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. 2025 Jan 3:12:1510264.
doi: 10.3389/fcell.2024.1510264. eCollection 2024.

Establishment and characterization of a sigmoid colon cancer organoid with spinal metastasis

Jingyao Chen #  1   2 , Shumin Cheng #  3 , Liang Gu #  1   2 , Zhangsen Huang  1   2 , Changhua Zhang  1   2 , Chunhui Sun  1   2   3 , Songyao Chen  1   2
Affiliations

Establishment and characterization of a sigmoid colon cancer organoid with spinal metastasis

Jingyao Chen et al. Front Cell Dev Biol. .

Abstract

Background: Sigmoid colon cancer with spinal metastases is rare in distant metastasis. In addition, the prognosis of colon cancer patients with spinal metastases is extremely poor. In order to find effective therapeutic agents, we need to know the biological characteristics of such patients from related models.

Methods: We collected sigmoid colon cancer tissue from a young female subject who was diagnosed with sigmoid colon cancer with multiple spinal metastases. We successfully established a sigmoid colon cancer organoid using this tissue and investigated drug screening in the patient. HE staining, immunohistochemistry, and DNA sequencing were utilized to compare the biological characteristics between the original tumor and the organoid. Furthermore, we investigated the drug screening of the sigmoid colon cancer organoid in vitro.

Results: A colon cancer organoid from sigmoid colon cancer with spinal metastases was successfully established. The organoid culture maintained the morphological features, histological features, and genomic landscape of the corresponding sigmoid colon cancer cells. Moreover, we performed drug screening tests to evaluate the effects of chemotherapeutic drugs and targeted drugs.

Conclusion: The sigmoid colon cancer organoid with spinal metastases was a favorable preclinical model to explore the clinicopathologic characteristics of colon cancer patients with spinal metastases.

Keywords: drug screening; genomic features; organoid culture; sigmoid colon cancer; spinal metastases.

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Conflict of interest statement

The 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
Treatment timeline and clinical characteristics of a case of primary advanced sigmoid colon cancer with bone metastasis. (A) Treatment timeline B-C. Abdominal computed tomography showing sigmoid colon carcinoma before (B) and after treatment (C) (white arrow). (D) PET-CT showing the multiple spinal metastases. (E) Enteroscopic image of stenosis caused by sigmoid colon carcinoma (red dotted circle).
FIGURE 2
FIGURE 2
Morphology of the sigmoid colon carcinoma organoid. (A) Time course of the sigmoid colon carcinoma organoid culture (scale bar, 50 μm). (B) Multiple lumen structure of the sigmoid colon carcinoma organoid (scale bar, 50 μm).
FIGURE 3
FIGURE 3
Histopathology and characterization of sigmoid colon carcinoma tissue (left column) and the organoid (right column). Scale bar, 50 μm.
FIGURE 4
FIGURE 4
Mutational signature of the sigmoid colon carcinoma tissue, organoid, and blood sample. (A) De novo signature SBS96A was identified in three samples and highly correlated with combinations of existing COSMIC signatures. (B) ID feature ID83A was identified in three samples and was highly correlated with combinations of existing COSMIC features. (C) A new de novo DBS feature, called feature DBS17, was found that was not mapped to any COSMIC DBS feature.
FIGURE 5
FIGURE 5
Somatic variant feature analysis. (A) Variant classification analysis. (B) Variant type analysis. (C) Class of point mutation analysis. (D) Number of mutations per sample analysis (left to right: blood, tissue, and organoid). (E) Variant classification summary. (F) Top 10 mutated genes.
FIGURE 6
FIGURE 6
Germline mutation feature analysis. (A) Variant classification analysis. (B) Variant type analysis. (C) Class of point mutation analysis. (D) Number of mutations per sample analysis (left to right: blood, tissue, and organoid). (E) Variant classification summary. (F) Top 10 mutated genes.
FIGURE 7
FIGURE 7
Somatic copy number variation analysis. (A) Heatmaps showing copy number amplifications (red) and deletions (blue) of standardized data for WES. (B) GISTIC2 figure showing significant local amplifications, including 8p11.21 and 16q11.2. (C) GISTIC2 map showing significant local deletions, including 1q21.3 and 2q21.1.
FIGURE 8
FIGURE 8
Enrichment pathway analysis utilizing the Metascape database.
FIGURE 9
FIGURE 9
Curves of the organoid treated with chemotherapeutic drugs, targeted medicines (A), and monoclonal antibodies (B). Dose–response curves of colon cancer cell lines to zoledronic acid (C).
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