The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: A classic and Bayesian meta-analysis

Ciliberto, Domenico; Staropoli, Nicoletta; Caglioti, Francesca; Chiellino, Silvia; Ierardi, Antonella; Ingargiola, Rossana; Botta, Cirino; Arbitrio, Mariamena; Correale, Pierpaolo; Tassone, Pierfrancesco; Tagliaferri, Pierosandro

doi:10.1016/j.critrevonc.2018.03.003

Cited by 18 publications

(21 citation statements)

References 62 publications

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“…Several interesting results from our study may promote further investigation into the functions and partners of miR-200s, push forward the clinical application of miR-200s and also provide us with more targets and strategies for therapy. Although not perfect, most of the findings from our results have been successfully confirmed by recent experimental literatures [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]. To better confirm the predictive power of our approach and understand the mechanisms underlying the initiation and progression of CRC, more large-scale and standard investigations are worth conducting.…”

Section: Discussionsupporting

confidence: 71%

“…The RAS signaling regulates cancer cell proliferation, apoptosis, inflammation, migration, and metastasis [42]. The aberrant RAS signaling may cause carcinogenesis and targeting it may bring substantial improvement in clinical outcome in metastatic colorectal cancers [43]. It is well established that mTOR signaling, a critical protein in regulating cancer cells, takes part in varieties of fundamental biological activities containing cell death, autophagy, metabolic reprogramming, cell growth, and cell cycle [44].…”

Section: Discussionmentioning

confidence: 99%

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Integrated characterization and validation of the prognostic significance of microRNA-200s in colorectal cancer

Peng

Cheng

et al. 2020

Cancer Cell Int

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Background: Accumulating evidence has demonstrated that could serve as promising molecular biomarkers for cancer prognosis. Nevertheless, the associations between miR-200s expression and colorectal cancer (CRC) prognosis remain controversial. Methods:We applied two mainstream approaches combining meta-analysis and bioinformatics analysis to answer whether miR-200s were associated with the prognosis of CRC patients and why miR-200s could be used as prognostic biomarkers for CRC. Results:Consequently, low expression of miR-200s was associated with unfavorable overall survival (OS) in CRC patients (HR: 1.09; 95% CI 1.01-1.17; P = 0.025). According to the subgroup analysis, the prognostic role of miR-200s was more significant for tissue samples, large samples, American patients and miR-200a subgroups. Then the target genes of miR-200s were predicted and applied for functional enrichment analyses. The results showed that the target genes of miR-200s were mainly enriched into some vital ontology subjects such as regulation ability, key cell structures and binding function. Moreover, a series of important signaling pathways were identified, which were significantly linked with the initiation and progression of CRC. Additionally, a protein-protein interaction (PPI) network of miR-200s targets was constructed to screen hub genes and modules. The identified hub genes and modules were validated to be highly involved in the occurrence and development of CRC.Conclusions: Current evidences revealed that miR-200s could be promising biomarkers for CRC prognosis. However, the findings still need to be validated with more larger-scale prospective studies and biological experiments before miR-200s could be applied into clinical application.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Integrated characterization and validation of the prognostic significance of microRNA-200s in colorectal cancer

Peng

Cheng

et al. 2020

Cancer Cell Int

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“…As performed in our previous works (Botta et al, 2017;Ciliberto et al, 2013Ciliberto et al, , 2012Ciliberto et al, 2018Ciliberto et al, , 2015Ciliberto et al, 2016;Staropoli et al, 2014Staropoli et al, , 2016, bibliographic research was conducted by PubMed, Embase, and the Central Registry of Controlled Trials of the Cochrane Library, major meeting proceeding databases (ASCO and ESMO). We identified a time frame comprises between January 2008, year of introduction of PARPis in clinical trials, and April 2018.…”

Section: Searchingmentioning

confidence: 99%

The Era of PARP inhibitors in ovarian cancer: “Class Action” or not? A systematic review and meta-analysis

Staropoli

Ciliberto

Giudice

et al. 2018

Critical Reviews in Oncology/Hematology

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Introduction: Carboplatin is the milestone of epithelial ovarian cancer (EOC) treatment, thus response to platinum is the major prognostic factor. Among platinum-sensitive patients, 40% carry a germline or somatic BRCA1/2 mutation. In this scenario a new class of drugs, the PARP inhibitors (PARPis), produced a significant improvement in long-term disease control. In order to make an aggregate evaluation of the impact of these agents, we performed a systematic review and meta-analysis. Patients and Methods: Clinical trials were selected by searching "Pubmed" database and abstracts from major cancer meetings. We considered the January 2008-April 2018 time frame. Progression free survival (PFS) was the primary end-point, toxicities were secondary end-points. Hazard ratios (HRs) of PFS, with confidence intervals, and risk ratios of grade 3-4 toxicity rates, were extracted from retrieved studies and included in the current analysis. Meta-analysis was carried out by the fixed and random effect models. We conducted this metaanalysis to also compare indirectly the efficacy of different PARPis in EOC patients. Results: Five randomized trials for a total of 1839 patients were selected and included in the final analysis. In particular, we evaluated a BRCA-mutant cohort (871 patients) with a pooled HR 0.25 (95%CI 0.21-0.31) and the BRCA-wild type cohort (836 patients) with a pooled HR 0.41 (95%CI 0.31-0.55), respectively. Regarding safety profile, no significant differences were detected in all grade toxicities, however, taking into account 3-4 grade toxicities and SAEs (severe adverse events), we show that rucaparib-treated patients reported major abdominal pain events, while niraparib-treated patients were associated with the highest percentage of haematological toxicities, hypothesizing a drug effect for the safety analysis. In the indirect comparisons, significant differences were not detected on PFS for the different agents. Conclusions: We confirm a significant benefit in survival outcome of PARPis for EOC patients with a "class effect" on the bases of narrow CI and indirect comparisons in the different groups. Therefore, we underline that this strategy is of special value in BRCA-mutated patients because genetic testing allows best patient selection for all PARPis with the added value of individualized prevention in familiars. 1. Background Among epithelial ovarian cancer (EOC) patients, women with genetic predisposition show an early onset of disease. Rare high penetrant mutations in BRCA1 and BRCA2 genes greatly increase lifetime risk and account for the majority of hereditary cases, 10%-15% of all cases. These women have a 40-60% lifetime risk of EOC (44% in BRCA1 families and 27% in BRCA2 families, respectively) (Mavaddat et al., 2012; Xu et al., 2017). The gold standard first-line treatment is still based on the combination of carboplatin/paclitaxel (du Bois et al., 1997; Jayson et al., 2014). The management of recurrent disease strictly depends on

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“…RAS is a fundamental protein in colon cancer [16][17][18]. Silencing CNN2 downregulated expression levels of K-ras and cyclin D1 proteins.…”

Section: Ras Signal Pathways Are Also Activated By Regulated Cnn1 Andmentioning

confidence: 99%

MicroRNA silencing of CNN1 and CNN2 protein family members regulates biology processes in colorectal cancer by targeting the p53 signal pathway

Huang

Wei

Wang

et al. 2020

Preprint

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BackgroundCalponin was first defined as a striated muscle troponin T-like protein that binds actin thin filaments to regulate smooth muscle contraction. There are few studies of CNN1 and CNN2 in colorectal cancer, and the roles these two genes play in colorectal cancer cell lines and the mechanisms by which they act are unknown.MethodsWe used immunohistochemistry to identify expression of the two genes in the cancer tissues. RT-PCR was used to measure expression levels of microRNA. W performed western blots to measure changes in signaling pathways in the context of expression interference.Meanwhile, the same method was used to measure binding relationship between the two genes and key pathway proteins. To determine the relationship between microRNA and gene mRNA, we used the reporter gene method. We used the chi-square and t-test methods to analyze the significance and correlations of the data.Results and conclusionsExpression levels of CNN1 were lower in colon cancer tissues than in normal mucosal tissues. After downregulating CNN1, the cell cycle in colon cancer cell lines progressed quickly, and the expression of related pathway proteins also increased. Expression levels of CNN2 were higher in colon cancer tissues, and its downregulation significantly inhibited cell cycle progression in colon cancer cell lines. We confirmed correlations between the expression of microRNA and CNN2 using data analysis.Bars indicate ± standard errors.*p < 0.05; **p < 0.01 compared with the control. The inhibition of the expression of CNN2 mRNA using microRNA was confirmed using western blot. The combination of the two at the mechanism level was also demonstrated using the reporter gene method.

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The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: A classic and Bayesian meta-analysis

Cited by 18 publications

References 62 publications

Integrated characterization and validation of the prognostic significance of microRNA-200s in colorectal cancer

Integrated characterization and validation of the prognostic significance of microRNA-200s in colorectal cancer

The Era of PARP inhibitors in ovarian cancer: “Class Action” or not? A systematic review and meta-analysis

MicroRNA silencing of CNN1 and CNN2 protein family members regulates biology processes in colorectal cancer by targeting the p53 signal pathway

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