Fibrinogen-to-Neutrophil Ratio as a New Predictor of Central Lymph Node Metastasis in Patients with Papillary Thyroid Cancer and Type 2 Diabetes Mellitus.

Background: Many patients have a higher risk of thyroid cancer if they have both papillary thyroid carcinoma (PTC) and Type 2 diabetes mellitus (T2DM). Meanwhile, the primary reason for local PTC recurrence is cervical lymph node metastasis. Therefore, the prognosis of patients affects how cervical lymph nodes are managed during surgery. Due to surgical complications such as laryngeal nerve palsy and hypocalcemia, it is still debatable whether to prevent central lymph node dissection (CLND). Predicting central lymph node metastasis (CLNM) is crucial to direct CLND. It is unclear how important the fibrinogen-to-neutrophil ratio (FNR) is in thyroid cancer, so we looked into how it might help patients with PTC and T2DM predict CLNM. Patients and methods: Wenzhou Medical University's First Affiliated Hospital provided us with 413 patients with PTC and T2DM, randomly divided into a training set (N = 292) and a validation set (N = 121). Univariate and multivariate logistic regression analyses were used to identify independent risk factors. After constructing a nomogram, the validity of the model was evaluated. Results: The maximum tumor diameter, high-density lipoprotein, thyroxine, triglyceride, lymphocyte, and FNR were all identified as independent risk factors by multivariate logistic regression analysis. The C index of the training set was 0.775, and the validation set was 0.654. Conclusion: In patients with PTC and T2DM, preoperative FNR was an independent risk factor for CLNM.

Washout DNA copy number analysis by low-coverage whole genome sequencing for assessment of thyroid FNAs.

Background: Papillary thyroid microcarcinoma (PTMC) is defined as a papillary carcinoma measuring ≤ 10 mm. The current management of PTMC has become more conservative; however, there are high-risk tumor features that can be revealed only postoperatively. For thyroid cancer, BRAF mutations and somatic copy number variation (CNV) are the most common genetic events. Molecular testing may contribute to clinical decision-making by molecular risk stratification, for example predicting lymph node (LN) metastasis. Here, we build a risk stratification model based on molecular profiling of thyroid fine needle aspiration (FNA) washout DNA (wDNA) for the differential diagnosis of thyroid nodules. Methods: Fifty-eight patients were recruited, FNA wDNA samples were analyzed using CNV profiling through low-coverage whole genome sequencing (LC-WGS) and BRAF mutation was analyzed using quantitative PCR. FNA pathology was reported as a Bethesda System for Reporting Thyroid Cytopathology (BSRTC) score. Ultrasound examination produced a Thyroid Imaging Reporting and Data System (TIRADS) score. Results: In total, 37 (63.8%) patients with a TIRADS score of 4A, 13 (22.4%) patients with a TIRADS score of 4B, and 8 (13.8%) patients with a TIRADS score of 4C were recruited after ultrasound examination. All patients underwent FNA with wDNA profiling. CNVs were identified in 17 (29.3%) patients. CNVs were frequent in patients with a BSRTC score of V or VI, including eight (47.1%) patients with a score of VI and five (29.4%) with a score of V, but not in patients with a score of III, II, or I (0%). BRAF mutation was not significantly correlated with BSRTC score. LN metastasis was found more frequently in CNV-positive (CNV+) than in CNV-negative (CNV-) patients (85.7% vs. 34.6%, odds ratio = 11.33, p = 0.002). In total, three molecular subtypes of thyroid nodules were identified in this study: 1) CNV+, 2) CNV- and BRAF positive (BRAF+), and 3) CNV- and BRAF negative (BRAF-). For the CNV+ subtype, 10 (83.3%) lesions with LN metastasis were found, including four (100%) small lesions (i.e. ≤ 5 mm). For the CNV- and BRAF+ nodules, LN metastases were detected in only seven (60.0%) larger tumors (i.e. > 5 mm). For CNV- and BRAF- tumors, LN metastasis was also frequently found in larger tumors only. Conclusions: It is feasible to identify high-risk LN metastasis thyroid cancer from FNA washout samples preoperatively using wDNA CNV profiling using LC-WGS.

Seven Genes Associated With Lymphatic Metastasis in Thyroid Cancer That Is Linked to Tumor Immune Cell Infiltration.

OBJECTIVE: Since there are few studies exploring genes associated with lymphatic metastasis of thyroid carcinoma (THCA), this study was conducted to explore genes associated with lymphatic metastasis of THCA and to investigate the relationship with immune infiltration. METHODS: Differentially expressed genes associated with THCA lymphatic metastasis were analyzed based on The Cancer Genome Atlas Program (TCGA) database; a protein-protein interaction(PPI)network was constructed to screen for pivotal genes. Based on the identified hub genes, their expression in THCA with and without lymphatic metastasis were determined. Functional enrichment analysis was performed. The correlation between the identified genes and immune cell infiltration was explored. LASSO logistic regression analysis was performed to determine the risk score of the most relevant gene constructs and multifactor COX regression analysis based on genes in the risk score formula. RESULTS: A total of 115 genes were differentially expressed in THCA with and without lymphatic metastasis, including 28 upregulated genes and 87 downregulated genes. The PPI network identified seven hub genes (EVA1A, TIMP1, SERPINA1, FAM20A, FN1, TNC, MXRA8); the expression of all seven genes was upregulated in the group with lymphatic metastasis; Immuno-infiltration analysis showed that all seven genes were significantly positively correlated with macrophage M1 and NK cells and negatively correlated with T-cell CD4+ and myeloid dendritic cells. LASSO logistic regression analysis identified the five most relevant genes (EVA1A, SERPINA1, FN1, TNC, MXRA8), and multi-factor COX regression analysis showed EVA1A, SERPINA1 and FN1 as independent prognostic factors. CONCLUSION: Seven genes were associated with lymphatic metastasis of THCA and with tumor immune cell infiltration.

Major Vault Protein (MVP) Associated With BRAF V600E Mutation Is an Immune Microenvironment-Related Biomarker Promoting the Progression of Papillary Thyroid Cancer via MAPK/ERK and PI3K/AKT Pathways.

Papillary thyroid cancer (PTC) is the most common malignancy of the endocrine system, with an increase in incidence frequency. Major vault protein (MVP) is the main structural protein of the vault complex that has already been investigated in specific cancers. Yet the underlying biological functions and molecular mechanisms of MVP in PTC still remain considerably uncharacterized. Comprehensive analyses are predicated on several public datasets and local RNA-Seq cohort. Clinically, we found that MVP was upregulated in human PTC than in non-cancerous thyroid tissue and was correlated with vital clinicopathological parameters in PTC patients. MVP expression was associated with BRAF V600E, RAS, TERT, and RET status, and it was correlated with worse progression-free survival in PTC patients. Functionally, enrichment analysis provided new clues for the close relationship between MVP with cancer-related signaling pathways and the immune microenvironment in PTC. In PTC with high MVP expression, we found CD8+ T cells, regulatory T cells, and follicular helper T cells have a higher infiltration level. Intriguingly, MVP expression was positively correlated with multiple distinct phases of the anti-cancer immunity cycle. MVP knockdown significantly suppressed cell viability and colony formation, and promoted apoptosis. In addition, downregulated MVP markedly inhibited the migration and invasion potential of PTC cells. The rescue experiments showed that MVP could reverse the level of cell survival and migration. Mechanistically, MVP exerts its oncogenic function in PTC cells through activating PI3K/AKT/mTOR and MAPK/ERK pathways. These results point out that MVP is a reliable biomarker related to the immune microenvironment and provide a basis for elucidating the oncogenic roles of MVP in PTC progression.

Revealing the selective mechanisms of inhibitors to PARP-1 and PARP-2 via multiple computational methods.

BACKGROUND: Research has shown that Poly-ADP-ribose polymerases 1 (PARP-1) is a potential therapeutic target in the clinical treatment of breast cancer. An increasing number of studies have focused on the development of highly selective inhibitors that target PARP-1 over PARP-2, its closest isoform, to mitigate potential side effects. However, due to the highly conserved and similar binding sites of PARP-1 and PARP-2, there is a huge challenge for the discovery and design of PARP-1 inhibitors. Recently, it was reported that a potent PARP-1 inhibitor named NMS-P118 exhibited greater selectivity to PARP-1 over PARP-2 compared with a previously reported drug (Niraparib). However, the mechanisms underlying the effect of this inhibitor remains unclear. METHODS: In the present study, classical molecular dynamics (MD) simulations and accelerated molecular dynamics (aMD) simulations combined with structural and energetic analysis were used to investigate the structural dynamics and selective mechanisms of PARP-1 and PARP-2 that are bound to NMS-P118 and Niraparib with distinct selectivity. RESULTS: The results from classical MD simulations indicated that the selectivity of inhibitors may be controlled by electrostatic interactions, which were mainly due to the residues of Gln-322, Ser-328, Glu-335, and Tyr-455 in helix αF. The energetic differences were corroborated by the results from aMD simulations. CONCLUSION: This study provides new insights about how inhibitors specifically bind to PARP-1 over PARP-2, which may help facilitate the design of highly selective PARP-1 inhibitors in the future.

miR-20a-directed regulation of BID is associated with the TRAIL sensitivity in colorectal cancer.

MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in cancer processes. Although miR-20a has been reported to be altered in a range of cancers, the role of miR-20a in colorectal cancer is not fully characterized, and the relationship between miR-20a dysregulation and the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity is not defined. In the present study, we demonstrated significant upregulation of miR-20a in the serum of colorectal cancer patients, tumor tissues and cell lines by quantitative RT-PCR analysis. Furthermore, we found that the TRAIL-induced apoptosis was associated with the expression level of miR-20a in colorectal cancer. The knockdown of miR-20a by inhibitors increased the antitumor effect of TRAIL via caspase-8 dependent pathway. BID, which is a pro-apoptotic member of the Bcl-2 family, was found to be directly regulated by miR-20a in SW480 cells. The knockdown of miR-20a inhibited the translocation of tBID to the mitochondria, which induced the mitochondrial pathway of apoptosis. Notably, we found that the knockdown of miR-20a also reversed the resistance of TRAIL in established TRAIL-resistant SW480 cells by tBID-mitochondria pathway. Therefore, our results suggest that miR-20a acts as a tumor promoter in colorectal cancer, and the understanding of the miR-20a might be a potential therapeutic target for colorectal cancer.

Mining, Validation, and Clinical Significance of Colorectal Cancer (CRC)-Associated lncRNAs.

BACKGROUND: Colorectal cancer (CRC) is one of the deadliest tumours, but its pathogenesis remains unclear. The involvement of differentially expressed long non-coding RNAs (lncRNAs) in CRC tumorigenesis makes them suitable tumour biomarkers. METHODS/FINDINGS: Here, we screened 150 cases of CRC and 85 cases of paracancerous tissues in the GEO database for differentially expressed lncRNAs. The levels of lncRNA candidates in 84 CRC and paracancerous tissue samples were validated by qRT-PCR and their clinical significance was analyzed. We identified 15 lncRNAs with differential expression in CRC tumours; among them, AK098081 was significantly up-regulated, whereas AK025209, BC040303, BC037331, AK026659, and CR749831 were down-regulated in CRC. In a receiver operating characteristic curve analysis, the area under the curve for the six lncRNAs was 0.914. High expression of AK098081 and low expression of BC040303, CR749831, and BC037331 indicated poor CRC differentiation. CRC patients with lymph node metastasis had lower expression of BC037331. In addition, the group with high AK098081 expression presented significantly lower overall survival and disease-free survival rates than the low-expression group, confirming AK098081 as an independent risk factor for CRC patients. CONCLUSION/SIGNIFICANCE: In conclusion, we have identified multiple CRC-associated lncRNAs from microarray expression profiles that can serve as novel biomarkers for the diagnosis and prognosis of CRC.

Downregulated pseudogene CTNNAP1 promote tumor growth in human cancer by downregulating its cognate gene CTNNA1 expression.

Accumulating evidence indicates that deregulation of cancer-associated pseudogene is involved in the pathogenesis of cancer. In the study, we demonstrated that pseudogene CTNNAP1, for the CTNNA1 gene, was dysregulated in colorectal cancer and the degree of dysregulation was remarkably associated with tumor node metastasis (TNM) stage (P<0.05). The mechanistic experiments revealed that pseudogene CTNNAP1 played a pivotal role in the regulation of its cognate gene CTNNA1 by competition for microRNA-141. Moreover, gain-of-function approaches showed that overexpression of CTNNAP1 or CTNNA1 significantly inhibited cell proliferation and tumor growth in vitro and in vivo by inducing G0/G1 cell cycle arrest. Our findings add a new regulatory circuit via competing endogenous RNA (ceRNA) cross-talk between pseudogene CTNNAP1 and its cognate gene CTNNA1, and provide new insights into potential diagnostic biomarker for monitoring human colorectal cancer.

The long noncoding RNA CASC2 functions as a competing endogenous RNA by sponging miR-18a in colorectal cancer.

Recent evidence highlights the crucial regulatory roles of long noncoding RNAs (lncRNA) in tumor biology. In colorectal cancer (CRC), the expression of several lncRNAs is dysregulated and play essential roles in CRC tumorigenesis. However, the potential biological roles and regulatory mechanisms of the novel human lncRNA, CASC2 (cancer susceptibility candidate 2), in tumor biology are poorly understood. In this study, CASC2 expression was significantly decreased in CRC tissues and CRC cell lines, and decreased expression was significantly more frequent in patients with advanced tumor-node-metastasis stage disease (TNM III and IV) (P = 0.028). Further functional experiments indicate that CASC2 could directly upregulate PIAS3 expression by functioning as a competing endogenous RNA (ceRNA) for miR-18a. This interactions leads to the de-repression of genes downstream of STAT3 and consequentially inhibition of CRC cell proliferation and tumor growth in vitro and in vivo by extending the G0/G1-S phase transition. Taken together, these observations suggest CASC2 as a ceRNA plays an important role in CRC pathogenesis and may serve as a potential target for cancer diagnosis and treatment.

Knockdown of miR-221 promotes the cisplatin-inducing apoptosis by targeting the BIM-Bax/Bak axis in breast cancer.

Accumulating evidence shows that microRNAs (miRNAs) have a critical role in the initiation and progression of types of human cancer, including breast cancer. Recent research indicated that miRNAs are also related with the chemotherapy on cancers. In this study, the expression of miR-221 in breast cancer (BC) patients' serum and cancer tissues was found to be significantly up-regulated. The results of in vitro MTT assay indicated that although the anti-miR-221 oligonucleotide alone did not influence the viability of BC cell lines markedly, it significantly promoted the cytotoxicity of cisplatin (DDP) to BC cells. Mechanistic studies demonstrated that the gene of BIM (Bcl-2 interacting mediator of cell death), a pro-apoptotic Bcl-2 family protein, was up-regulated by the knockdown of miR-221. We found that the synergetic effect of anti-miR-221 on increasing the sensitivity of MDA-MB-231 was BIM dependant. Furthermore, results of immunoprecipitation showed the up-regulated BIM directly combined with the Bax and Bak, leading to mitochondrial dysfunction. Our results suggest the anti-miR-221 could promote the cisplatin-inducing apoptosis by targeting the Bim-Bax/Bak axis in breast cancer.

Potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in papillary thyroid cancer.

BACKGROUND: The purpose of this study was to evaluate the potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in patients with papillary thyroid carcinoma (PTC). METHODS: A total of 619 patients with PTC who underwent total thyroidectomy with lymph node dissection were enrolled in this study. Univariable and multivariate analyses were used. RESULTS: Hashimoto's thyroiditis was present in 35.9% (222 of 619) of PTCs. Multivariate logistic regressions showed that BRAF(V600E) mutation, sex, extrathyroidal extension, and lymph node metastasis were independent factors for Hashimoto's thyroiditis. Female sex, more frequent extrathyroidal extension, and a higher incidence of lymph node metastasis were significantly associated with PTCs accompanied by BRAF(V600E) mutation without Hashimoto's thyroiditis compared with PTCs accompanied by BRAF(V600E) mutation with Hashimoto's thyroiditis. CONCLUSION: Hashimoto's thyroiditis was negatively associated with BRAF(V600E) mutation, extrathyroidal extension, and lymph node metastasis. In addition, Hashimoto's thyroiditis was related to less lymph node metastasis and extrathyroidal extension in PTCs with BRAF(V600E) mutation. Therefore, Hashimoto's thyroiditis is a potentially protective factor in PTC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1019-E1025, 2016.

IL-27 rs153109 polymorphism increases the risk of colorectal cancer in Chinese Han population.

IL-27, a new member of the IL-12 family, has been found to have antitumor effects in colorectal cancer (CRC); therefore, polymorphisms of this protein may modulate CRC carcinogenesis. So, we studied the association of single nucleotide polymorphisms of the IL-27 gene with the risk of CRC occurrence using a case-control using 600 CRC patients and matched healthy controls. The IL-27 rs153109 polymorphism was analyzed with polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. Data indicate that GG, GA, and combined A-variant genotypes (GG + GA) conferred significantly greater risk of CRC (P=0.034, 0.002, and 0.001, respectively), and that G alleles were associated with higher susceptibility to CRC (P=0.001). However, no correlation was found between the IL-27 rs153109 polymorphism and particular clinical features. In conclusion, our data demonstrated a clear association of IL-27 rs153109 polymorphism and the risk of CRC development.

cir-ITCH plays an inhibitory role in colorectal cancer by regulating the Wnt/ß-catenin pathway.

Noncoding RNAs (ncRNAs) are the dominant product of eukaryotic transcription. These products range from short microRNAs (miRNAs) to long intergenic noncoding RNAs (lincRNAs). Circular RNAs composed of exonic sequences represent an understudied form of ncRNA that was discovered more than 20 years ago. Using a TaqMan-based reverse transcriptase polymerase chain reaction assay, we analyzed the relationship between cir-ITCH expression and colorectal cancer (CRC) in a total of 45 CRCs and paired adjacent non-tumor tissue samples. We found that cir-ITCH expression was typically down-regulated in CRC compared to the peritumoral tissue. This result, as well as several follow-up experiments, showed that cir-ITCH could increase the level of ITCH, which is involved in the inhibition of the Wnt/ß-catenin pathway. Therefore, our results showed that cir-ITCH plays a role in CRC by regulating the Wnt/ß-catenin pathway.

Number of central lymph node metastasis for predicting lateral lymph node metastasis in papillary thyroid microcarcinoma.

BACKGROUND: The purpose of this study was to present our evaluation of the relationship between the number of positive central lymph nodes and lateral lymph node metastasis in patients with papillary thyroid microcarcinoma (PTMC). METHODS: Up to 141 patients with PTMC were divided into 3 groups according to different positive central lymph node classifications as follows: group A, no positive central lymph node; group B, 1 positive central lymph node; and group C, 2 or more positive central lymph nodes. RESULTS: Incidence of lateral lymph node metastasis was 30.5% (43 of 141). It was significantly high in group C compared with groups A and B, although there was no significant difference between groups A and B. Number of positive central lymph node ≥2, underlying Hashimoto thyroiditis, and extrathyroidal extension were the independent predictive factors for lateral lymph node metastasis on multivariate analysis. CONCLUSION: Lateral lymph node metastasis was mainly observed in patients with ≥2 positive central lymph nodes, which is an independent predictive factor for lateral lymph node metastasis. Therefore, ≥2 positive central lymph nodes may be valuable in predicting lateral lymph node metastasis.

Down-regulation of miRNA-30a in human plasma is a novel marker for breast cancer.

The present study was to evaluate the value of miRNA-30a in plasma as potential tumor marker in detecting breast cancer (BC). Using a novel approach to extract miRNA-30a from the plasma followed by real-time quantitative polymerase chain reaction (RQ-PCR) analysis, levels of miRNA-30a were quantified in plasma specimens of 100 BCs and 64 age-matched and disease-free healthy controls (HC). And we compared the diagnostic value of plasma miRNA-30a with conventional circulating tumor markers CA153 and CEA. The median levels of miRNA-30a were significantly lower in preoperative BC than those in HC (P < 0.001). The levels of CEA and CA153 were all significantly higher in preoperative BC compared with those in HC (P = 0.008 and P = 0.001, respectively), and only the level of CA153 decreased in postoperative BC compared with preoperative BC (P = 0.015). ROC analysis showed the sensitivity and specificity of miRNA-30a for BC diagnosis at 74.0 and 65.6 %, respectively, whereas the sensitivities of CEA and CA153 were 12.0 and 14.0 %, respectively. The status of ER and triple-negative BC was significantly associated with miRNA-30a level (P = 0.007 and P = 0.005, respectively). And no other clinicopathological features were found to had significant difference. Our findings suggest that plasma miRNA-30a decreased in patients with BC and has great potential to use as novel biomarkers for BC diagnosis.

Different distribution of breast ductal carcinoma in situ, ductal carcinoma in situ with microinvasion, and invasion breast cancer.

BACKGROUND: Breast ductal cancer in situ (DCIS) can recur or progress to invasive ductal cancer (IDC), and the interim stage include DCIS with microinvasion (DCIS-Mi). In this article, we attempt to study the study the differences of clinicopathological features, imaging data, and immunohistochemical-based subtypes among DCIS, DCIS-Mi, and IDC. METHODS: In this retrospective study, we attempt to compare the clinicopathological features, immunohistochemical results and imaging data of 866 patients (included 73 DCIS, 72 DCIS-Mi, and 721 IDC). RESULTS: Patients with DCIS and DCIS-Mi were younger than those with IDC (P = 0.007). DCIS and DCIS-Mi often happened in premenopausal women while IDC was opposite (P <0.001). The incidence of IDC with node-positive was significantly higher than it in DCIS and DCIS-Mi (P <0.001). We also observed that the Her2-positive was more often found in patients with pure DCIS compared to those with DCIS-Mi and DCIS-I (P <0.001). There was a significant difference between the four subgroups (Luminal-A, Luminal-B, ERBB2+, Basal-like) from DCIS, DCIS-Mi, and IDC (P <0.001). Basal-like patients were fewer than other subgroups in DCIS, DCIS-Mi, and IDC. The incidence of the first performance of ultrasound (catheter winded and nodular mass) and mammography (nodular mass) had significantly difference among patients with DCIS, DCIS-Mi, and IDC (P <0.001). CONCLUSIONS: Different clinicopathological, immunohistochemical, and imaging features among DCIS, DCIS-Mi, and IDC indicate that they are distinct entities. A larger sample size is needed for further study.

Predicting the factors of lateral lymph node metastasis in papillary microcarcinoma of the thyroid in eastern China.

INTRODUCTION: Lateral lymph node metastasis is common in papillary thyroid microcarcinoma (PTMC). The present study evaluated the clinicopathologic characteristics and ultrasonographic (US) findings in predicting lateral LNM from PTMC in eastern China. MATERIALS AND METHODS: A total of 176 patients with confirmed PTMC by final histological examination who underwent central lymph node dissection (LND) and lateral LND were enrolled in our study. The clinicopathological and US data from the cases were analyzed retrospectively to determine the independent predictive factors for lateral LNM. Then, a scoring system was developed on the basis of independent factors. The sum of the points for individuals was evaluated for the value in predicting lateral LNM. RESULTS: Central LNM, underlying Hashimoto's thyroiditis, upper pole location, no well-defined margin and presence of calcifications were independent predictive factors for lateral LNM on multivariate analysis. Clinicopathological and US index points were statistically significant, with ≤ 2 favoring lateral LNM negativity with a sensitivity of 83.3 %, positive predictive value of 89.6 % and negative predictive value of 72.9 %. CONCLUSIONS: When the evaluation for lateral lymph nodes from a preoperative approach is inadequate or not obvious, our scoring system for prediction of lateral LNM can be another choice. Patients with clinicopathological and US index points ≤ 2 could be considered as lateral LNM negative, so more diagnostic approach is recommended for patients with clinicopathological and US index points >2.

Clinical significance of miR-155 expression in breast cancer and effects of miR-155 ASO on cell viability and apoptosis.

Accumulating evidence shows that mircroRNAs (miRNAs) play a vital role in tumorigenesis. miR-155 is one of the most multifunctional miRNAs whose overexpression has been found to be associated with different types of cancer including breast cancer. To further determine the potential involvement of miR-155 in breast cancer, we evaluated the expression levels of miR-155 by real-time PCR and correlated the results with clinicopathological features. Matched non-tumor and tumor tissues of 42 infiltrating ductal carcinomas and 3 infiltrating lobular carcinomas were analyzed for miR-155 expression by real-time PCR. Further, we used an antisense technique to inhibit miR-155 expression in vitro. WST-8 test was performed to evaluate cell viability and apoptosis assay was used to investigate the effect of the miR-155 antisense oligonucleotide (miR-155 ASO) on HS578T cell death. The expression levels of miR-155 were significantly higher in tumor tissues than the levels in matched non-tumor tissues (P<0.001). Up-regulated miR-155 expression was associated with lymph node positivity (P=0.034), higher proliferation index (Ki-67 >10%) (P=0.019) and advanced breast cancer TNM clinical stage (P=0.002). Interestingly, we next found that miR-155 expression levels had close relations with ER status (P=0.041) and PR status (P=0.029). Transfection efficiency detected by flow cytometry was higher than 70%, the WST-8 test showed that viability of HS578T cells was greatly reduced after transfection with miR-155 ASO compared with the scramble (SCR) group or the liposome group. The Annexin V-FITC/PI assay also indicated that transfection with miR-155 ASO promoted apoptosis.