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CTHRC1与（V600E）突变相关，并与结肠癌、甲状腺癌和黑色素瘤的预后、免疫细胞浸润及耐药性相关。

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

作者信息

Zhang Rumeng, Wang Zhihao, Wang Huan, Li Lin, Dong Lin, Ding Lin, Li Qiushuang, Zhu Linyan, Zhang Tiantian, Zhu Yong, Ding Keshuo

机构信息

Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China.

Department of Pathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China.

出版信息

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

DOI:10.17305/bb.2024.10397
PMID:39052013
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11647256/
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.

摘要

结肠癌、甲状腺癌和黑色素瘤是全球范围内严重威胁人类健康的常见恶性肿瘤。B-Raf原癌基因丝氨酸/苏氨酸激酶（BRAF）（V600E）突变是这些癌症类型中的一种重要驱动基因突变。在本研究中，我们发现含胶原三螺旋重复序列1（CTHRC1）的表达与结肠癌、甲状腺癌和黑色素瘤中的BRAF（V600E）突变相关。基于数据库分析和临床组织研究，CTHRC1被证实与结肠癌和甲状腺癌患者的预后不良及较差的临床病理特征相关，但在黑色素瘤患者中并非如此。几种信号通路、免疫细胞浸润和免疫治疗标志物与CTHRC1表达相关。此外，高水平的CTHRC1与针对BRAF（V600E）突变的抗肿瘤药物（维莫非尼、PLX-4720、达拉非尼和SB-590885）敏感性降低相关。本研究提供了CTHRC1与BRAF（V600E）突变之间显著相关性的证据，表明其在人类结肠癌、甲状腺癌和黑色素瘤中作为诊断和预后生物标志物的潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/1e84790c4791/bb-2024-10397f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/0432a6fca135/bb-2024-10397f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/4f88f84395af/bb-2024-10397f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/b059cadcd3d5/bb-2024-10397f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/141e7c8f928c/bb-2024-10397f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/6250a7652a7e/bb-2024-10397f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/9e3f3ae67063/bb-2024-10397f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/3de8219ab711/bb-2024-10397f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/1e84790c4791/bb-2024-10397f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/0432a6fca135/bb-2024-10397f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/4f88f84395af/bb-2024-10397f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/b059cadcd3d5/bb-2024-10397f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/141e7c8f928c/bb-2024-10397f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/6250a7652a7e/bb-2024-10397f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/9e3f3ae67063/bb-2024-10397f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/3de8219ab711/bb-2024-10397f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2347/11647256/1e84790c4791/bb-2024-10397f8.jpg

相似文献

[1]
CTHRC1 is associated with (V600E) mutation and correlates with prognosis, immune cell infiltration, and drug resistance in colon cancer, thyroid cancer, and melanoma.

Biomol Biomed. 2024-12-11

[2]
Unusually long-term responses to vemurafenib in BRAF V600E mutated colon and thyroid cancers followed by the development of rare RAS activating mutations.

Cancer Biol Ther. 2018-7-23

[3]
Long-term vemurafenib treatment drives inhibitor resistance through a spontaneous KRAS G12D mutation in a BRAF V600E papillary thyroid carcinoma model.

Oncotarget. 2016-5-24

[4]
Dabrafenib therapy for advanced melanoma.

Ann Pharmacother. 2014-4

[5]
B-Raf Inhibition in the Clinic: Present and Future.

Annu Rev Med. 2016

[6]
Autophagy sustains mitochondrial respiration and determines resistance to BRAF inhibition in thyroid carcinoma cells.

Autophagy. 2024-6

[7]
Dabrafenib and its potential for the treatment of metastatic melanoma.

Drug Des Devel Ther. 2012

[8]
Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial.

Lancet Oncol. 2016-9

[9]
Preexisting MEK1 exon 3 mutations in V600E/KBRAF melanomas do not confer resistance to BRAF inhibitors.

Cancer Discov. 2012-4-1

[10]
Mechanisms of resistance to RAF inhibition in melanomas harboring a BRAF mutation.

Am Soc Clin Oncol Educ Book. 2013

引用本文的文献

[1]
A Narrative Review of the Role of Immunotherapy in Metastatic Carcinoma of the Colon Harboring a BRAF Mutation.

In Vivo. 2025

本文引用的文献

[1]
Integrated analysis of novel macrophage related signature in anaplastic thyroid cancer.

Endocrine. 2022-12

[2]
Application Potential of as a Diagnostic and Prognostic Indicator for Colon Adenocarcinoma.

Front Mol Biosci. 2022-3-1

[3]
CTHRC1 facilitates bladder cancer cell proliferation and invasion through regulating the PI3K/Akt signaling pathway.

Arch Med Sci. 2019-6-6

[4]
Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma.

N Engl J Med. 2022-1-6

[5]
MicroRNA Regulates the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Targeting CTHRC1.

Stem Cells Int. 2021-12-14

[6]
Colon cancer cells acquire immune regulatory molecules from tumor-infiltrating lymphocytes by trogocytosis.

Proc Natl Acad Sci U S A. 2021-11-30

[7]
ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation.

J Biomed Sci. 2021-11-13

[8]
RNF43 inhibits WNT5A-driven signaling and suppresses melanoma invasion and resistance to the targeted therapy.

Elife. 2021-10-27

[9]
NUDT21 Promotes Tumor Growth and Metastasis Through Modulating SGPP2 in Human Gastric Cancer.

Front Oncol. 2021-9-30

[10]
Alterations Induce Acquired Dabrafenib Resistance in Association with Anaplastic Transformation in a Papillary Thyroid Cancer Patient.

Cancers (Basel). 2021-9-30

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