Identification and Validation of Serum CST1 as a Diagnostic Marker for Differentiating Early-Stage Non-Small Cell Lung Cancer from Pulmonary Benign Nodules
Background Effective means for early diagnosis are imperative to reduce death rate of non-small cell lung cancer (NSCLC) patients. We aimed to find out high-performance serologic markers to distinguish early-stage NSCLC patients from benign pulmonary nodule patients and healthy controls (HC). Cystat...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2022-05-01
|
| Series: | Cancer Control |
| Online Access: | https://doi.org/10.1177/10732748221104661 |
| _version_ | 1818199693338869760 |
|---|---|
| author | Yanzhen Lai MM Yu Wang MM Yaxian Wu MM Meng Wu MM Shan Xing MM Ying Xie MD Shulin Chen MM Xiaohui Li MM Ao Zhang MD Yi He MD Huilan Li MM Shuqin Dai MM Junye Wang MM Shudai Lin MM Yunmeng Bai MM Hongli Du PhD Wanli Liu MD, PhD |
| author_facet | Yanzhen Lai MM Yu Wang MM Yaxian Wu MM Meng Wu MM Shan Xing MM Ying Xie MD Shulin Chen MM Xiaohui Li MM Ao Zhang MD Yi He MD Huilan Li MM Shuqin Dai MM Junye Wang MM Shudai Lin MM Yunmeng Bai MM Hongli Du PhD Wanli Liu MD, PhD |
| author_sort | Yanzhen Lai MM |
| collection | DOAJ |
| description | Background Effective means for early diagnosis are imperative to reduce death rate of non-small cell lung cancer (NSCLC) patients. We aimed to find out high-performance serologic markers to distinguish early-stage NSCLC patients from benign pulmonary nodule patients and healthy controls (HC). Cystatin-SN (CST1) is an active cysteine protease inhibitor of the CST superfamily, involving in the processes of inflammation and tumorigenesis. This is the first exploration of the diagnostic and prognostic values of serum CST1 in NSCLC. Methods We analyzed the transcriptome data from The Cancer Genome Atlas and the Gene Expression Omnibus database, screened biomarkers for NSCLC, and verified the candidate markers via the ONCOMINE database. Then, we performed ELISA, western blotting, and immunohistochemistry analysis to detect the expression levels of CST1 in NSCLC cell lines, tumor tissues, and serum samples of clinical cohorts. Results We identified 3 up-regulated secreted protein-encoding genes, validated the expression levels of CST1 in NSCLC tumor tissues and cell lines, and found that serum CST1 levels of NSCLC (4289 ± 2405 pg/mL) were significantly higher than those of PBN patients (1558 ± 441 pg/mL, P < .0001) and healthy controls (1529 ± 416 pg/mL, P < .0001). The AUC of the combination of CST1, Cytokeratin 19 fragment (Cyfra21-1), and Carcinoembryonic antigen (CEA) for distinguishing early-stage NSCLC from PBN/HC was as high as .914/0.925. Furthermore, our results suggested that the NSCLC patient with low serum CST1 level had a better survival rate. Conclusions Serum CST1 may serve as a novel diagnostic marker for differentiating early-stage NSCLC from PBN and HC, and could be used as a prognosis predictor in NSCLC patients. |
| first_indexed | 2024-12-12T02:25:49Z |
| format | Article |
| id | doaj.art-4ce634125b614ef89e8e791e4b11e46a |
| institution | Directory Open Access Journal |
| issn | 1073-2748 |
| language | English |
| last_indexed | 2024-12-12T02:25:49Z |
| publishDate | 2022-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cancer Control |
| spelling | doaj.art-4ce634125b614ef89e8e791e4b11e46a2022-12-22T00:41:33ZengSAGE PublishingCancer Control1073-27482022-05-012910.1177/10732748221104661Identification and Validation of Serum CST1 as a Diagnostic Marker for Differentiating Early-Stage Non-Small Cell Lung Cancer from Pulmonary Benign NodulesYanzhen Lai MMYu Wang MMYaxian Wu MMMeng Wu MMShan Xing MMYing Xie MDShulin Chen MMXiaohui Li MMAo Zhang MDYi He MDHuilan Li MMShuqin Dai MMJunye Wang MMShudai Lin MMYunmeng Bai MMHongli Du PhDWanli Liu MD, PhDBackground Effective means for early diagnosis are imperative to reduce death rate of non-small cell lung cancer (NSCLC) patients. We aimed to find out high-performance serologic markers to distinguish early-stage NSCLC patients from benign pulmonary nodule patients and healthy controls (HC). Cystatin-SN (CST1) is an active cysteine protease inhibitor of the CST superfamily, involving in the processes of inflammation and tumorigenesis. This is the first exploration of the diagnostic and prognostic values of serum CST1 in NSCLC. Methods We analyzed the transcriptome data from The Cancer Genome Atlas and the Gene Expression Omnibus database, screened biomarkers for NSCLC, and verified the candidate markers via the ONCOMINE database. Then, we performed ELISA, western blotting, and immunohistochemistry analysis to detect the expression levels of CST1 in NSCLC cell lines, tumor tissues, and serum samples of clinical cohorts. Results We identified 3 up-regulated secreted protein-encoding genes, validated the expression levels of CST1 in NSCLC tumor tissues and cell lines, and found that serum CST1 levels of NSCLC (4289 ± 2405 pg/mL) were significantly higher than those of PBN patients (1558 ± 441 pg/mL, P < .0001) and healthy controls (1529 ± 416 pg/mL, P < .0001). The AUC of the combination of CST1, Cytokeratin 19 fragment (Cyfra21-1), and Carcinoembryonic antigen (CEA) for distinguishing early-stage NSCLC from PBN/HC was as high as .914/0.925. Furthermore, our results suggested that the NSCLC patient with low serum CST1 level had a better survival rate. Conclusions Serum CST1 may serve as a novel diagnostic marker for differentiating early-stage NSCLC from PBN and HC, and could be used as a prognosis predictor in NSCLC patients.https://doi.org/10.1177/10732748221104661 |
| spellingShingle | Yanzhen Lai MM Yu Wang MM Yaxian Wu MM Meng Wu MM Shan Xing MM Ying Xie MD Shulin Chen MM Xiaohui Li MM Ao Zhang MD Yi He MD Huilan Li MM Shuqin Dai MM Junye Wang MM Shudai Lin MM Yunmeng Bai MM Hongli Du PhD Wanli Liu MD, PhD Identification and Validation of Serum CST1 as a Diagnostic Marker for Differentiating Early-Stage Non-Small Cell Lung Cancer from Pulmonary Benign Nodules Cancer Control |
| title | Identification and Validation of Serum CST1 as a Diagnostic Marker for Differentiating Early-Stage Non-Small Cell Lung Cancer from Pulmonary Benign Nodules |
| title_full | Identification and Validation of Serum CST1 as a Diagnostic Marker for Differentiating Early-Stage Non-Small Cell Lung Cancer from Pulmonary Benign Nodules |
| title_fullStr | Identification and Validation of Serum CST1 as a Diagnostic Marker for Differentiating Early-Stage Non-Small Cell Lung Cancer from Pulmonary Benign Nodules |
| title_full_unstemmed | Identification and Validation of Serum CST1 as a Diagnostic Marker for Differentiating Early-Stage Non-Small Cell Lung Cancer from Pulmonary Benign Nodules |
| title_short | Identification and Validation of Serum CST1 as a Diagnostic Marker for Differentiating Early-Stage Non-Small Cell Lung Cancer from Pulmonary Benign Nodules |
| title_sort | identification and validation of serum cst1 as a diagnostic marker for differentiating early stage non small cell lung cancer from pulmonary benign nodules |
| url | https://doi.org/10.1177/10732748221104661 |
| work_keys_str_mv | AT yanzhenlaimm identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT yuwangmm identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT yaxianwumm identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT mengwumm identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT shanxingmm identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT yingxiemd identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT shulinchenmm identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT xiaohuilimm identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT aozhangmd identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT yihemd identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT huilanlimm identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT shuqindaimm identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT junyewangmm identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT shudailinmm identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT yunmengbaimm identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT hongliduphd identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules AT wanliliumdphd identificationandvalidationofserumcst1asadiagnosticmarkerfordifferentiatingearlystagenonsmallcelllungcancerfrompulmonarybenignnodules |