New Insights on Old Biomarkers Involved in Tumor Microenvironment Changes and Their Diagnostic Relevance in Non-Small Cell Lung Carcinoma
Background: Lung cancer is a multifactorial disease with a heterogeneous tumor group that hampers diagnostic and therapeutic approaches, as well as understanding of the processes that underlie its pathogenesis. Current research efforts are focused on examining alterations in the tumor microenvironme...
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MDPI AG
2021-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/8/1208 |
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| author | Katarzyna Wadowska Piotr Błasiak Adam Rzechonek Iwona Bil-Lula Mariola Śliwińska-Mossoń |
| author_facet | Katarzyna Wadowska Piotr Błasiak Adam Rzechonek Iwona Bil-Lula Mariola Śliwińska-Mossoń |
| author_sort | Katarzyna Wadowska |
| collection | DOAJ |
| description | Background: Lung cancer is a multifactorial disease with a heterogeneous tumor group that hampers diagnostic and therapeutic approaches, as well as understanding of the processes that underlie its pathogenesis. Current research efforts are focused on examining alterations in the tumor microenvironment, which may affect the pathogenesis and further malignant progression in lung cancer. The aim of this study was to investigate changes in the levels of biomarkers involved in the lung tumor microenvironment and their diagnostic utility in differentiating lung cancer subtypes and stages. Methods: This study comprised 112 lung cancer patients, 50 with adenocarcinoma, 35 with squamous cell carcinoma, 13 with other non-small cell lung carcinoma subtypes, and 14 with other lung neoplasms than non-small cell lung carcinoma. Tumor markers (CEA, CYFRA 21-1, and NSE) were measured in the patients’ sera and plasmas, along with IL-6, TNF-α, SAA<sub>1</sub>, CRP, MMP-2, MMP-9, glucose, lactate, and LDH, utilizing enzyme-linked immunosorbent assays, enzyme immunoassays, and automated clinical chemistry and turbidimetry systems. The results were statistically analyzed across patient groups based on the subtype and stage of lung cancer. Results: Glucose concentrations showed statistically significant (<i>p</i> < 0.05) differences both between lung cancer subtypes and stages, with the highest levels in patients with other lung neoplasms (me = 130.5 mg/dL) and in patients with stage IIB lung cancer (me = 132.0 mg/dL). In patients with advanced lung cancer, IL-6 and LDH had considerably higher concentration and activity. There was also a significant positive correlation between IL-6 and MMP-9 in adenocarcinoma and SqCC, with correlation coefficients of 0.53 and 0.49, respectively. The ROC analyses showed that the best single biomarkers for distinguishing adenocarcinoma from squamous cell carcinoma are glucose, CRP, and CYFRA 21-1; however, their combination did not significantly improve sensitivity, specificity, and the AUC value. The combinations of IL-6, glucose, LDH and CEA, IL-6, SAA1, MMP-9, and lactate can distinguish patients with stage IIB lung cancer from those with stage IIA with 100% sensitivity, 100% specificity, and with an AUC value of 0.8333 and 1.0000, respectively, whereas the combination of CEA, IL-6, and LDH can identify patients with stage IIIA lung cancer from those with stage IIB with 72.73% sensitivity, 94.44% specificity, and an AUC value of 0.8686. Conclusion: There is a link between biomarkers of tumor microenvironment changes and tumor markers, and combinations of these markers may be clinically useful in the differential diagnosis of adenocarcinoma and squamous cell carcinoma, as well as lung cancer stages IIB and IIA, and IIIA and IIB. |
| first_indexed | 2024-03-10T08:58:36Z |
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| id | doaj.art-911321b4021340598616cee58a5782bf |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T08:58:36Z |
| publishDate | 2021-08-01 |
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| spelling | doaj.art-911321b4021340598616cee58a5782bf2023-11-22T06:56:23ZengMDPI AGBiomolecules2218-273X2021-08-01118120810.3390/biom11081208New Insights on Old Biomarkers Involved in Tumor Microenvironment Changes and Their Diagnostic Relevance in Non-Small Cell Lung CarcinomaKatarzyna Wadowska0Piotr Błasiak1Adam Rzechonek2Iwona Bil-Lula3Mariola Śliwińska-Mossoń4Department of Medical Laboratory Diagnostics, Division of Clinical Chemistry and Laboratory Haematology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, PolandDepartment and Clinic of Thoracic Surgery, Wroclaw Medical University, Grabiszyńska 105, 53-439 Wroclaw, PolandDepartment and Clinic of Thoracic Surgery, Wroclaw Medical University, Grabiszyńska 105, 53-439 Wroclaw, PolandDepartment of Medical Laboratory Diagnostics, Division of Clinical Chemistry and Laboratory Haematology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, PolandDepartment of Medical Laboratory Diagnostics, Division of Clinical Chemistry and Laboratory Haematology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, PolandBackground: Lung cancer is a multifactorial disease with a heterogeneous tumor group that hampers diagnostic and therapeutic approaches, as well as understanding of the processes that underlie its pathogenesis. Current research efforts are focused on examining alterations in the tumor microenvironment, which may affect the pathogenesis and further malignant progression in lung cancer. The aim of this study was to investigate changes in the levels of biomarkers involved in the lung tumor microenvironment and their diagnostic utility in differentiating lung cancer subtypes and stages. Methods: This study comprised 112 lung cancer patients, 50 with adenocarcinoma, 35 with squamous cell carcinoma, 13 with other non-small cell lung carcinoma subtypes, and 14 with other lung neoplasms than non-small cell lung carcinoma. Tumor markers (CEA, CYFRA 21-1, and NSE) were measured in the patients’ sera and plasmas, along with IL-6, TNF-α, SAA<sub>1</sub>, CRP, MMP-2, MMP-9, glucose, lactate, and LDH, utilizing enzyme-linked immunosorbent assays, enzyme immunoassays, and automated clinical chemistry and turbidimetry systems. The results were statistically analyzed across patient groups based on the subtype and stage of lung cancer. Results: Glucose concentrations showed statistically significant (<i>p</i> < 0.05) differences both between lung cancer subtypes and stages, with the highest levels in patients with other lung neoplasms (me = 130.5 mg/dL) and in patients with stage IIB lung cancer (me = 132.0 mg/dL). In patients with advanced lung cancer, IL-6 and LDH had considerably higher concentration and activity. There was also a significant positive correlation between IL-6 and MMP-9 in adenocarcinoma and SqCC, with correlation coefficients of 0.53 and 0.49, respectively. The ROC analyses showed that the best single biomarkers for distinguishing adenocarcinoma from squamous cell carcinoma are glucose, CRP, and CYFRA 21-1; however, their combination did not significantly improve sensitivity, specificity, and the AUC value. The combinations of IL-6, glucose, LDH and CEA, IL-6, SAA1, MMP-9, and lactate can distinguish patients with stage IIB lung cancer from those with stage IIA with 100% sensitivity, 100% specificity, and with an AUC value of 0.8333 and 1.0000, respectively, whereas the combination of CEA, IL-6, and LDH can identify patients with stage IIIA lung cancer from those with stage IIB with 72.73% sensitivity, 94.44% specificity, and an AUC value of 0.8686. Conclusion: There is a link between biomarkers of tumor microenvironment changes and tumor markers, and combinations of these markers may be clinically useful in the differential diagnosis of adenocarcinoma and squamous cell carcinoma, as well as lung cancer stages IIB and IIA, and IIIA and IIB.https://www.mdpi.com/2218-273X/11/8/1208lung cancernon-small cell lung carcinomaadenocarcinoma of lungsquamous cell carcinoma of lungtumor microenvironmentmalignant progression |
| spellingShingle | Katarzyna Wadowska Piotr Błasiak Adam Rzechonek Iwona Bil-Lula Mariola Śliwińska-Mossoń New Insights on Old Biomarkers Involved in Tumor Microenvironment Changes and Their Diagnostic Relevance in Non-Small Cell Lung Carcinoma Biomolecules lung cancer non-small cell lung carcinoma adenocarcinoma of lung squamous cell carcinoma of lung tumor microenvironment malignant progression |
| title | New Insights on Old Biomarkers Involved in Tumor Microenvironment Changes and Their Diagnostic Relevance in Non-Small Cell Lung Carcinoma |
| title_full | New Insights on Old Biomarkers Involved in Tumor Microenvironment Changes and Their Diagnostic Relevance in Non-Small Cell Lung Carcinoma |
| title_fullStr | New Insights on Old Biomarkers Involved in Tumor Microenvironment Changes and Their Diagnostic Relevance in Non-Small Cell Lung Carcinoma |
| title_full_unstemmed | New Insights on Old Biomarkers Involved in Tumor Microenvironment Changes and Their Diagnostic Relevance in Non-Small Cell Lung Carcinoma |
| title_short | New Insights on Old Biomarkers Involved in Tumor Microenvironment Changes and Their Diagnostic Relevance in Non-Small Cell Lung Carcinoma |
| title_sort | new insights on old biomarkers involved in tumor microenvironment changes and their diagnostic relevance in non small cell lung carcinoma |
| topic | lung cancer non-small cell lung carcinoma adenocarcinoma of lung squamous cell carcinoma of lung tumor microenvironment malignant progression |
| url | https://www.mdpi.com/2218-273X/11/8/1208 |
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