Volume 47, Issue 5 pp. 609-618
ORIGINAL ARTICLE

Correlation between CA12 and TFF3 and their prediction value of neoadjuvant chemotherapy response in breast cancer

Mengjia Shen MD, PhD

Mengjia Shen MD, PhD

Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Libo Yang MD, PhD

Libo Yang MD, PhD

Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Ting Lei MD, PhD

Ting Lei MD, PhD

Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China

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Peichuan Zhang MS

Peichuan Zhang MS

Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

Key Lab of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Lin Xiao BS

Lin Xiao BS

Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Shiyu Cao MS

Shiyu Cao MS

Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Fei Chen BS

Fei Chen BS

Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Li Li MS

Li Li MS

Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Feng Ye PhD

Feng Ye PhD

Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

Key Lab of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Hong Bu MD, PhD

Corresponding Author

Hong Bu MD, PhD

Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

Key Lab of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, China

Correspondence

Hong Bu, Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China, Department of Pathology, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan, China, Key Lab of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Email: [email protected]

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First published: 28 February 2022
Citations: 3

Funding information

The authors did not receive support from any organization for the submitted work.

Abstract

What is known and Objective

Compared with other molecular subtypes, hormone receptor-positive breast cancer often shows worse neoadjuvant chemotherapy efficacy. This study aims to explore the relationship between the oestrogen receptor (ER)-related genes carbonic anhydrase 12 (CA12) and trefoil factor 3 (TFF3) and their predictive value of neoadjuvant chemotherapy for breast cancer.

Methods

We investigated the relationships between CA12, TFF3 and ER status and their predictive value of anthracycline-taxane neoadjuvant chemotherapy in 115 female breast cancer patients via real-time polymerase chain reaction (RT-PCR) and 4 GEO datasets: GSE41998, GSE25065, GSE20194 and GSE20271. Then, the effects of CA12 and TFF3 on the chemotherapy drugs doxorubicin and docetaxel were verified in vitro in the breast cancer cell lines MCF-7 and BT474.

Results and Discussion

The GEO datasets and RT-PCR results showed that the relative expression of both CA12 and TFF3 was higher in oestrogen receptor-positive samples compared with the other samples (< 0.05). CA12 was significantly correlated with TFF3 (< 0.05). In MCF-7 cells, inhibition of TFF3 induced downregulation of CA12 and ESR1 (< 0.05) at both the mRNA and the protein levels, while inhibition of CA12 also downregulated TFF3 and ESR1 (< 0.05). In BT474 cells, inhibition of TFF3 downregulated CA12 and ESR1 (< 0.05) at both the mRNA and the protein levels, while inhibition of CA12 led to slight upregulation of TFF3 and ESR1 (> 0.05). Moreover, GEO datasets and RT-PCR results showed that CA12 and TFF3 were more highly expressed in nonpathological complete response (non-pCR) samples than in pCR samples (< 0.05). Cell viability assays of MCF-7 and BT474 cells showed that inhibiting CA12 and TFF3 could enhance sensitivity to doxorubicin and docetaxel (< 0.05).

What is new and Conclusion

CA12 and TFF3 were correlated with each other, and their high expression might explain the worse efficacy of neoadjuvant chemotherapy in oestrogen receptor-positive breast cancer patients.

CONFLICTS OF INTEREST

No conflicts of interest have been declared.

DATA AVAILABILITY STATEMENT

The datasets analysed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).

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