KRAS-related miR-143 expression is associated with lymph node involvement and correlates with outcome in pancreatic adenocarcinoma patients
IntroductionPancreatic adenocarcinoma (PC) is one of the most lethal malignancies; even after resection the patients’ 5-year disease-free survival (DFS) is lower than 26%. The genetic mutational landscape of PC is dominated by activating KRAS mutations, that have been reported in approximately 90% o...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1295936/full |
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| author | Daniele Lavacchi Simone Polvani Antonio Taddei Antonio Taddei Federico Scolari Luca Messerini Enrico Caliman Luca Moraldi Alessia Guidolin Gian Luca Grazi Andrea Galli Serena Pillozzi Lorenzo Antonuzzo Lorenzo Antonuzzo |
| author_facet | Daniele Lavacchi Simone Polvani Antonio Taddei Antonio Taddei Federico Scolari Luca Messerini Enrico Caliman Luca Moraldi Alessia Guidolin Gian Luca Grazi Andrea Galli Serena Pillozzi Lorenzo Antonuzzo Lorenzo Antonuzzo |
| author_sort | Daniele Lavacchi |
| collection | DOAJ |
| description | IntroductionPancreatic adenocarcinoma (PC) is one of the most lethal malignancies; even after resection the patients’ 5-year disease-free survival (DFS) is lower than 26%. The genetic mutational landscape of PC is dominated by activating KRAS mutations, that have been reported in approximately 90% of cases; however, beyond KRAS - direct mutations, several KRAS-targeting miRNAs appear to be downregulated, strengthening the already activated RAS signaling. In addition, the interplay between miRNAs and RAS includes poorly investigated downstream miRNAs. The aim of this study was to determine the prognostic value of some of these candidate KRAS-related miRNAs.Patients and methodsBetween 2015 and 2022, 44 patients with pathologically confirmed PC, who received surgery and were enrolled by the Clinical Oncology Unit, Careggi University Hospital, Florence (Italy). PC Total RNA was extracted from FFPE sections, retro-transcribed and the resulting cDNA was then used for qPCR analysis. A panel of KRAS-related miRNA (miR-155, miR-206 and miR-143) was analyzed.ResultsIn this observational study patients sex distribution was unequal with 34.1% being male and 65.9% female. The most frequent tumor localization was the head of the pancreas (65.9%) and the pathological stages were pT1-2 (45.5%), pT3 (54.5%), pN0 (22.7%), pN+ (77.3%). Adjuvant therapy was administered to 63.6% of patients; disease recurrence was observed in 69% of cases. Twenty-three patients, whose RNA was of adequate quality, were used in the mRNAs expression studies. When comparing the miRNA expression between PC and a pool of healthy tissues, miR-155 was overexpressed and miR-206 downregulated in PC, while miR-143 expression was unchanged. However, when categorized in low- and high- miR-143 expressing PC (according to the median value), high miR-143 was associated with nodal involvement (pN+) (p=0.029), who in turn was linked with shorter DFS (p=0.009) and overall survival (OS) (p=0.021) compared to pN0. A trend toward inferior DFS was observed for higher expression of miR-206 (p=0.095) and miR-143 (p=0.092). Finally, responders to a first-line treatment for advanced disease had miR-155 overexpressed (p=0.048).ConclusionsmiRNAs are involved in PC tumorigenesis and metastatic spread. In light of miR-143 association with lymphatic spread and poor prognosis, a comprehensive analysis of miRNA interplay with KRAS deserves further investigation. |
| first_indexed | 2024-03-09T02:56:35Z |
| format | Article |
| id | doaj.art-efcffb8b6c89433990e68a34e3066f61 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-09T02:56:35Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-efcffb8b6c89433990e68a34e3066f612023-12-05T04:35:54ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-12-011310.3389/fonc.2023.12959361295936KRAS-related miR-143 expression is associated with lymph node involvement and correlates with outcome in pancreatic adenocarcinoma patientsDaniele Lavacchi0Simone Polvani1Antonio Taddei2Antonio Taddei3Federico Scolari4Luca Messerini5Enrico Caliman6Luca Moraldi7Alessia Guidolin8Gian Luca Grazi9Andrea Galli10Serena Pillozzi11Lorenzo Antonuzzo12Lorenzo Antonuzzo13Clinical Oncology Unit, Careggi University Hospital, Florence, ItalyDepartment of Clinical and Experimental Biomedical Sciences “Mario Serio”, University of Florence, Florence, ItalyHPB Surgery Unit, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment of Health Sciences, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyClinical Oncology Unit, Careggi University Hospital, Florence, ItalyHPB Surgery Unit, Careggi University Hospital, Florence, ItalyClinical Oncology Unit, Careggi University Hospital, Florence, ItalyHPB Surgery Unit, Careggi University Hospital, Florence, ItalyDepartment of Clinical and Experimental Biomedical Sciences “Mario Serio”, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyClinical Oncology Unit, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyIntroductionPancreatic adenocarcinoma (PC) is one of the most lethal malignancies; even after resection the patients’ 5-year disease-free survival (DFS) is lower than 26%. The genetic mutational landscape of PC is dominated by activating KRAS mutations, that have been reported in approximately 90% of cases; however, beyond KRAS - direct mutations, several KRAS-targeting miRNAs appear to be downregulated, strengthening the already activated RAS signaling. In addition, the interplay between miRNAs and RAS includes poorly investigated downstream miRNAs. The aim of this study was to determine the prognostic value of some of these candidate KRAS-related miRNAs.Patients and methodsBetween 2015 and 2022, 44 patients with pathologically confirmed PC, who received surgery and were enrolled by the Clinical Oncology Unit, Careggi University Hospital, Florence (Italy). PC Total RNA was extracted from FFPE sections, retro-transcribed and the resulting cDNA was then used for qPCR analysis. A panel of KRAS-related miRNA (miR-155, miR-206 and miR-143) was analyzed.ResultsIn this observational study patients sex distribution was unequal with 34.1% being male and 65.9% female. The most frequent tumor localization was the head of the pancreas (65.9%) and the pathological stages were pT1-2 (45.5%), pT3 (54.5%), pN0 (22.7%), pN+ (77.3%). Adjuvant therapy was administered to 63.6% of patients; disease recurrence was observed in 69% of cases. Twenty-three patients, whose RNA was of adequate quality, were used in the mRNAs expression studies. When comparing the miRNA expression between PC and a pool of healthy tissues, miR-155 was overexpressed and miR-206 downregulated in PC, while miR-143 expression was unchanged. However, when categorized in low- and high- miR-143 expressing PC (according to the median value), high miR-143 was associated with nodal involvement (pN+) (p=0.029), who in turn was linked with shorter DFS (p=0.009) and overall survival (OS) (p=0.021) compared to pN0. A trend toward inferior DFS was observed for higher expression of miR-206 (p=0.095) and miR-143 (p=0.092). Finally, responders to a first-line treatment for advanced disease had miR-155 overexpressed (p=0.048).ConclusionsmiRNAs are involved in PC tumorigenesis and metastatic spread. In light of miR-143 association with lymphatic spread and poor prognosis, a comprehensive analysis of miRNA interplay with KRAS deserves further investigation.https://www.frontiersin.org/articles/10.3389/fonc.2023.1295936/fullpancreatic cancermiRNAKRASmiR-143miR-155miR-206 |
| spellingShingle | Daniele Lavacchi Simone Polvani Antonio Taddei Antonio Taddei Federico Scolari Luca Messerini Enrico Caliman Luca Moraldi Alessia Guidolin Gian Luca Grazi Andrea Galli Serena Pillozzi Lorenzo Antonuzzo Lorenzo Antonuzzo KRAS-related miR-143 expression is associated with lymph node involvement and correlates with outcome in pancreatic adenocarcinoma patients Frontiers in Oncology pancreatic cancer miRNA KRAS miR-143 miR-155 miR-206 |
| title | KRAS-related miR-143 expression is associated with lymph node involvement and correlates with outcome in pancreatic adenocarcinoma patients |
| title_full | KRAS-related miR-143 expression is associated with lymph node involvement and correlates with outcome in pancreatic adenocarcinoma patients |
| title_fullStr | KRAS-related miR-143 expression is associated with lymph node involvement and correlates with outcome in pancreatic adenocarcinoma patients |
| title_full_unstemmed | KRAS-related miR-143 expression is associated with lymph node involvement and correlates with outcome in pancreatic adenocarcinoma patients |
| title_short | KRAS-related miR-143 expression is associated with lymph node involvement and correlates with outcome in pancreatic adenocarcinoma patients |
| title_sort | kras related mir 143 expression is associated with lymph node involvement and correlates with outcome in pancreatic adenocarcinoma patients |
| topic | pancreatic cancer miRNA KRAS miR-143 miR-155 miR-206 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1295936/full |
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