Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients

Sclafani, Francesco; Chau, Ian; Cunningham, David; Lampis, Andrea; Hahne, Jens C.; Ghidini, Michele; Lote, Hazel; Zito, Domenico; Tabernero, Josep; Glimelius, Bengt; Begum, Ruwaida; Castro, David González de; Wilson, Sanna Hulkki; Peckitt, Clare; Eltahir, Zakaria; Wotherspoon, Andrew; Tait, Diana; Brown, Gina; Oates, J.; Braconi, Chiara; Valeri, Nicola

doi:10.1093/carcin/bgw073

Cited by 14 publications

(13 citation statements)

References 22 publications

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“…More and more studies have provided evidences to demonstrate that the SNPs in the miRNA genes, through impacting the interaction of miRNA with target genes and/or affecting the expression level of mature miRNA, result in dysregulation of target gene and consequent individual drug response and toxicity [ 9 ]. Several studies have shown that the miRNA-related SNPs are related to the efficacy and/or occurrence of adverse events of capecitabine-based chemotherapy for CRC patients [ 10 , 11 ]. For instance, Sclafani et al .…”

Section: Introductionmentioning

confidence: 99%

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The SNPs in pre-miRNA are related to the response of capecitabine-based therapy in advanced colon cancer patients

et al. 2017

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The single nucleotide polymorphisms (SNPs) in the microRNA precursor (pre-miRNA) may modulate the posttranscriptional regulation of gene expression and explain individual sensitivity to chemotherapy. Here we investigated the correlation between 23 SNPs in the pre-miRNA and the efficacy of capecitabine-based chemotherapy in 274 advanced colon cancer patients. Statistical analysis indicated that much more patients with rs744591 A/C(48.03%), C/C (53.45%) or C allele (49.73%) responded to the chemotherapy than those with the A/A genotype (33.71%). The response rates of rs745666 G/C heterozygous patients (35.25%) and C allele carriers (39.69%) were apparently less than that of the G/G homozygous patients (56.25%). Moreover, three SNPs rs2114358, rs35770269, and rs73239138 were significantly associated with the occurrence of side effects of chemotherapy. The patients with rs2114358 C allele (OR = 2.016) or rs35770269 T allele (OR = 2.299) were much more prone to endure adverse events. However, the incidence of side effect was lower in the patients carrying rs73239138 A allele than those with G/G genotype (OR = 0.500). Our findings demonstrate that genetic variations in pre-miRNA may influence the efficacy of capecitabine-based chemotherapy in advanced colon cancer patients.

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Section: Introductionmentioning

confidence: 99%

“…For instance, Sclafani et al . have shown that the rs4919510 CC genotype in miR-608 is associated with worse outcome in rectal cancer patients treated with neoadjuvant systemic chemotherapy followed by surgery and adjuvant chemotherapy [ 10 ]. Meulendijks et al .…”

Section: Introductionmentioning

confidence: 99%

The SNPs in pre-miRNA are related to the response of capecitabine-based therapy in advanced colon cancer patients

et al. 2017

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“…As consequence, a total of 35 SNPs were selected for genotyping. Although it has reported that some SNPs might affect chemotherapy efficacy in cancer patients, the evidence is not sufficient to address the role of these SNPs in survival, if only chemotherapy‐treated patients were included, unless these SNPs are also indeed involved in chemotherapy efficacy. Therefore, we first compared associations of the SNPs with survival between chemotherapy‐treated and untreated patients.…”

Section: Resultsmentioning

confidence: 99%

Functional genetic variants of XRCC4 and ERCC1 predict survival of gastric cancer patients treated with chemotherapy by regulating the gene expression

Cheng

Qiu

Wang

et al. 2017

Molecular Carcinogenesis

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DNA repair protects genomic integrity and may modulate chemotherapy efficacy. Few large-scale studies have evaluated predictive roles of genetic variants of DNA repair genes in survival of Chinese gastric cancer (GCa) patients treated with chemotherapy. Here, we assessed the roles of 35 single nucleotide polymorphisms (SNPs) in DNA repair genes in survival of 1002 GCa patients, of whom 694 received chemotherapy and 308 did not. Among patients receiving chemotherapy, the ERCC1 rs2298881A allele was associated with a better survival [hazards ratio (HR) = 0.82, 95% confidence interval (CI) = 0.69-0.98; P = 0.03], whereas two XRCC4 SNPs were associated with a worse survival (HR = 1.26, 95% CI = 1.03-1.54 for the rs10040363G allele, P = 0.02; and HR = 1.30, 95% CI = 1.06-1.59 for the rs2075685T allele, P = 0.01). These three SNPs were unique survival predictors for patients treated with chemotherapy (P < 0.05 for all) but not for patients without chemotherapy (P > 0.05 for all), suggesting that they modulated chemotherapy efficacy. Patients who received chemotherapy and had haplotypes with at least one death-risk allele in XRCC4 had a poor survival, and the trend for an increase in the number of death-risk alleles adversely affecting the survival was also observed in an allelic dose-dependent manner (P = 0.001). Further functional analysis revealed that the death-risk alleles up-regulated the gene expression, leading to a worse survival as suggested by our meta-analysis pooling both mRNA microarray data from the GEO database and published data (ERCC1: HR = 1.31 [1.08-1.58]; P = 0.006). These functional genetic variants may independently or jointly affect survival in chemotherapy-treated GCa patients by modulating the gene expression in the tumors.

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“…Few studies focused on the involvement of miR-SNPs in LARC [ 121 , 122 , 123 ]. For instance, the prognostic role of the SNP rs4919510, that is characterized by the guanine to cytosine (G > C) base substitution in the sequence of the mature miRNA-608, has been explored in LARC patients subjected to neodjuvant capecitabine and oxaliplatin (CAPOX) treatment followed by CRT, surgery, or to adjuvant CAPOX ± cetuximab treatment [ 121 ]. This retrospective study showed that the CC genotype was associated with a worse 5-year progression-free survival (PFS) in LARC patients treated with chemotherapy with respect to the CG/GG genotype patients.…”

Section: Single Nucleotide Polymorphisms (Snps) At Mirnas In Larcmentioning

confidence: 99%

“…This retrospective study showed that the CC genotype was associated with a worse 5-year progression-free survival (PFS) in LARC patients treated with chemotherapy with respect to the CG/GG genotype patients. Furthermore, the administration of cetuximab to the chemotherapy and CRT, significantly improves the 5-year PFS and OS in CC carriers when compared to CG/GG genotypes [ 121 ]. This study evidenced not only the role of miR-SNPs in the risk of cancer, but also their impact in drug response.…”

Section: Single Nucleotide Polymorphisms (Snps) At Mirnas In Larcmentioning

confidence: 99%

The Role of Micro-RNAs and Circulating Tumor Markers as Predictors of Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer

Palma

Luglio

Tropeano

et al. 2020

IJMS

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The response to neoadjuvant chemoradiation (nCRT) is a critical step in the management of locally advanced rectal cancer (LARC) patients. Only a minority of LARC patients responds completely to neoadjuvant treatments, thus avoiding invasive radical surgical resection. Moreover, toxic side effects can adversely affect patients’ survival. The difficulty in separating in advances responder from non-responder patients affected by LARC highlights the need for valid biomarkers that guide clinical decision-making. In this context, microRNAs (miRNAs) seem to be promising candidates for predicting LARC prognosis and/or therapy response, particularly due to their stability, facile detection, and disease-specific expression in human tissues, blood, serum, or urine. Although a considerable number of studies involving potential miRNA predictors to nCRT have been conducted over the years, to date, the identification of the perfect miRNA signatures or single miRNA, as well as their use in the clinical practice, is still representing a challenge for the management of LARC patients. In this review, we will first introduce LARC and its difficult management. Then, we will trace the scientific history and the key obstacles for the identification of specific miRNAs that predict responsiveness to nCRT. There is a high potential to identify non-invasive biomarkers that circulate in the human bloodstream and that might indicate the LARC patients who benefit from the watch-and-wait approach. For this, we will critically evaluate recent advances dealing with cell-free nucleic acids including miRNAs and circulating tumor cells as prognostic or predictive biomarkers.

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Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients

Abstract: SummaryAnalysis of a polymorphism in mature microRNA-608 (rs4919510) in rectal cancer patients enrolled in a randomized phase II clinical trial identified patient subpopulations who might benefit from the use of an intensified neo-adjuvant treatment strategy with Cetuximab.

Cited by 14 publications

References 22 publications

The SNPs in pre-miRNA are related to the response of capecitabine-based therapy in advanced colon cancer patients

The SNPs in pre-miRNA are related to the response of capecitabine-based therapy in advanced colon cancer patients

Functional genetic variants of XRCC4 and ERCC1 predict survival of gastric cancer patients treated with chemotherapy by regulating the gene expression

The Role of Micro-RNAs and Circulating Tumor Markers as Predictors of Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer

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