Diagnostic, prognostic and treatment response of perilipin1 gene in breast cancer
Background: Genetic alterations in the perilipin (PLIN) family genes (PLIN1 to PLIN5) were infrequent in breast cancer (BC) where enhanced levels of PLIN1, PLIN3-5 were observed in the luminal A and luminal B subgroups, whereas increased PLIN2 expression was observed in the HER2-enriched and basal-l...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-05-01
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| Series: | Journal of King Saud University: Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1018364724000739 |
| _version_ | 1797210095028797440 |
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| author | Sajjad Karim Md Shahid Iqbal Fadwa Aljoud Najla Ali Alburae Zoya Nisar Nofe Alganmi Haneen Banjar Zeenat Mirza |
| author_facet | Sajjad Karim Md Shahid Iqbal Fadwa Aljoud Najla Ali Alburae Zoya Nisar Nofe Alganmi Haneen Banjar Zeenat Mirza |
| author_sort | Sajjad Karim |
| collection | DOAJ |
| description | Background: Genetic alterations in the perilipin (PLIN) family genes (PLIN1 to PLIN5) were infrequent in breast cancer (BC) where enhanced levels of PLIN1, PLIN3-5 were observed in the luminal A and luminal B subgroups, whereas increased PLIN2 expression was observed in the HER2-enriched and basal-like subgroups. However, the predictive value of PLIN1 for BC patient outcomes remains uncertain. In the present study, we aim to investigate the diagnostic, prognostic and treatment response roles of the PLIN1 gene expression in BC. Methods: We obtained microarray BC trancriptomic data of 320 tumor (T) and 62 normal (N) breast samples from five GEO data-series; GSE7904 (38 T:7N), GSE42568 (101 T: 15 N), GSE26910 (6 T:6N), GSE45827 (144 T:7N), and GSE10810 (31 T:27 N). The Welch t test was used to analyze the significant differences in gene expression including PLIN1 with fold change > ±2 and p-value < 0.05. The expression of PLIN1 was confirmed by RTqPCR using clinical specimen samples from BC patients. The Kaplan-Meier Plotter was used to assess survival on large independent dataset (31 dataset for relapse-free survival and 14 datasets for overall survival) and significance was determined by calculating hazard ratios (>1) and log-rank p-values < 0.05. We also assessed the treatment outcomes of endocrine therapy (tamoxifen and aromatase-inhibitors), anti-HER2 therapy (trastuzumab and lapatinib), and chemotherapy (taxane, anthracycline, and ixabepilone) using robust statistical methods and correlated with PLIN1 gene expression. Results: We identified significantly reduced expression of PLIN1 (FC = −30.76, p value = 2.183e−24) in BC samples compared with normal controls. Our qPCR result confirmed the microarray expression pattern of PLIN1 in BC. Survival analysis revealed PLIN1 to be a moderately important prognostic biomarker. Our findings highlight the effectiveness of trastuzumab and anthracycline in classifying treatment responses, supported by Mann-Whitney tests indicating statistical significance in gene expression differences between responders and non-responders. Conclusion: In conclusion, our findings indicate that PLIN1 is one of the most down-regulated genes and a moderately important biomarker in BC for prognostic purposes. PLIN1 was a good indicator of trastuzumab and anthracycline treatment responses in BC. |
| first_indexed | 2024-04-24T10:05:08Z |
| format | Article |
| id | doaj.art-46b53bf3e8ca4b499c7072c928c56321 |
| institution | Directory Open Access Journal |
| issn | 1018-3647 |
| language | English |
| last_indexed | 2024-04-24T10:05:08Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of King Saud University: Science |
| spelling | doaj.art-46b53bf3e8ca4b499c7072c928c563212024-04-13T04:20:58ZengElsevierJournal of King Saud University: Science1018-36472024-05-01365103161Diagnostic, prognostic and treatment response of perilipin1 gene in breast cancerSajjad Karim0Md Shahid Iqbal1Fadwa Aljoud2Najla Ali Alburae3Zoya Nisar4Nofe Alganmi5Haneen Banjar6Zeenat Mirza7Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Science, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; Corresponding author at: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.University Department of Statistics and Computer Applications, T. M. Bhagalpur University, Bhagalpur, IndiaDepartment of Biology, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biology, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaUniversity Department of Psychology, Aligarh Muslim University, Aligarh, IndiaCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; Computer Science Department, Faculty of Computing and Information Technology, King Abdulaziz University, Jeddah, Saudi Arabia; Centre of Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah, Saudi ArabiaCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; Computer Science Department, Faculty of Computing and Information Technology, King Abdulaziz University, Jeddah, Saudi Arabia; Centre of Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Medical Laboratory Science, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi ArabiaBackground: Genetic alterations in the perilipin (PLIN) family genes (PLIN1 to PLIN5) were infrequent in breast cancer (BC) where enhanced levels of PLIN1, PLIN3-5 were observed in the luminal A and luminal B subgroups, whereas increased PLIN2 expression was observed in the HER2-enriched and basal-like subgroups. However, the predictive value of PLIN1 for BC patient outcomes remains uncertain. In the present study, we aim to investigate the diagnostic, prognostic and treatment response roles of the PLIN1 gene expression in BC. Methods: We obtained microarray BC trancriptomic data of 320 tumor (T) and 62 normal (N) breast samples from five GEO data-series; GSE7904 (38 T:7N), GSE42568 (101 T: 15 N), GSE26910 (6 T:6N), GSE45827 (144 T:7N), and GSE10810 (31 T:27 N). The Welch t test was used to analyze the significant differences in gene expression including PLIN1 with fold change > ±2 and p-value < 0.05. The expression of PLIN1 was confirmed by RTqPCR using clinical specimen samples from BC patients. The Kaplan-Meier Plotter was used to assess survival on large independent dataset (31 dataset for relapse-free survival and 14 datasets for overall survival) and significance was determined by calculating hazard ratios (>1) and log-rank p-values < 0.05. We also assessed the treatment outcomes of endocrine therapy (tamoxifen and aromatase-inhibitors), anti-HER2 therapy (trastuzumab and lapatinib), and chemotherapy (taxane, anthracycline, and ixabepilone) using robust statistical methods and correlated with PLIN1 gene expression. Results: We identified significantly reduced expression of PLIN1 (FC = −30.76, p value = 2.183e−24) in BC samples compared with normal controls. Our qPCR result confirmed the microarray expression pattern of PLIN1 in BC. Survival analysis revealed PLIN1 to be a moderately important prognostic biomarker. Our findings highlight the effectiveness of trastuzumab and anthracycline in classifying treatment responses, supported by Mann-Whitney tests indicating statistical significance in gene expression differences between responders and non-responders. Conclusion: In conclusion, our findings indicate that PLIN1 is one of the most down-regulated genes and a moderately important biomarker in BC for prognostic purposes. PLIN1 was a good indicator of trastuzumab and anthracycline treatment responses in BC.http://www.sciencedirect.com/science/article/pii/S1018364724000739Breast cancerPLIN1 geneGene expressionWelch testKaplan-Meier survival plotLancaster |
| spellingShingle | Sajjad Karim Md Shahid Iqbal Fadwa Aljoud Najla Ali Alburae Zoya Nisar Nofe Alganmi Haneen Banjar Zeenat Mirza Diagnostic, prognostic and treatment response of perilipin1 gene in breast cancer Journal of King Saud University: Science Breast cancer PLIN1 gene Gene expression Welch test Kaplan-Meier survival plot Lancaster |
| title | Diagnostic, prognostic and treatment response of perilipin1 gene in breast cancer |
| title_full | Diagnostic, prognostic and treatment response of perilipin1 gene in breast cancer |
| title_fullStr | Diagnostic, prognostic and treatment response of perilipin1 gene in breast cancer |
| title_full_unstemmed | Diagnostic, prognostic and treatment response of perilipin1 gene in breast cancer |
| title_short | Diagnostic, prognostic and treatment response of perilipin1 gene in breast cancer |
| title_sort | diagnostic prognostic and treatment response of perilipin1 gene in breast cancer |
| topic | Breast cancer PLIN1 gene Gene expression Welch test Kaplan-Meier survival plot Lancaster |
| url | http://www.sciencedirect.com/science/article/pii/S1018364724000739 |
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