In Lower‐Grade Gliomas, the SPARC Family Exacerbates Prognosis by Influencing Immunity, Stemness, and Metabolism
ABSTRACT Background Involvement of the SPARC stromal protein family in crucial biological regulatory mechanisms is well‐documented. But understanding the consequences of imbalanced SPARC protein activity in lower‐grade glioma (LGG) is still emerging. Aims Examining the clinical significance of SPARC...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-08-01
|
| Series: | Cancer Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cnr2.70307 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849222375126597632 |
|---|---|
| author | Qiaoying Peng Wenxia Zhou Ying Chen Yong Cai |
| author_facet | Qiaoying Peng Wenxia Zhou Ying Chen Yong Cai |
| author_sort | Qiaoying Peng |
| collection | DOAJ |
| description | ABSTRACT Background Involvement of the SPARC stromal protein family in crucial biological regulatory mechanisms is well‐documented. But understanding the consequences of imbalanced SPARC protein activity in lower‐grade glioma (LGG) is still emerging. Aims Examining the clinical significance of SPARC proteins, researchers employed RNA‐seq data from diverse patient groups to gain insight. A novel SPARCScore was developed via LASSO regression analysis, leveraging data from the PanCanAtlas and MEXPRESS to shed light on the molecular mechanisms involved. Methods and Results Our findings indicate that a majority of SPARC family proteins show atypical expression levels, correlating significantly with adverse outcomes in LGG. Our construction of an SPARCscore, indicative of the SPARC family's presence, revealed a direct correlation between a high SPARCscore and worsened tumor prognosis, irrespective of radiotherapy or chemotherapy treatments. The SPARCScore risk groups showed distinct drivers: PIK3CA predominantly influenced the low‐risk category, whereas EGFR was a key factor in the high‐risk group. High SPARCScore tumors exhibited a mutation profile similar to glioblastoma, marked by reduced methylation and diverse glioma stem cells (GSC). Conversely, the low SPARCScore tumors were characterized by increased methylation and limited GSC variety. Furthermore, the high‐SPARCScore group was notable for its pronounced inflammatory and extracellular matrix signatures, along with activated metabolic pathways. These patterns were closely linked to prognosis. Conclusion In essence, this research highlights the significance of SPARC proteins in LGG, offering insights into promising avenues for targeted therapy. |
| format | Article |
| id | doaj-art-29bac2df5ca64124856f2d1c37bd8e64 |
| institution | Kabale University |
| issn | 2573-8348 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Reports |
| spelling | doaj-art-29bac2df5ca64124856f2d1c37bd8e642025-08-26T06:00:41ZengWileyCancer Reports2573-83482025-08-0188n/an/a10.1002/cnr2.70307In Lower‐Grade Gliomas, the SPARC Family Exacerbates Prognosis by Influencing Immunity, Stemness, and MetabolismQiaoying Peng0Wenxia Zhou1Ying Chen2Yong Cai3Department of Operation Room (OR), The First People's Hospital of Huzhou Affiliated Hospital of Huzhou Teachers College Huzhou ChinaDepartment of Operation Room (OR), The First People's Hospital of Huzhou Affiliated Hospital of Huzhou Teachers College Huzhou ChinaDepartment of Operation Room (OR), The First People's Hospital of Huzhou Affiliated Hospital of Huzhou Teachers College Huzhou ChinaDepartment of Operation Room (OR), The First People's Hospital of Huzhou Affiliated Hospital of Huzhou Teachers College Huzhou ChinaABSTRACT Background Involvement of the SPARC stromal protein family in crucial biological regulatory mechanisms is well‐documented. But understanding the consequences of imbalanced SPARC protein activity in lower‐grade glioma (LGG) is still emerging. Aims Examining the clinical significance of SPARC proteins, researchers employed RNA‐seq data from diverse patient groups to gain insight. A novel SPARCScore was developed via LASSO regression analysis, leveraging data from the PanCanAtlas and MEXPRESS to shed light on the molecular mechanisms involved. Methods and Results Our findings indicate that a majority of SPARC family proteins show atypical expression levels, correlating significantly with adverse outcomes in LGG. Our construction of an SPARCscore, indicative of the SPARC family's presence, revealed a direct correlation between a high SPARCscore and worsened tumor prognosis, irrespective of radiotherapy or chemotherapy treatments. The SPARCScore risk groups showed distinct drivers: PIK3CA predominantly influenced the low‐risk category, whereas EGFR was a key factor in the high‐risk group. High SPARCScore tumors exhibited a mutation profile similar to glioblastoma, marked by reduced methylation and diverse glioma stem cells (GSC). Conversely, the low SPARCScore tumors were characterized by increased methylation and limited GSC variety. Furthermore, the high‐SPARCScore group was notable for its pronounced inflammatory and extracellular matrix signatures, along with activated metabolic pathways. These patterns were closely linked to prognosis. Conclusion In essence, this research highlights the significance of SPARC proteins in LGG, offering insights into promising avenues for targeted therapy.https://doi.org/10.1002/cnr2.70307EMTGSCLGGmethylationSPARC |
| spellingShingle | Qiaoying Peng Wenxia Zhou Ying Chen Yong Cai In Lower‐Grade Gliomas, the SPARC Family Exacerbates Prognosis by Influencing Immunity, Stemness, and Metabolism Cancer Reports EMT GSC LGG methylation SPARC |
| title | In Lower‐Grade Gliomas, the SPARC Family Exacerbates Prognosis by Influencing Immunity, Stemness, and Metabolism |
| title_full | In Lower‐Grade Gliomas, the SPARC Family Exacerbates Prognosis by Influencing Immunity, Stemness, and Metabolism |
| title_fullStr | In Lower‐Grade Gliomas, the SPARC Family Exacerbates Prognosis by Influencing Immunity, Stemness, and Metabolism |
| title_full_unstemmed | In Lower‐Grade Gliomas, the SPARC Family Exacerbates Prognosis by Influencing Immunity, Stemness, and Metabolism |
| title_short | In Lower‐Grade Gliomas, the SPARC Family Exacerbates Prognosis by Influencing Immunity, Stemness, and Metabolism |
| title_sort | in lower grade gliomas the sparc family exacerbates prognosis by influencing immunity stemness and metabolism |
| topic | EMT GSC LGG methylation SPARC |
| url | https://doi.org/10.1002/cnr2.70307 |
| work_keys_str_mv | AT qiaoyingpeng inlowergradegliomasthesparcfamilyexacerbatesprognosisbyinfluencingimmunitystemnessandmetabolism AT wenxiazhou inlowergradegliomasthesparcfamilyexacerbatesprognosisbyinfluencingimmunitystemnessandmetabolism AT yingchen inlowergradegliomasthesparcfamilyexacerbatesprognosisbyinfluencingimmunitystemnessandmetabolism AT yongcai inlowergradegliomasthesparcfamilyexacerbatesprognosisbyinfluencingimmunitystemnessandmetabolism |