miR-194 as predictive biomarker of responsiveness to neoadjuvant chemoradiotherapy in patients with locally advanced rectal adenocarcinoma

D’Angelo, Edoardo; Zanon, Carlo; Sensi, Francesca; Fassan, Matteo; Scarpa, Marco; Pucciarelli, Salvatore; Nitti, Donato; Agostini, Marco

doi:10.1136/jclinpath-2017-204690

Cited by 28 publications

(26 citation statements)

References 33 publications

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“…A series of 62 patients with locally advanced CRCs (all Caucasian; M/F = 42/20; age 64.3 ± 9.2 years; cTNM Stage II/III = 5/57) subjected to preoperative chemoradiotherapy followed by surgery was considered. The treatment conditions were as described in refs 32,33. All patients received a total dose of at least 45 Gy to the whole pelvis at 1.8 Gy daily, five…”

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confidence: 99%

miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer

et al. 2020

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BACKGROUND: Metabolic reprogramming towards aerobic glycolysis in cancer supports unrestricted cell proliferation, survival and chemoresistance. The molecular bases of these processes are still undefined. Recent reports suggest crucial roles for microRNAs. Here, we provide new evidence of the implication of miR-27a in modulating colorectal cancer (CRC) metabolism and chemoresistance. METHODS: A survey of miR-27a expression profile in TCGA-COAD dataset revealed that miR-27a-overexpressing CRCs are enriched in gene signatures of mitochondrial dysfunction, deregulated oxidative phosphorylation, mTOR activation and reduced chemosensitivity. The same pathways were analysed in cell lines in which we modified miR-27a levels. The response to chemotherapy was investigated in an independent cohort and cell lines. RESULTS: miR-27a upregulation in vitro associated with impaired oxidative phosphorylation, overall mitochondrial activities and slight influence on glycolysis. miR-27a hampered AMPK, enhanced mTOR signalling and acted in concert with oncogenes and tumour cell metabolic regulators to force an aerobic glycolytic metabolism supporting biomass production, unrestricted growth and chemoresistance. This latter association was confirmed in our cohort of patients and cell lines. CONCLUSIONS: We disclose an unprecedented role for miR-27a as a master regulator of cancer metabolism reprogramming that impinges on CRC response to chemotherapy, underscoring its theragnostic properties.

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miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer

et al. 2020

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“…miRNA-194 has been described as a potential predictor of response to nCRT through a miRNA expression profiling approach combined with integrative computational biology [ 72 ]. miRNA-194 was highly expressed in endoscopic tumor biopsies collected before nCRT and before surgery that were analyzed by microarray, and then validated by RT-qPCR and in situ hybridization (ISH).…”

Section: Micrornas In Locally Advanced Rectal Cancermentioning

confidence: 99%

“…In addition, protein–protein interaction network and pathway enrichment analysis revealed that the molecular mechanism that triggers miR-194 overexpression involved the Wnt pathway via its downstream mediator tumor necrosis factor receptor-associated factor 6 (TRAF6). Moreover, the investigators suggested that the response to nCRT in which miR-194 overexpression is implicated, could be associated with the pathway of oxidative stress-induced senescence [ 72 ].…”

Section: Micrornas In Locally Advanced Rectal Cancermentioning

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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“…Yu et al carried out a global miRNA analysis in CRT‐sensitive and ‐resistant patients and found that miR‐345 was significantly elevated in CRT‐resistant patients ( P = 0.002) . Some other miRNAs, including miR‐194, ‐145, ‐21, ‐125b, and ‐143, have been reported to be the predictive biomarkers of CRT . None of them has been clinically assessed; however, it is possible that the optimal combination of these miRNAs can act as reliable biomarkers of a response to CRT.…”

Section: Future Of Ncrtmentioning

confidence: 99%

Recent advances of neoadjuvant chemoradiotherapy in rectal cancer: Future treatment perspectives

Yamashita

Matsuda

Hasegawa

et al. 2018

Annals of Gastroent Surgery

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Neoadjuvant chemoradiotherapy (nCRT) has been widely used as a multidisciplinary approach for stage II/III rectal cancer. However, its safety and efficacy are controversial because previous studies have shown conflicting outcomes. The present review aimed to elucidate the benefits and limitations of nCRT for patients with rectal cancer. Future perspectives of nCRT are also described. No recent randomized trials have been able to show a survival benefit, although many studies have demonstrated good local control with the use of fluoropyrimidine (e.g. 5‐fluorouracil [FU] or capecitabine)‐based nCRT. Addition of oxaliplatin (OX) to FU‐based nCRT might improve overall survival by preventing distant metastasis, as shown in recent meta‐analyses. However, control of adverse effects is an important concern with this treatment. New treatment strategies such as nonoperative management (watch and wait policy) and total neoadjuvant therapy (TNT) are promising, but the establishment of reliable diagnostic methods of metastasis is essential. Development of new biomarkers is also necessary to select patients who are more likely to benefit from nCRT.

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miR-194 as predictive biomarker of responsiveness to neoadjuvant chemoradiotherapy in patients with locally advanced rectal adenocarcinoma

Cited by 28 publications

References 33 publications

miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer

miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer

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

Recent advances of neoadjuvant chemoradiotherapy in rectal cancer: Future treatment perspectives

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