Blood-Based Multiomics-Guided Detection of a Precancerous Pancreatic Tumor.

Over a decade ago, longitudinal multiomics analysis was pioneered for early disease detection and individually tailored precision health interventions. However, high sample processing costs, expansive multiomics measurements along with complex data analysis have made this approach to precision/personalized medicine impractical. Here we describe in a case report, a more practical approach that uses fewer measurements, annual sampling, and faster decision making. We also show how this approach offers promise to detect an exceedingly rare and potentially fatal condition before it fully manifests. Specifically, we describe in the present case report how longitudinal multiomics monitoring (LMOM) helped detect a precancerous pancreatic tumor and led to a successful surgical intervention. The patient, enrolled in an annual blood-based LMOM since 2018, had dramatic changes in the June 2021 and 2022 annual metabolomics and proteomics results that prompted further clinical diagnostic testing for pancreatic cancer. Using abdominal magnetic resonance imaging, a 2.6 cm lesion in the tail of the patient's pancreas was detected. The tumor fluid from an aspiration biopsy had 10,000 times that of normal carcinoembryonic antigen levels. After the tumor was surgically resected, histopathological findings confirmed it was a precancerous pancreatic tumor. Postoperative omics testing indicated that most metabolite and protein levels returned to patient's 2018 levels. This case report illustrates the potentials of blood LMOM for precision/personalized medicine, and new ways of thinking medical innovation for a potentially life-saving early diagnosis of pancreatic cancer. Blood LMOM warrants future programmatic translational research with the goals of precision medicine, and individually tailored cancer diagnoses and treatments.

Automatically transferring supervised targets method for segmenting lung lesion regions with CT imaging.

BACKGROUND: To present an approach that autonomously identifies and selects a self-selective optimal target for the purpose of enhancing learning efficiency to segment infected regions of the lung from chest computed tomography images. We designed a semi-supervised dual-branch framework for training, where the training set consisted of limited expert-annotated data and a large amount of coarsely annotated data that was automatically segmented based on Hu values, which were used to train both strong and weak branches. In addition, we employed the Lovasz scoring method to automatically switch the supervision target in the weak branch and select the optimal target as the supervision object for training. This method can use noisy labels for rapid localization during the early stages of training, and gradually use more accurate targets for supervised training as the training progresses. This approach can utilize a large number of samples that do not require manual annotation, and with the iterations of training, the supervised targets containing noise become closer and closer to the fine-annotated data, which significantly improves the accuracy of the final model. RESULTS: The proposed dual-branch deep learning network based on semi-supervision together with cost-effective samples achieved 83.56 ± 12.10 and 82.67 ± 8.04 on our internal and external test benchmarks measured by the mean Dice similarity coefficient (DSC). Through experimental comparison, the DSC value of the proposed algorithm was improved by 13.54% and 2.02% on the internal benchmark and 13.37% and 2.13% on the external benchmark compared with U-Net without extra sample assistance and the mean-teacher frontier algorithm, respectively. CONCLUSION: The cost-effective pseudolabeled samples assisted the training of DL models and achieved much better results compared with traditional DL models with manually labeled samples only. Furthermore, our method also achieved the best performance compared with other up-to-date dual branch structures.

Diversification of ranunculaceous petals in shape supports a generalized model for plant lateral organ morphogenesis and evolution.

Peltate organs, such as the prey-capturing traps of carnivorous plants and nectary-bearing petals of ranunculaceous species, are widespread in nature and have intrigued and perplexed scientists for centuries. Shifts in the expression domains of adaxial/abaxial genes have been shown to control leaf peltation in some carnivorous plants, yet the mechanisms underlying the generation of other peltate organs remain unclear. Here, we show that formation of various peltate ranunculaceous petals was also caused by shifts in the expression domains of adaxial/abaxial genes, followed by differentiated regional growth sculpting the margins and/or other parts of the organs. By inducing parameters to specify the time, position, and degree of the shifts and growth, we further propose a generalized modeling system, through which various unifacial, bifacial, and peltate organs can be simulated. These results demonstrate the existence of a hierarchical morphospace system and pave the way to understand the mechanisms underlying plant organ diversification.

T-SPOT with CT image analysis based on deep learning for early differential diagnosis of nontuberculous mycobacteria pulmonary disease and pulmonary tuberculosis.

OBJECTIVES: This study aimed to establish a diagnostic algorithm combining T-SPOT with computed tomography image analysis based on deep learning (DL) for early differential diagnosis of nontuberculous mycobacteria pulmonary disease (NTM-PD) and pulmonary tuberculosis (PTB). METHODS: A total of 1049 cases were enrolled, including 467 NTM-PD and 582 PTB cases. A total of 320 cases (160 NTM-PD and 160 PTB) were randomized as the testing set and were analyzed using T-SPOT combined with the DL model. The testing cases were first divided into T-SPOT-positive and -negative groups, and the DL model was then used to separate the cases into four subgroups further. RESULTS: The precision was found to be 91.7% for the subgroup of T-SPOT-negative and DL classified as NTM-PD, and 89.8% for T-SPOT-positive and DL classified as PTB, which covered 66.9% of the total cases, compared with the accuracy rate of 80.3% of T-SPOT alone. In the other two remaining groups, where the T-SPOT prediction was inconsistent with the DL model, the accuracy was 73.0% and 52.2%, separately. CONCLUSION: Our study shows that the new diagnostic system combining T-SPOT with DL based computed tomography image analysis can greatly improve the classification precision of NTM-PD and PTB when the two methods of prediction are consistent.

Disruption of enhancer-driven S100A14 expression promotes esophageal carcinogenesis.

Increasing evidence have revealed that epigenomic and genomic factors jointly contribute to the malignancy of esophageal squamous cell carcinoma (ESCC). However, little is known regarding how enhancers regulate tumor suppressors and drive the tumorigenesis of ESCC. Here, we characterized S100A14 as a tumor suppressor in ESCC and showed that S100A14 deficiency dramatically promoted 4-nitroquinoline-1-oxide (4NQO) -induced tumorigenesis of ESCC and shortened survival of mice. Intriguingly, we found that S100A14 expression was driven by enhancer, and disruption of enhancer decreased the S100A14 expression in ESCC. Mechanistic investigation showed that S100A14 deficiency triggered aberrant differentiated program. TP63, SOX2 and EP300 occupied the enhancer region of S100A14 gene locus and regulated the expression of S100A14. Consistently, S100A14 is downregulated in ESCC tissues compared with their corresponding adjacent normal tissues, and lower S100A14 expression predicts poorer overall survival. Collectively, disruption of enhancer-regulated S100A14 induces ESCC tumorigenesis and it acts as a critical driver of ESCC tumorigenesis.

LHX2 Enhances the Malignant Phenotype of Esophageal Squamous Cell Carcinoma by Upregulating the Expression of SERPINE2.

LHX2 dysregulations have been found to present in cancers, but the function of LHX2 in esophageal squamous cell carcinoma (ESCC) remains unknown. Here, we report that LHX2 was upregulated in ESCC tissues in comparison to the LHX2 levels in adjacent normal tissues. Loss- and gain-of-function experiments demonstrated that the knockdown of LHX2 markedly inhibited ESCC cells' proliferation, migration, invasion, tumor growth and metastasis, whereas the overexpression of LHX2 had the opposite effects. A mechanistic investigation revealed that LHX2 bound to the promoter of SERPINE2 gene and transcriptionally regulated the expression of SERPINE2. Collectively, LHX2 facilitates ESCC tumor progression, and it could be a potential therapeutic target for ESCC.

A transcriptional hub integrating gibberellin-brassinosteroid signals to promote seed germination in Arabidopsis.

Seed germination is regulated by multiple phytohormones, including gibberellins (GAs) and brassinosteroids (BRs); however, the molecular mechanism underlying GA and BR co-induced seed germination is not well elucidated. We demonstrated that BRs induce seed germination through promoting testa and endosperm rupture in Arabidopsis. BRs promote cell elongation, rather than cell division, at the hypocotyl-radicle transition region of the embryonic axis during endosperm rupture. Two key basic helix-loop-helix transcription factors in the BR signaling pathway, HBI1 and BEE2, are involved in the regulation of endosperm rupture. Expression of HBI1 and BEE2 was induced in response to BR and GA treatment. In addition, HBI1- or BEE2-overexpressing Arabidopsis plants are less sensitive to the BR biosynthesis inhibitor, brassinazole, and the GA biosynthesis inhibitor, paclobutrazol. HBI1 and BEE2 promote endosperm rupture and seed germination by directly regulating the GA-Stimulated Arabidopsis 6 (GASA6) gene. Expression of GASA6 was altered in Arabidopsis overexpressing HBI1, BEE2, or SRDX-repressor forms of the two transcription factors. In addition, HBI1 interacts with BEE2 to synergistically activate GASA6 expression. Our findings define a new role for GASA6 in GA and BR signaling and reveal a regulatory module that controls GA and BR co-induced seed germination in Arabidopsis.

A Deep Learning System to Screen Novel Coronavirus Disease 2019 Pneumonia.

The real-time reverse transcription-polymerase chain reaction (RT-PCR) detection of viral RNA from sputum or nasopharyngeal swab had a relatively low positive rate in the early stage of coronavirus disease 2019 (COVID-19). Meanwhile, the manifestations of COVID-19 as seen through computed tomography (CT) imaging show individual characteristics that differ from those of other types of viral pneumonia such as influenza-A viral pneumonia (IAVP). This study aimed to establish an early screening model to distinguish COVID-19 from IAVP and healthy cases through pulmonary CT images using deep learning techniques. A total of 618 CT samples were collected: 219 samples from 110 patients with COVID-19 (mean age 50 years; 63 (57.3%) male patients); 224 samples from 224 patients with IAVP (mean age 61 years; 156 (69.6%) male patients); and 175 samples from 175 healthy cases (mean age 39 years; 97 (55.4%) male patients). All CT samples were contributed from three COVID-19-designated hospitals in Zhejiang Province, China. First, the candidate infection regions were segmented out from the pulmonary CT image set using a 3D deep learning model. These separated images were then categorized into the COVID-19, IAVP, and irrelevant to infection (ITI) groups, together with the corresponding confidence scores, using a location-attention classification model. Finally, the infection type and overall confidence score for each CT case were calculated using the Noisy-OR Bayesian function. The experimental result of the benchmark dataset showed that the overall accuracy rate was 86.7% in terms of all the CT cases taken together. The deep learning models established in this study were effective for the early screening of COVID-19 patients and were demonstrated to be a promising supplementary diagnostic method for frontline clinical doctors.

A S100A14-CCL2/CXCL5 signaling axis drives breast cancer metastasis.

Rationale: Chemokines contribute to cancer metastasis and have long been regarded as attractive therapeutic targets for cancer. However, controversy exists about whether neutralizing chemokines by antibodies promotes or inhibits tumor metastasis, suggesting that the approach to directly target chemokines needs to be scrutinized. Methods: Transwell assay, mouse metastasis experiments and survival analysis were performed to determine the functional role of S100A14 in breast cancer. RNA-Seq, secreted proteomics, ChIP, Western blot, ELISA, transwell assay and neutralizing antibody experiments were employed to investigate the underlying mechanism of S100A14 in breast cancer metastasis. Immunohistochemistry and ELISA were performed to examine the expression and serum levels of S100A14, CCL2 and CXCL5, respectively. Results: Overexpression of S100A14 significantly enhanced migration, invasion and metastasis of breast cancer cells. In contrast, knockout of S100A14 exhibited the opposite effects. Mechanistic studies demonstrated that S100A14 promotes breast cancer metastasis by upregulating the expression and secretion of CCL2 and CXCL5 via NF-κB mediated transcription. The clinical sample analyses showed that S100A14 expression is strongly associated with CCL2/CXCL5 expression and high expression of these three proteins is correlated with worse clinical outcomes. Notably, the serum levels of S100A14, CCL2/CXCL5 have significant diagnostic value for discerning breast cancer patients from healthy individuals. Conclusions: S100A14 is significantly upregulated in breast cancer, it can promote breast cancer metastasis by increasing the expression and secretion of CCL2/CXCL5 via RAGE-NF-κB pathway. And S100A14 has the potential to serve as a serological marker for diagnosis of breast cancer. Collectively, we identify S100A14 as an upstream regulator of CCL2/CXCL5 signaling and a metastatic driver of breast cancer.

USP48 Sustains Chemoresistance and Metastasis in Ovarian Cancer.

BACKGROUND: Ubiquitin specific protease 48 (USP48) is a member of the deubiquitinating enzymes (DUBs) family. However, the function of USP48 in ovarian cancer remains unclear. OBJECTIVE: The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation. METHODS: After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells. The subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly increases responsiveness to CBP, and alleviates the metastasis in vivo. Meanwhile, USP48 deficiency results in the improved survival of mice. RESULTS: Finally, the analysis of clinical samples and the TCGA and Kaplan-Meier Plot database revealed that the high expression of USP48 in ovarian cancer patients is associated with poor survival and resistance to CBP therapy. CONCLUSION: In summary, USP48 may be a potential therapeutic target for ovarian cancer patients.

The R2R3-MYB transcription factor GhMYB1a regulates flavonol and anthocyanin accumulation in Gerbera hybrida.

Anthocyanins and flavonols have vital roles in flower coloration, plant development, and defense. Because anthocyanins and flavonols share the same subcellular localization and common biosynthetic substrates, these pathways may compete for substrates. However, the mechanism regulating this potential competition remains unclear. Here, we identified GhMYB1a, an R2R3-MYB transcription factor involved in the regulation of anthocyanin and flavonol accumulation in gerbera (Gerberahybrida). GhMYB1a shares high sequence similarity with that of other characterized regulators of flavonol biosynthesis. In addition, GhMYB1a is also phylogenetically grouped with these proteins. The overexpression of GhMYB1a in gerbera and tobacco (Nicotianatabacum) resulted in decreased anthocyanin accumulation and increased accumulation of flavonols by upregulating the structural genes involved in flavonol biosynthesis. We further found that GhMYB1a functions as a homodimer instead of interacting with basic helix-loop-helix cofactors. These results suggest that GhMYB1a is involved in regulating the anthocyanin and flavonol metabolic pathways through precise regulation of gene expression. The functional characterization of GhMYB1a provides insight into the biosynthesis and regulation of flavonols and anthocyanins.

Evolution of enzyme activity, heavy metals bioavailability and microbial community in different temperature stages of the co-bioevaporation process.

Laboratory investigations documented enzyme activity, heavy metals' bioavailability and the bacterial community during co-bioevaporation treatment of food waste and landfill leachate. The activities of dehydrogenase, protease, urease and phosphatase were sensitive to the changes in operating temperature inherent in co-bioevaporation. The maximum dehydrogenase activity was appeared at warming 30 °C. The maximum hydrolytic activity of the microorganisms on protein, urea and phosphorus-containing organic compounds appeared at warming 50 °C. The bacteria mainly gathered on the surface and in the pores of the sludge particles used as a bulking agent. Bacterial abundance reached its maximum at warming 50 °C. Firmicutes, Actinobacterica and Proteobacterica were the dominant bacterial phyla involved. Even though co-bioevaporation concentrated the heavy metals in the leachate, their bioavailability was substantially reduced during the process.

S100A10 silencing suppresses proliferation, migration and invasion of ovarian cancer cells and enhances sensitivity to carboplatin.

BACKGROUND: Ovarian cancer is the leading cause of gynecological cancer-related mortality. The novel oncogene S100A10 has been reported to be involved in cancer cell proliferation, invasion and metastasis. The role of S100A10 in ovarian cancer has not been well studied and the effect of S100A10 on chemotherapy remains unclear. The aims of the present study were to investigate the functional role of S100A10 in the progression and carboplatin sensitivity of ovarian cancer. METHODS: We examined the expression levels in tissues of S100A10 in 138 cases of ovarian cancer by IHC. To determine the functional roles of downregulated S100A10 in ovarian cancer, cell proliferation, colony formation, cell migration and invasion assays were performed. Chemoresistance was analyzed by apoptosis assay. A xenograft tumor model was established to confirm the role of S100A10 in carboplatin resistance in vivo. Using Western blot assays, we also explored the possible mechanisms of S100A10 in ovarian cancer. RESULTS: The results showed that increased expression of S100A10 was positively associated with carboplatin resistance (P < 0.001), tumor grade (P = 0.048) and a poorer prognosis (P = 0.0053). Functional analyses demonstrated that S100A10 suppression significantly suppressed ovarian cancer cell proliferation, colony formation, cell migration and invasion, remarkably increased carboplatin-induced apoptosis in SKOV3 and A2780 cells and inhibited tumor growth in vivo. Downregulation of S100A10 expression could inhibit cell proliferation and enhance ovarian cancer cell sensitivity to carboplatin, possibly involving the regulation of cleaved-Caspase3 and cleaved-PARP. CONCLUSIONS: Together, the results of the present study reveal that S100A10 expression can be used as a predictive marker for the prognosis of ovarian cancer and chemosensitivity to carboplatin.

USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance.

Ubiquitin­specific protease 39 (USP39), as one of the deubiquitinating enzymes (DUBs), exhibits aberrant an expression and has oncogenic functions in several types of cancer. However, the function and underlying molecular mechanisms of action of USP39 in ovarian cancer remain largely undetermined. The present study thus aimed to investigate whether USP39 is a promising tumor­associated gene and whether it could be a viable target for overcoming chemotherapeutic resistance in ovarian cancer. The present study identified that USP39 was highly expressed in ovarian cancer samples with carboplatin resistance. A series of functional assays revealed that the knockdown of USP39 in ES2 and SKOV3 cells significantly decreased cell proliferation, induced cell cycle arrest at the G2/M phase and impaired the cell colony formation ability. USP39 deficiency enhanced the carboplatin­induced apoptosis of the SKOV3 cells via the activation of poly­ADP ribose polymerase and caspase­3. USP39 knockdown led to the inhibition of cell migration and invasion. The opposite effects were observed when USP39 was overexpressed in the ES2 and SKOV3 cells. In vivo animal models revealed that the subcutaneous transplantation and intraperitoneal injection of USP39­overexpressing ES2 cells increased tumor burden with or without treatment with carboplatin. However, the knockdown of USP39 suppressed SKOV3 cell growth in vivo. Mechanistic analyses also demonstrated that USP39 induced the phosphorylation of extracellular signal­regulated kinase and AKT and increased the expression of epidermal growth factor receptor and cyclin B1. Collectively, the findings of this study suggest that USP39 may paly a vital role in regulating ovarian cancer malignant phenotypes and carboplatin resistance. Therefore, USP39 may prove to be a promising therapeutic target for patients with ovarian cancer.

Overexpression of S100A14 contributes to malignant progression and predicts poor prognosis of lung adenocarcinoma.

BACKGROUND: S100A14 is a member of the S100 calcium-binding protein family that exerts important phenotypic effects on cell proliferation, apoptosis, differentiation, and motility. However, the functional role and potential clinical significance of S100A14 in lung adenocarcinoma has not yet been clarified. METHODS: We analyzed genomic alterations of S100A14 using The Cancer Genome Atlas lung adenocarcinoma genomic dataset. S100A14 displayed significant copy number amplification in lung adenocarcinoma. We detected S100A14 expression in lung adenocarcinoma and analyzed the correlation between S100A14 expression and clinicopathological characteristics. RESULTS: Immunohistochemical analysis showed that S100A14 expression was obviously upregulated in lung adenocarcinoma tissues compared to matched normal counterparts. Statistical analysis revealed that S100A14 expression strongly correlated with poor differentiation, metastasis, stage, smoking, and EGFR mutation. Furthermore, our data indicated that S100A14 serum levels were higher in lung adenocarcinoma patients than healthy controls. Intriguingly, S100A14 serum levels were related to distant metastasis (P = 0.028). High S100A14 expression was significantly associated with overall (P = 0.0016) and post progression (P = 0.039) survival. In addition, we investigated the biological functions of S100A14 in lung adenocarcinoma cell lines. The results demonstrated that S100A14 promoted cell migration and invasion of SPCA1 and Glc-82 cells. CONCLUSIONS: S100A14 increases the motility of lung adenocarcinoma cells, and might be a diagnostic and prognostic serum biomarker and potential therapeutic target for lung adenocarcinoma.

S100A1 promotes cell proliferation and migration and is associated with lymph node metastasis in ovarian cancer.

S100A1 is a calcium-binding protein belonging to the family of S100 proteins, and is highly expressed in ovarian cancer. However, its role in ovarian cancer has not yet been fully elucidated. In this study, we examined S100A1 expression in ovarian cancer tissues and normal tissue controls and analyzed the correlation between S100A1 expression and clinicopathological parameters. We found that S100A1 expression was significantly upregulated in ovarian cancer tissues compared with fallopian and normal ovarian epithelium tissues and was significantly associated with lymph node metastasis and International Federation of Gynecology and Obstetrics (FIGO) stages and tumor grades. We then investigated the biological functions of S100A1 in ovarian cancer by cell proliferation, fluorescence-activated cell sorting (FACS), and migration and invasion assays. The results indicated that S100A1 enhanced the ovarian cancer cell proliferation and migration. Together, our findings demonstrated that S100A1 plays an important role in the malignancy of ovarian cancer, and serves as a useful marker for the detection of ovarian malignancy.

S100A7 promotes the migration, invasion and metastasis of human cervical cancer cells through epithelial-mesenchymal transition.

S100A7 is an EF-hand calcium-binding protein that has been suggested to be implicated in cell proliferation, migration, invasion and tumor metastasis. However, its role in cervical cancer has not yet been fully clarified. The present study used immunohistochemistry analysis of S100A7 in clinical specimens of cervical cancer to show that S100A7 expression was significantly upregulated in cervical cancer tissues compared with normal cervical tissues and S100A7 expression in high grade cervical intraepithelial neoplasm (CIN) was significantly higher than cervical cancer. Statistical analysis showed that S100A7 expression was associated with tumor grade (P <0.01) and lymph node metastasis (P <0.05). Functional studies showed that overexpression of S100A7 in cervical cancer cells promoted migration, invasion and metastasis of cervical cancer cells without influencing cell proliferation. Furthermore, S100A7 was found to be secreted into the conditioned media and extracellular S100A7 enhanced cell migration and invasion. Mechanistically, S100A7 bound to RAGE and activated ERK signaling pathway. And S100A7 enhanced cell mesenchymal properties and induced epithelial-mesenchymal transition. In summary, these data reveal a crucial role for S100A7 in regulating cell migration, invasion, metastasis and EMT of cervical cancer and suggest that targeting S100A7 may offer a new targeted strategy for cervical cancer.

Integrin α6 promotes esophageal cancer metastasis and is targeted by miR-92b.

Tumor invasion and metastasis is responsible for the poor prognosis of esophageal squamous cell carcinoma (ESCC); therefore, exploring the mechanisms by which malignant cells disseminate, spread and flourish in secondary sites, as well as translating the bench results to clinical practice are in urgent need. Previous reports showed that integrin α6 increases in ESCC specimens and its dysregulated spatial localization correlates positively with the unfavorable outcome of ESCC patients. Here, we clarify that integrin α6 promotes invasion and metastasis of ESCC cells In vitro and in vivo. Mechanistically, decreased integrin α6 attenuates motility of malignant cells partially through deactivating Akt pathway, which is essential for ESCC cells motility. Moreover, integrin α6 serves as a genuine target of miR-92b in suppressing ESCC motility. Our results for the first time describe that miR-92b/integrin α6/Akt axis controls the motility of ESCC, thereby providing a promising diagnosis or therapeutic option.

MicroRNA-182 drives colonization and macroscopic metastasis via targeting its suppressor SNAI1 in breast cancer.

Metastasis is a multi-step process. Tumor cells occur epithelial-mesenchymal transition (EMT) to start metastasis, then, they need to undergo a reverse progression of EMT, mesenchymal-epithelial transition (MET), to colonize and form macrometastases at distant organs to complete the whole process of metastasis. Although microRNAs (miRNAs) functions in EMT process are well established, their influence on colonization and macrometastases formation remains unclear. Here, we established an EMT model in MCF-10A cells with SNAI1 overexpression, and characterized some EMT-related microRNAs. We identified that miR-182, which was directly suppressed by SNAI1, could enable an epithelial-like state in breast cancer cells in vitro, and enhance colonization and macrometastases in vivo. Subsequent studies showed that miR-182 exerted its function through targeting its suppressor SNAI1. Moreover, higher expression level of miR-182 was detected in metastatic lymph nodes, compared with paired primary tumor tissues. In addition, the expression level of miR-182 was negatively correlated with that of SNAI1 in these clinical specimens. Taking together, our findings describe the role of miR-182 in colonization and macrometastases in breast cancer for the first time, and provide a promise for diagnosis or therapy of breast cancer metastasis.