Metastatic Seeding of Colorectal Cancer. Ann Surg Oncol 31, 2101–2113 (2024). https://doi.org/10.1245/s10434-023-14714-7

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