Asghar K, Loya A, Rana IA, Bakar MA, Farooq A, Tahseen M, Ishaq M, Masood I, Rashid MU. Forkhead box P3 and indoleamine 2,3-dioxygenase co-expression in Pakistani triple negative breast cancer patients. World J Clin Oncol 2020; 11(12): 1018-1028 [PMID: 33437664 DOI: 10.5306/wjco.v11.i12.1018]
Corresponding Author of This Article
Kashif Asghar, DVM, PhD, Research Scientist, Department of Basic Science Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, 7A, Block R3, Johar Town, Lahore, Punjab 54000, Pakistan. drkashifasghar@gmail.com
Research Domain of This Article
Immunology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Dec 24, 2020; 11(12): 1018-1028 Published online Dec 24, 2020. doi: 10.5306/wjco.v11.i12.1018
Forkhead box P3 and indoleamine 2,3-dioxygenase co-expression in Pakistani triple negative breast cancer patients
Kashif Asghar, Asif Loya, Iftikhar Ali Rana, Muhammad Abu Bakar, Asim Farooq, Muhammad Tahseen, Muhammad Ishaq, Iqra Masood, Muhammad Usman Rashid
Kashif Asghar, Muhammad Usman Rashid, Department of Basic Science Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab 54000, Pakistan
Asif Loya, Iftikhar Ali Rana, Muhammad Tahseen, Muhammad Ishaq, Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab 54000, Pakistan
Muhammad Abu Bakar, Department of Cancer Registry and Clinical Data Management, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab 54000, Pakistan
Asim Farooq, Iqra Masood, Department of Clinical Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab 54000, Pakistan
Author contributions: Asghar K generated the hypotheses, designed experiments, carried out lab work and data analysis, and wrote the manuscript; Loya A evaluated the IHC slides and scored them, analyzed the data, and contributed to manuscript writing; Rana IA evaluated the IHC slides and scored them; Bakar MA and Farooq A conducted statistical analysis, analyzed data, and participated in writing the manuscript; Tahseen M and Ishaq M retrieved the blocks and performed IHC; Masood I performed patient data collection and verification from the electronic hospital information system and contributed to manuscript writing; Rashid MU assisted in hypothesis generation and critical appraisal of data.
Institutional review board statement: The study was reviewed and approved by the Shaukat Khanum Memorial Cancer Hospital and Research Centre Institutional Review Board.
Conflict-of-interest statement: Authors declare no conflict of interests for this manuscript.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at kashifasghar@skm.org.pk. Consent was not obtained but the presented data are anonymized and risk of identification is low. No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kashif Asghar, DVM, PhD, Research Scientist, Department of Basic Science Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, 7A, Block R3, Johar Town, Lahore, Punjab 54000, Pakistan. drkashifasghar@gmail.com
Received: April 13, 2020 Peer-review started: April 13, 2020 First decision: August 9, 2020 Revised: August 24, 2020 Accepted: October 27, 2020 Article in press: October 27, 2020 Published online: December 24, 2020 Processing time: 249 Days and 1.4 Hours
Abstract
BACKGROUND
Forkhead box P3 (FOXP3) is a specific marker for immunosuppressive regulatory T (T-reg) cells. T-regs and an immunosuppressive enzyme, indoleamine 2,3-dioxygenase (IDO), are associated with advanced disease in cancer.
AIM
To evaluate the co-expression of FOXP3 and IDO in triple negative breast cancer (TNBC) with respect to hormone-positive breast cancer patients from Pakistan.
METHODS
Immunohistochemistry was performed to analyze the expression of FOXP3, IDO, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor on tissues of breast cancer patients (n = 100): Hormone-positive breast cancer (n = 51) and TNBC (n = 49). A total of 100 patients were characterized as FOXP3 negative vs positive and further categorized based on low, medium, and high IDO expression score. Univariate and multivariate logistic regression models were used.
RESULTS
Out of 100 breast tumors, 25% expressed FOXP3 positive T-regs. A significant co-expression of FOXP3 and IDO was observed among patients with TNBC (P = 0.01) compared to those with hormone-positive breast cancer. Two variables were identified as significant independent risk factors for FOXP3 positive: IDO expression high (adjusted odds ratio (AOR) 5.90; 95% confidence interval (CI): 1.22-28.64; P = 0.03) and TNBC (AOR 2.80; 95%CI: 0.96-7.95; P = 0.05).
CONCLUSION
Our data showed that FOXP3 positive cells might be associated with high expression of IDO in TNBC patients. FOXP3 and IDO co-expression may also suggest its involvement in disease, and evaluation of FOXP3 and IDO expression in TNBC patients may offer a new therapeutic option.
Core Tip: Forkhead box P3 (FOXP3) positive cells might be associated with high expression of indoleamine 2,3-dioxygenase (IDO) in triple negative breast cancer (TNBC) patients. Evaluation of FOXP3 and IDO expression in TNBC patients may provide a novel effective therapeutic strategy.
