Txnrd1 as a prognosticator for recurrence, metastasis and response to neoadjuvant chemotherapy and radiotherapy in breast cancer patients
Thioredoxin reductase 1 (Txnrd1) is known to have prognostic significance in a subset of breast cancer patients. Despite the pivotal role of Txnrd1 in regulating several cellular and physiological processes in cancer progression and metastasis, its clinical significance is largely unrecognized. Here...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024030421 |
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| author | Raghavendra S. Patwardhan Archita Rai Deepak Sharma Santosh K. Sandur Sejal Patwardhan |
| author_facet | Raghavendra S. Patwardhan Archita Rai Deepak Sharma Santosh K. Sandur Sejal Patwardhan |
| author_sort | Raghavendra S. Patwardhan |
| collection | DOAJ |
| description | Thioredoxin reductase 1 (Txnrd1) is known to have prognostic significance in a subset of breast cancer patients. Despite the pivotal role of Txnrd1 in regulating several cellular and physiological processes in cancer progression and metastasis, its clinical significance is largely unrecognized. Here, we undertook a retrospective comprehensive meta-analysis of 13,322 breast cancer patients from 43 independent cohorts to assess prognostic and predictive roles of Txnrd1. We observed that Txnrd1 has a positive correlation with tumor grade and size and it is over-expressed in higher-grade and larger tumors. Further, hormone receptor-negative and HER2-positive tumors exhibit elevated Txnrd1 gene expression. Patients with elevated Txnrd1 expression exhibit significant hazards for shorter disease-specific and overall survival. While Txnrd1 has a positive correlation with tumor recurrence and metastasis, it has a negative correlation with time to recurrence and metastasis. Txnrd1High patients exhibit 2.5 years early recurrence and 1.3 years early metastasis as compared to Txnrd1Low cohort. Interestingly, patients with high Txnrd1 gene expression exhibit a pathologic complete response (pCR) to neoadjuvant chemotherapy, but they experience early recurrence after radiotherapy. Txnrd1High MDA-MB-231 cells exhibit significant ROS generation and reduced viability after doxorubicin treatment compared to Txnrd1Low MCF7 cells. Corroborating with findings from meta-analysis, Txnrd1 depletion leads to decreased survival, enhanced sensitivity to radiation induced killing, poor scratch-wound healing, and reduced invasion potential in MDA-MB-231 cells. Thus, Txnrd1 appears to be a potential predictor of recurrence, metastasis and therapy response in breast cancer patients. |
| first_indexed | 2024-04-24T13:50:10Z |
| format | Article |
| id | doaj.art-31d68328d00b48ec89fb7e06f1957c99 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T13:50:10Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-31d68328d00b48ec89fb7e06f1957c992024-04-04T05:04:20ZengElsevierHeliyon2405-84402024-03-01106e27011Txnrd1 as a prognosticator for recurrence, metastasis and response to neoadjuvant chemotherapy and radiotherapy in breast cancer patientsRaghavendra S. Patwardhan0Archita Rai1Deepak Sharma2Santosh K. Sandur3Sejal Patwardhan4Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, IndiaRadiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India; Homi Bhabha National Institute, Mumbai, 400094, IndiaRadiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India; Homi Bhabha National Institute, Mumbai, 400094, IndiaRadiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India; Homi Bhabha National Institute, Mumbai, 400094, India; Corresponding author. Homi Bhabha National Institute Head, Free Radical Biology Section Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India.Homi Bhabha National Institute, Mumbai, 400094, India; Patwardhan Lab, Advanced Centre for Treatment Research & Education in Cancer, (ACTREC), Tata Memorial Centre (TMC), Kharghar, Navi Mumbai, 410210, India; Corresponding author. Homi Bhabha National Institute Principal Investigator, Patwardhan Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre (TMC) Kharghar, Navi Mumbai, 410210, India.Thioredoxin reductase 1 (Txnrd1) is known to have prognostic significance in a subset of breast cancer patients. Despite the pivotal role of Txnrd1 in regulating several cellular and physiological processes in cancer progression and metastasis, its clinical significance is largely unrecognized. Here, we undertook a retrospective comprehensive meta-analysis of 13,322 breast cancer patients from 43 independent cohorts to assess prognostic and predictive roles of Txnrd1. We observed that Txnrd1 has a positive correlation with tumor grade and size and it is over-expressed in higher-grade and larger tumors. Further, hormone receptor-negative and HER2-positive tumors exhibit elevated Txnrd1 gene expression. Patients with elevated Txnrd1 expression exhibit significant hazards for shorter disease-specific and overall survival. While Txnrd1 has a positive correlation with tumor recurrence and metastasis, it has a negative correlation with time to recurrence and metastasis. Txnrd1High patients exhibit 2.5 years early recurrence and 1.3 years early metastasis as compared to Txnrd1Low cohort. Interestingly, patients with high Txnrd1 gene expression exhibit a pathologic complete response (pCR) to neoadjuvant chemotherapy, but they experience early recurrence after radiotherapy. Txnrd1High MDA-MB-231 cells exhibit significant ROS generation and reduced viability after doxorubicin treatment compared to Txnrd1Low MCF7 cells. Corroborating with findings from meta-analysis, Txnrd1 depletion leads to decreased survival, enhanced sensitivity to radiation induced killing, poor scratch-wound healing, and reduced invasion potential in MDA-MB-231 cells. Thus, Txnrd1 appears to be a potential predictor of recurrence, metastasis and therapy response in breast cancer patients.http://www.sciencedirect.com/science/article/pii/S2405844024030421Thioredoxin reductaseNrf2ROSIonizing radiationTherapy response |
| spellingShingle | Raghavendra S. Patwardhan Archita Rai Deepak Sharma Santosh K. Sandur Sejal Patwardhan Txnrd1 as a prognosticator for recurrence, metastasis and response to neoadjuvant chemotherapy and radiotherapy in breast cancer patients Heliyon Thioredoxin reductase Nrf2 ROS Ionizing radiation Therapy response |
| title | Txnrd1 as a prognosticator for recurrence, metastasis and response to neoadjuvant chemotherapy and radiotherapy in breast cancer patients |
| title_full | Txnrd1 as a prognosticator for recurrence, metastasis and response to neoadjuvant chemotherapy and radiotherapy in breast cancer patients |
| title_fullStr | Txnrd1 as a prognosticator for recurrence, metastasis and response to neoadjuvant chemotherapy and radiotherapy in breast cancer patients |
| title_full_unstemmed | Txnrd1 as a prognosticator for recurrence, metastasis and response to neoadjuvant chemotherapy and radiotherapy in breast cancer patients |
| title_short | Txnrd1 as a prognosticator for recurrence, metastasis and response to neoadjuvant chemotherapy and radiotherapy in breast cancer patients |
| title_sort | txnrd1 as a prognosticator for recurrence metastasis and response to neoadjuvant chemotherapy and radiotherapy in breast cancer patients |
| topic | Thioredoxin reductase Nrf2 ROS Ionizing radiation Therapy response |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024030421 |
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