Carbonic Anhydrase IX Expression and Treatment Response Measured in Rectal Adenocarcinoma Following Neoadjuvant Chemo-Radiotherapy
The overexpression of the pH regulator carbonic anhydrase IX (CAIX) due to hypoxic/metabolic stress was reported in various tumors as an adverse prognostic feature. Our retrospective study aimed to investigate the general pattern and dynamics of CAIX expression in rectal adenocarcinoma following pre...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2581 |
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| author | Emese Sarolta Bádon Lívia Beke Attila Mokánszki Csilla András Gábor Méhes |
| author_facet | Emese Sarolta Bádon Lívia Beke Attila Mokánszki Csilla András Gábor Méhes |
| author_sort | Emese Sarolta Bádon |
| collection | DOAJ |
| description | The overexpression of the pH regulator carbonic anhydrase IX (CAIX) due to hypoxic/metabolic stress was reported in various tumors as an adverse prognostic feature. Our retrospective study aimed to investigate the general pattern and dynamics of CAIX expression in rectal adenocarcinoma following preoperative neoadjuvant therapy (NAT) in matched initial biopsy and surgical resection samples. A total of 40/55 (72.72%) of the post-treatment samples showed partial CAIX expression, frequently in the proximity of hypoxic tumor areas. CAIX expression showed a significant increase in post-treatment tumors (mean% 21.8 ± 24.9 SD vs. 39.4 ± 29.4 SD, <i>p</i> < 0.0001), that was not obvious in untreated tumors (mean% 15.0 ± 21.3 SD vs. 20 ± 23.02, <i>p</i> = 0.073). CAIXhigh phenotype was associated with mutant <i>KRAS</i> status and lack of pathological regression (WHO Tumor Regression Grade 4 and 5). However, the adverse effect of CAIX on overall or progression-free survival could not be statistically confirmed. In conclusion, the dynamic upregulation of CAIX expression is a general feature of rectal adenocarcinoma following neoadjuvant chemo-radiotherapy indicating therapy-induced metabolic reprogramming and cellular adaptation. A synergism of the CAIX-associated regulatory pathways and the mutant <i>KRAS</i> oncogenic signaling most likely contributes to therapy resistance and survival of residual cancer. |
| first_indexed | 2024-03-11T09:40:29Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:40:29Z |
| publishDate | 2023-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-079b2472688845b885b69547e34263882023-11-16T16:59:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243258110.3390/ijms24032581Carbonic Anhydrase IX Expression and Treatment Response Measured in Rectal Adenocarcinoma Following Neoadjuvant Chemo-RadiotherapyEmese Sarolta Bádon0Lívia Beke1Attila Mokánszki2Csilla András3Gábor Méhes4Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Oncology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryThe overexpression of the pH regulator carbonic anhydrase IX (CAIX) due to hypoxic/metabolic stress was reported in various tumors as an adverse prognostic feature. Our retrospective study aimed to investigate the general pattern and dynamics of CAIX expression in rectal adenocarcinoma following preoperative neoadjuvant therapy (NAT) in matched initial biopsy and surgical resection samples. A total of 40/55 (72.72%) of the post-treatment samples showed partial CAIX expression, frequently in the proximity of hypoxic tumor areas. CAIX expression showed a significant increase in post-treatment tumors (mean% 21.8 ± 24.9 SD vs. 39.4 ± 29.4 SD, <i>p</i> < 0.0001), that was not obvious in untreated tumors (mean% 15.0 ± 21.3 SD vs. 20 ± 23.02, <i>p</i> = 0.073). CAIXhigh phenotype was associated with mutant <i>KRAS</i> status and lack of pathological regression (WHO Tumor Regression Grade 4 and 5). However, the adverse effect of CAIX on overall or progression-free survival could not be statistically confirmed. In conclusion, the dynamic upregulation of CAIX expression is a general feature of rectal adenocarcinoma following neoadjuvant chemo-radiotherapy indicating therapy-induced metabolic reprogramming and cellular adaptation. A synergism of the CAIX-associated regulatory pathways and the mutant <i>KRAS</i> oncogenic signaling most likely contributes to therapy resistance and survival of residual cancer.https://www.mdpi.com/1422-0067/24/3/2581rectal adenocarcinomaneoadjuvant treatmentCAIX expression<i>KRAS</i> status |
| spellingShingle | Emese Sarolta Bádon Lívia Beke Attila Mokánszki Csilla András Gábor Méhes Carbonic Anhydrase IX Expression and Treatment Response Measured in Rectal Adenocarcinoma Following Neoadjuvant Chemo-Radiotherapy International Journal of Molecular Sciences rectal adenocarcinoma neoadjuvant treatment CAIX expression <i>KRAS</i> status |
| title | Carbonic Anhydrase IX Expression and Treatment Response Measured in Rectal Adenocarcinoma Following Neoadjuvant Chemo-Radiotherapy |
| title_full | Carbonic Anhydrase IX Expression and Treatment Response Measured in Rectal Adenocarcinoma Following Neoadjuvant Chemo-Radiotherapy |
| title_fullStr | Carbonic Anhydrase IX Expression and Treatment Response Measured in Rectal Adenocarcinoma Following Neoadjuvant Chemo-Radiotherapy |
| title_full_unstemmed | Carbonic Anhydrase IX Expression and Treatment Response Measured in Rectal Adenocarcinoma Following Neoadjuvant Chemo-Radiotherapy |
| title_short | Carbonic Anhydrase IX Expression and Treatment Response Measured in Rectal Adenocarcinoma Following Neoadjuvant Chemo-Radiotherapy |
| title_sort | carbonic anhydrase ix expression and treatment response measured in rectal adenocarcinoma following neoadjuvant chemo radiotherapy |
| topic | rectal adenocarcinoma neoadjuvant treatment CAIX expression <i>KRAS</i> status |
| url | https://www.mdpi.com/1422-0067/24/3/2581 |
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