TY - JOUR
T1 - Circulating miRNA Signature Predicts Cancer Incidence in Lynch Syndrome
T2 - A Pilot Study
AU - Sievänen, Tero
AU - Jokela, Tiina
AU - Hyvärinen, Matti
AU - Korhonen, Tia-Marje
AU - Pylvänäinen, Kirsi
AU - Mecklin, Jukka-Pekka
AU - Karvanen, Juha
AU - Sillanpää, Elina
AU - Seppälä, Toni T.
AU - Laakkonen, Eija K.
N1 - Publisher Copyright:
©2024 The Authors; Published by the American Association for Cancer Research.
PY - 2024/6/4
Y1 - 2024/6/4
N2 - Lynch syndrome (LS) is the most common autosomal dominant cancer syndrome and is characterized by high genetic cancer risk modified by lifestyle factors. This study explored whether a circulating miRNA (c-miR) signature predicts LS cancer incidence within a 4-year prospective surveillance period. To gain insight how lifestyle behavior could affect LS cancer risk, we investigated whether the cancer-predicting c-miR signature correlates with known risk-reducing factors such as physical activity, body mass index (BMI), dietary fiber, or NSAID usage. The study included 110 c-miR samples from LS carriers, 18 of whom were diagnosed with cancer during a 4-year prospective surveillance period. Lasso regression was utilized to find c-miRs associated with cancer risk. Individual risk sum derived from the chosen c-miRs was used to develop a model to predict LS cancer incidence. This model was validated using 5-fold cross-validation. Correlation and pathway analyses were applied to inspect biological functions of c-miRs. Pearson correlation was used to examine the associations of c-miR risk sum and lifestyle factors. hsa-miR-10b-5p, hsa-miR-125b-5p, hsa-miR-200a-3p, hsa-miR-3613-5p, and hsa-miR-3615 were identified as cancer predictors by Lasso, and their risk sum score associated with higher likelihood of cancer incidence (HR 2.72, 95% confidence interval: 1.64-4.52, C-index = 0.72). In cross-validation, the model indicated good concordance with the average C-index of 0.75 (0.6-1.0). Coregulated hsa-miR-10b-5p, hsa-miR-125b-5p, and hsa-miR-200a-3p targeted genes involved in cancer-associated biological pathways. The c-miR risk sum score correlated with BMI (r = 0.23, P < 0.01). In summary, BMI-associated c-miRs predict LS cancer incidence within 4 years, although further validation is required. PREVENTION RELEVANCE: The development of cancer risk prediction models is key to improving the survival of patients with LS. This pilot study describes a serum miRNA signature-based risk prediction model that predicts LS cancer incidence within 4 years, although further validation is required.
AB - Lynch syndrome (LS) is the most common autosomal dominant cancer syndrome and is characterized by high genetic cancer risk modified by lifestyle factors. This study explored whether a circulating miRNA (c-miR) signature predicts LS cancer incidence within a 4-year prospective surveillance period. To gain insight how lifestyle behavior could affect LS cancer risk, we investigated whether the cancer-predicting c-miR signature correlates with known risk-reducing factors such as physical activity, body mass index (BMI), dietary fiber, or NSAID usage. The study included 110 c-miR samples from LS carriers, 18 of whom were diagnosed with cancer during a 4-year prospective surveillance period. Lasso regression was utilized to find c-miRs associated with cancer risk. Individual risk sum derived from the chosen c-miRs was used to develop a model to predict LS cancer incidence. This model was validated using 5-fold cross-validation. Correlation and pathway analyses were applied to inspect biological functions of c-miRs. Pearson correlation was used to examine the associations of c-miR risk sum and lifestyle factors. hsa-miR-10b-5p, hsa-miR-125b-5p, hsa-miR-200a-3p, hsa-miR-3613-5p, and hsa-miR-3615 were identified as cancer predictors by Lasso, and their risk sum score associated with higher likelihood of cancer incidence (HR 2.72, 95% confidence interval: 1.64-4.52, C-index = 0.72). In cross-validation, the model indicated good concordance with the average C-index of 0.75 (0.6-1.0). Coregulated hsa-miR-10b-5p, hsa-miR-125b-5p, and hsa-miR-200a-3p targeted genes involved in cancer-associated biological pathways. The c-miR risk sum score correlated with BMI (r = 0.23, P < 0.01). In summary, BMI-associated c-miRs predict LS cancer incidence within 4 years, although further validation is required. PREVENTION RELEVANCE: The development of cancer risk prediction models is key to improving the survival of patients with LS. This pilot study describes a serum miRNA signature-based risk prediction model that predicts LS cancer incidence within 4 years, although further validation is required.
U2 - 10.1158/1940-6207.CAPR-23-0368
DO - 10.1158/1940-6207.CAPR-23-0368
M3 - Article
C2 - 38551987
AN - SCOPUS:85195226938
SN - 1940-6207
VL - 17
SP - 243
EP - 254
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 6
ER -
