Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis

Ueda, Tetsuya; Volinia, Stefano; Okumura, Hiroshi; Shimizu, Masayoshi; Taccioli, Cristian; Rossi, Simona; Alder, Hansjüerg; Liu, Chang Gong; Oue, Naohide; Yasui, Wataru; Yoshida, Kazuhiro; Sasaki, Hiroki; Nomura, Sachiyo; Seto, Yasuyuki; Kaminishi, Michio; Calin, George A.; Croce, Carlo M.

doi:10.1016/s1470-2045(09)70343-2

Cited by 744 publications

(658 citation statements)

References 40 publications

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“…Interestingly, SGC-7901 and HGC-27 cell lines, which both originate from the lymph node metastatic locus of GC patients, had relatively lower miR-409-3p levels compared with other cell lines not originating from lymph node metastatic sites. Consistent with our results, an elegant microarray analysis 19 in GC tissues showed that miR-409-3p was associated with clinicopathological metastasis-related parameters such as peritoneal dissemination, depth of tumour invasion and lymph node metastasis. Recently, it was reported that miR-409 may be subjected to epigenetic modulation in GC, which in turn may be responsible for miR-409-3p downregulation in GC.…”

Section: Discussionsupporting

confidence: 91%

“…We focused on miR-409 to further explore the novel mechanism miRNAs have in advanced GC, because miR-409-3p is highly correlated to the metastatic status of GC patients. 19 However, the biological function of miR-409 in GC metastasis remains unknown.…”

Section: Introductionmentioning

confidence: 99%

“…RESULTS miR-409-3p is downregulated in GC and is associated with lymph node metastasis A previous microarray study has shown that miRNAs are differentially expressed in GC and that some miRNAs are correlated with the depth of invasion, lymph node metastasis and peritoneal metastasis; 19 however, the functional role of these miRNAs in the metastasis of GC remained unexplored. Cell migration and invasion have an important role in the process of cancer metastasis.…”

Section: Introductionmentioning

confidence: 99%

“…Overexpression of miR-409 suppresses distal pulmonary metastases and peritoneal dissemination in vivo miR-409-3p has been shown to be associated with the depth of invasion and peritoneal dissemination in GC patients, 19 so we examined the effects of miR-409 on distal pulmonary metastases and peritoneal dissemination in vivo. For pulmonary metastasis assays, SGC-7901 cells stably expressing miR-409 were injected into nude mice through the lateral tail vein.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

et al. 2011

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Emerging evidence has shown that aberrantly expressed microRNAs (miRNAs) are highly associated with tumour development and progression. However, little is known about the potential role of miRNAs in gastric cancer (GC) metastasis. In this study, miR-409-3p was found to be downregulated frequently in human GCs, and its expression was significantly associated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Enforced expression of miR-409 in GC cells significantly reduced their migration and invasion in vitro and their capacity to develop distal pulmonary metastases and peritoneal dissemination in vivo. Moreover, we found that miR-409 exerted its function predominantly through the mature miR-409-3p, but not miR-409-5p. Microarray and bioinformatics analysis identified the pro-metastatic gene radixin (RDX) as a potential miR-409-3p target. Further studies confirmed that miR-409-3p suppressed the expression of RDX by directly binding to its 3 0 -untranslated region. Silencing of RDX by small interfering RNAs phenocopied the effects of miR-409 overexpression, whereas restoration of RDX in miR-409-overexpressed GC cells reversed the suppressive effects of miR-409. Taken together, these results demonstrate that miR-409 suppresses GC cell invasion and metastasis by directly targeting RDX and that patients with downregulated miR-409-3p are prone to lymph node metastasis.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

et al. 2011

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“…Nevertheless, we are aware that such indirect comparisons might be further confounded by ethnic factors. Consistently, microRNA expression profiling and next-generation sequencing studies are beginning to unveil the existence of different sets of deregulated genes potentially associated with ethnicity, and differentiation type-related differences exist in dihydropyrimidine dehydrogenase levels [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Docetaxel, oxaliplatin, and capecitabine combination chemotherapy for metastatic gastric cancer

Lauro¹,

Vici²,

Belli³

et al. 2013

Gastric Cancer

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Background The incorporation of docetaxel into the cisplatin and fluorouracil backbone has been demonstrated to be an active combination in metastatic gastric cancer. Nevertheless, this regimen is burdened by nonnegligible toxicity. We hypothesized that replacing cisplatin and fluorouracil with oxaliplatin and capecitabine should be an active and safe option for metastatic gastric cancer patients. Methods In this phase II study, we tested the activity of docetaxel in combination with oxaliplatin and capecitabine (DOC) as a first-line treatment. DOC was administered as follows: docetaxel (60 mg/m 2 ) and oxaliplatin (100 mg/ m 2 ) on day 1, and capecitabine (500 mg/m 2 ) was administered orally twice daily given continuously, with cycles repeated every 3 weeks. The primary endpoint was the overall response rate. Results Forty-eight patients entered the study. All patients had metastatic disease (stage IV). None of the patients had previously received chemotherapy for advanced disease. Performance status was 0, 1, and 2 in 25, 58, and 17 % of patients, respectively; 13 patients (27 %) had adenocarcinoma of the gastroesophageal junction, and 29 patients (60.5 %) had two or more metastatic sites. The overall response rate was 52.1 %. Progression-free survival and overall survival were 6.9 and 12.6 months, respectively. The treatment was well tolerated with no treatmentrelated deaths. The most common grade 3-4 toxicity was neutropenia (41 %). Conclusions DOC is an effective and tolerated first-line treatment, and the lower dose of docetaxel and oxaliplatin used in this study compared with other similar regimens does not seem to hamper the antitumor activity.

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Genome‐wide identification of a novel miRNA‐based signature to predict recurrence in patients with gastric cancer

Yang

Zhao

et al. 2018

Molecular Oncology

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The current tumor node metastasis (TNM) staging system is inadequate for identifying high‐risk gastric cancer (GC) patients. Using a systematic and comprehensive‐biomarker discovery and validation approach, we attempted to build a microRNA (miRNA)‐recurrence classifier (MRC) to improve the prognostic prediction of GC. We identified 312 differentially expressed miRNAs in 446 GC tissues compared to 45 normal controls by analyzing high‐throughput data from The Cancer Genome Atlas (TCGA). Using a Cox regression model, we developed an 11‐miRNA signature that could successfully discriminate high‐risk patients in the training set (n = 372; P < 0.0001). Quantitative real‐time polymerase chain reaction‐based validation in an independent clinical cohort (n = 88) of formalin‐fixed paraffin‐embedded clinical GC samples showed that MRC‐derived high‐risk patients succumb to significantly poor recurrence‐free survival in GC patients (P < 0.0001). Cox and stratification analysis indicated that the prognostic value of this signature was independent of clinicopathological risk factors. Time‐dependent receiver operating characteristic (ROC) analysis revealed that the area under the curve of this signature was significantly larger than that of TNM stage in the TCGA (0.733 vs. 0.589 at 3 years, P = 0.004; 0.802 vs. 0.635 at 5 years, P = 0.005) and validation cohort (0.835 vs. 0.689 at 3 years, P = 0.003). A nomogram was constructed for clinical use, which integrated both MRC and clinical‐related variables (depth of invasion, lymph node status and distance metastasis) and did well in the calibration plots. In conclusion, this novel miRNA‐based signature is superior to currently used clinicopathological features for identifying high‐risk GC patients. It can be readily translated into clinical practice with formalin‐fixed paraffin‐embedded specimens for specific decision‐making applications.

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Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis

Cited by 744 publications

References 40 publications

MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

Docetaxel, oxaliplatin, and capecitabine combination chemotherapy for metastatic gastric cancer

Genome‐wide identification of a novel miRNA‐based signature to predict recurrence in patients with gastric cancer

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