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. 2024 Dec 11;25(1):42-61.
doi: 10.17305/bb.2024.10397.

CTHRC1 is associated with BRAF(V600E) mutation and correlates with prognosis, immune cell infiltration, and drug resistance in colon cancer, thyroid cancer, and melanoma

Rumeng Zhang  1 , Zhihao Wang  2 , Huan Wang  3 , Lin Li  2 , Lin Dong  2 , Lin Ding  2 , Qiushuang Li  4 , Linyan Zhu  2 , Tiantian Zhang  4 , Yong Zhu  4 , Keshuo Ding  5
Affiliations

CTHRC1 is associated with BRAF(V600E) mutation and correlates with prognosis, immune cell infiltration, and drug resistance in colon cancer, thyroid cancer, and melanoma

Rumeng Zhang et al. Biomol Biomed. .

Abstract

Colon cancer, thyroid cancer, and melanoma are common malignant tumors that seriously threaten human health globally. The B-Raf proto-oncogene, serine/threonine kinase (BRAF)(V600E) mutation is an important driver gene mutation in these cancer types. In this study, we identified that collagen triple helix repeat containing 1 (CTHRC1) expression was associated with the BRAF(V600E) mutation in colon cancer, thyroid cancer, and melanoma. Based on database analysis and clinical tissue studies, CTHRC1 was verified to correlate with poor prognosis and worse clinicopathological features in colon cancer and thyroid cancer patients, but not in patients with melanoma. Several signaling pathways, immune cell infiltration, and immunotherapy markers were associated with CTHRC1 expression. Additionally, a high level of CTHRC1 was correlated with decreased sensitivity to antitumor drugs (vemurafenib, PLX-4720, dabrafenib, and SB-590885) targeting the BRAF(V600E) mutation. This study provides evidence of a significant correlation between CTHRC1 and the BRAF(V600E) mutation, suggesting its potential utility as a diagnostic and prognostic biomarker in human colon cancer, thyroid cancer, and melanoma.

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Conflict of interest statement

Conflicts of interest: Authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Correlation analysis of BRAF(V600E) mutation with gene expression in colon cancer, thyroid cancer, and melanoma based on the TCGA database. (A) Volcano plots showed genes that are downregulated or upregulated in BRAF(V600E) mutant tissues compared with wild-type tissues of colon cancer, thyroid cancer, and melanoma, respectively (COAD, colon cancer, THCA, thyroid cancer, SKCM, melanoma); (B) Intersection analysis of the genes up expressed in BRAF(V600E) mutant colon cancer, thyroid cancer, and melanoma tissues, with 5 potential oncogenes identified for further study.
Figure 2.
Figure 2.
CTHRC1 was highly expressed in BRAF(V600E) mutant colon cancer, thyroid cancer, and melanoma tissues. (A) Correlation of CTHRC1 expression and BRAF(V600E) mutation in colon cancer, thyroid cancer, and melanoma tissues based on the TCGA database; (B) CTHRC1 mRNA expression in BRAF(V600E) mutant and wild-type colon cancer, thyroid cancer, and melanoma tissues based on the TCGA database; (C) CTHRC1 mRNA expression in BRAF(V600E) mutant and wild-type colon cancer, thyroid cancer, and melanoma clinical tissues collected from the Department of Pathology, First Affiliated Hospital of Anhui Medical University, as examined by qRT-PCR. *P < 0.05; ***P < 0.001. CTHRC1: Collagen triple helix repeat containing 1; qRT-PCR: Quantitative real-time PCR.
Figure 3.
Figure 3.
OS rate and ROC curve analyses of CTHRC1 in colon cancer, thyroid cancer, and melanoma based on the TCGA database. (A–C) Patient OS rates in the CTHRC1 high and low expression groups were analyzed using Kaplan–Meier analysis in colon cancer, thyroid cancer, and melanoma respectively; (D–F) The receiver operating characteristic (ROC) curves of CTHRC1 for the diagnosis of colon cancer, thyroid cancer, and melanoma respectively. CTHRC1: Collagen triple helix repeat containing 1; OS: Overall survival.
Figure 4.
Figure 4.
PPI and molecular signaling pathway enrichment analyses of CTHRC1 in colon cancer, thyroid cancer, and melanoma. (A) PPI network of CTHRC1 analyzed using the STRING tool; (B) Histogram showing the GO and KEGG pathway analyses of CTHRC1; (C) Top5 GSEA (gene set enrichment analysis) results for CTHRC1. CTHRC1: Collagen triple helix repeat containing 1; PPI: Protein–protein interaction; GO: Gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes.
Figure 5.
Figure 5.
Correlation analysis of CTHRC1 expression with immune cell infiltration and immunotherapy markers in colon cancer, thyroid cancer, and melanoma. (A) Correlation of CTHRC1 expression with 24 types of immune cells calculated using Cibersort; (B) Correlation of CTHRC1 expression with respective immune cells based on the TIMER database; (C) Heatmap of CTHRC1 associated immunotherapy markers CD274, PDCD1, CTLA4 and LAG3. **P < 0.01; ***P < 0.001. CTHRC1: Collagen triple helix repeat containing 1.
Figure 6.
Figure 6.
CTHRC1 and immune cell marker levels in colon cancer and thyroid cancer clinical tissues with/without BRAF(V600E) mutation. IHC showing CTHRC1, CD4, CD8, CD68, CD69, and Ki-67 protein levels in colon cancer and thyroid cancer clinical tissues with/without BRAF(V600E) mutation. Representative photographs are shown. BRAF(V600E), BRAF(V600E) mutation; BRAF WT, BRAF wild-type. CTHRC1: Collagen triple helix repeat containing 1; IHC: Immunohistochemistry.
Figure 7.
Figure 7.
Correlation analysis of CTHRC1 expression with anticancer drug sensitivity. The correlations of CTHRC1 expression with anticancer drug sensitivity (Vemurafenib, PLX-4720, Dabrafenib, SB-590885, PI-103, Hypothemycin, OSI-027, AFP464, Aminoflavone) were analyzed based on the CellMiner database. CTHRC1: Collagen triple helix repeat containing 1.
Figure S1.
Figure S1.
CTHRC1 and immune cell marker levels in melanoma tissues with/without BRAF(V600E) mutation. IHC to show CTHRC1, CD4, CD8, CD68, CD69, and Ki-67 protein levels in melanoma tissues with/without BRAF(V600E) mutation. Representative photographs were showed. BRAF(V600E), BRAF(V600E) mutation, BRAF WT, BRAF wild-type. CTHRC1: Collagen triple helix repeat containing 1; IHC: Immunohistochemistry.
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