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Upregulation of CALD1 predicted a poor prognosis for platinum-treated ovarian cancer and revealed it as a potential therapeutic resistance target.

作者信息

Li Wei, Huang Limei, Qi Nana, Zhang Qinle, Qin Zailong

机构信息

Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital, Children's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530002, China.

出版信息

BMC Genomics. 2024 Feb 16;25(1):183. doi: 10.1186/s12864-024-10056-0.

DOI:10.1186/s12864-024-10056-0
PMID:38365611
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10870461/
Abstract

BACKGROUND: Ovarian cancer (OC) has the worst prognosis among gynecological malignancies, most of which are found to be in advanced stage. Cell reduction surgery based on platinum-based chemotherapy is the current standard of treatment for OC, but patients are prone to relapse and develop drug resistance. The objective of this study was to identify a specific molecular target responsible for platinum chemotherapy resistance in OC. RESULTS: We screened the protein-coding gene Caldesmon (CALD1), expressed in cisplatin-resistant OC cells in vitro. The prognostic value of CALD1 was evaluated using survival curve analysis in OC patients treated with platinum therapy. The diagnostic value of CALD1 was verified by drawing a Receiver Operating Characteristic (ROC) curve using clinical samples from OC patients. This study analyzed data from various databases including Gene Expression Omnibus (GEO), Human Protein Atlas (HPA), The Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA), GEPIA 2, UALCAN, Kaplan-Meier (KM) plotter, LinkedOmics database, and String. Different expression genes (DEGs) between cisplatin-sensitive and cisplatin-resistant cells were acquired respectively from 5 different datasets of GEO. CALD1 was selected as a common gene from 5 groups DEGs. Online data analysis of HPA and CCLE showed that CALD1 was highly expressed in both normal ovarian tissue and OC. In TCGA database, high expression of CALD1 was associated with disease stage and venous invasion in OC. Patients with high CALD1 expression levels had a worse prognosis under platinum drug intervention, according to Kaplan-Meier (KM) plotter analysis. Analysis of clinical sample data from GEO showed that CALD1 had superior diagnostic value in distinguishing patients with platinum "resistant" and platinum "sensitive" (AUC = 0.816), as well as patients with worse progression-free survival (AUC = 0.741), and those with primary and omental metastases (AUC = 0.811) in ovarian tumor. At last, CYR61 was identified as a potential predictive molecule that may play an important role alongside CALD1 in the development of platinum resistance in OC. CONCLUSIONS: CALD1, as a member of cytoskeletal protein, was associated with poor prognosis of platinum resistance in OC, and could be used as a target protein for mechanism study of platinum resistance in OC.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/a14a494e3f52/12864_2024_10056_Fig16_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/d73882b478d6/12864_2024_10056_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/f170967b0cee/12864_2024_10056_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/b30a045eb41d/12864_2024_10056_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/4420a812fc82/12864_2024_10056_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/598307781978/12864_2024_10056_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/191f0f0958b6/12864_2024_10056_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/4f0ce85c9c07/12864_2024_10056_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/1cd9a5bd42aa/12864_2024_10056_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/8f8ff3888865/12864_2024_10056_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/b07c33d88a7c/12864_2024_10056_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/12181076cf20/12864_2024_10056_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/78ff3e37f83e/12864_2024_10056_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/03132e177f62/12864_2024_10056_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/6fa22dabf72a/12864_2024_10056_Fig14_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/358db7e0edfa/12864_2024_10056_Fig15_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/a14a494e3f52/12864_2024_10056_Fig16_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/d73882b478d6/12864_2024_10056_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/f170967b0cee/12864_2024_10056_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/b30a045eb41d/12864_2024_10056_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/4420a812fc82/12864_2024_10056_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/598307781978/12864_2024_10056_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/191f0f0958b6/12864_2024_10056_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/4f0ce85c9c07/12864_2024_10056_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/1cd9a5bd42aa/12864_2024_10056_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/8f8ff3888865/12864_2024_10056_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/b07c33d88a7c/12864_2024_10056_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/12181076cf20/12864_2024_10056_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/78ff3e37f83e/12864_2024_10056_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/03132e177f62/12864_2024_10056_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/6fa22dabf72a/12864_2024_10056_Fig14_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/358db7e0edfa/12864_2024_10056_Fig15_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ee/10870461/a14a494e3f52/12864_2024_10056_Fig16_HTML.jpg

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引用本文的文献

[1]
inhibits invasion of human ovarian cancer cells by affecting cytoskeletal structure and the number of focal adhesion.

Transl Cancer Res. 2025-2-28

本文引用的文献

[1]
Identification of RECK as a protective prognostic indicator and a tumor suppressor through regulation of the ERK/MAPK signaling pathway in gastric cancer.

J Transl Med. 2023-10-30

[2]
Platinum-based chemotherapy for early triple-negative breast cancer.

Cochrane Database Syst Rev. 2023-9-8

[3]
KEGG for taxonomy-based analysis of pathways and genomes.

Nucleic Acids Res. 2023-1-6

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Molecular mechanisms of platinum‑based chemotherapy resistance in ovarian cancer (Review).

Oncol Rep. 2022-4

[5]
CALD1 is a prognostic biomarker and correlated with immune infiltrates in gastric cancers.

Heliyon. 2021-6-9

[6]
The cancer-associated fibroblasts related gene CALD1 is a prognostic biomarker and correlated with immune infiltration in bladder cancer.

Cancer Cell Int. 2021-5-29

[7]
Weighted Gene Co-expression Network Analysis Identifies CALD1 as a Biomarker Related to M2 Macrophages Infiltration in Stage III and IV Mismatch Repair-Proficient Colorectal Carcinoma.

Front Mol Biosci. 2021-4-29

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Revisiting antibody-drug conjugates and their predictive biomarkers in platinum-resistant ovarian cancer.

Semin Cancer Biol. 2021-12

[9]
Recent advances in drug delivery systems for targeting cancer stem cells.

Acta Pharm Sin B. 2021-1

[10]
The Roles of CCN1/CYR61 in Pulmonary Diseases.

Int J Mol Sci. 2020-10-22

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