The value of the improved percutaneous and intravenous contrast-enhanced ultrasound diagnostic classification in sentinel lymph nodes of breast cancer.

Background: Metastatic burden of sentinel lymph node (SLN) in breast cancer patient is the basis for the decision to choose SLN biopsy or axillary lymph node dissection (ALND). However, the diagnostic performance of the previous percutaneous contrast-enhanced ultrasound (P-CEUS) and intravenous contrast-enhanced ultrasound (IV-CEUS) pattern were not satisfied. This study aimed to establish new classification based on structural characteristics for P-CEUS and IV-CEUS of SLN in breast cancer and evaluate the diagnostic efficacy. Methods: This retrospective study included consecutive breast cancer patients who had not received neoadjuvant therapy in the First Affiliated Hospital of Sun Yat-sen University between June 2019 and December 2021. Conventional ultrasound, P-CEUS and IV-CEUS were performed. The new classification methods for P-CEUS and IV-CEUS of SLN were established based on structural characteristics of SLN. Pathology was considered as the gold standard, the diagnostic efficacy of P-CEUS, IV-CEUS and combined contrast-enhanced ultrasound in SLNs was analyzed. Results: The detection rate of SLN by P-CEUS in 368 patients was 95.42%. The P-CEUS pattern of SLNs was divided into six types. The IV-CEUS sequence was divided into three types. The IV-CEUS mode was divided into four types. Among the 438 SLNs detected by P-CEUS, 105 (23.97%) were malignant and 333 (76.03%) were benign. Among the previously classified P-CEUS, P-CEUS, IV-CEUS and combined contrast-enhanced ultrasound, the latter had the highest diagnostic efficacy (P<0.05), with sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under curve (AUC) of 81.90% (86/105), 97.30% (324/333), 90.53% (86/95), 94.46% (324/343), 93.61% (410/438) and 0.896 (0.864-0.923), respectively. Conclusions: The new classification of the P-CEUS and IV-CEUS features of SLNs was performed based on structural characteristics of lymph nodes. Compared with the previously classified P-CEUS, the new classification method has higher diagnostic performance. The combination of new classified P-CEUS and IV-CEUS is helpful to further improve the diagnostic performance of SLNs.

Claudin18.2 expression and its clinicopathological feature in adenocarcinoma from various parts.

AIMS: To clarify claudin18.2 expression and its clinicopathological features in various cancers, especially in lung adenocarcinoma. METHODS: Immunohistochemistry staining and fluorescence in situ hybridisation (FISH) were performed to detect claudin18.2 expression and CLDN18 gene rearrangement in adenocarcinoma from different organs. RESULTS: The results showed that claudin18.2 expression was found in 68% (27 of 40) of lung mucinous adenocarcinoma, 52% (16 of 31) of cholangiocarcinoma, 2% (10 of 423) of colorectal adenocarcinoma tissue microarray, 27% (6 of 22) of colorectal mucinous adenocarcinoma and 30% (3 of 10) of cervical adenocarcinoma, but not in all 39 cases of invasive breast adenocarcinoma by immunohistochemistry staining. There was significantly positive correlation between ratio of claudin18.2-positive carcinoma cells and staining intensity in lung mucinous adenocarcinoma and cholangiocarcinoma. Claudin18.2 expression was much more in female patients than male patients with lung mucinous adenocarcinoma. In addition, cholangiocarcinoma with claudin18.2 expression was more aggressive and had perineural invasion. Intraductal papillary neoplasm of the bile duct and epithelial dysplasia of the adjacent bile in cholangiocarcinoma also showed claudin18.2 expression. All three cases of cervical adenocarcinoma with claudin18.2 expression were moderately differentiated adenocarcinoma including one human papillomavirus (HPV)-associated carcinoma, two non-HPV-associated and gastric-type carcinoma. CLDN18 gene rearrangement was not found in all 22 cases with high claudin18.2 expression by FISH. CONCLUSIONS: Our results suggest claudin18.2 might be a potential biomarker for targeted therapy on lung mucinous adenocarcinoma, cholangiocarcinoma, colorectal mucinous adenocarcinoma and gastric-type cervical adenocarcinoma.

Lnc NR2F1-AS1 Promotes Breast Cancer Metastasis by Targeting the MiR-25-3p/ZEB2 Axis.

Background: Long noncoding RNAs (lncRNAs) substantially affect tumor metastasis and are aberrantly expressed in various cancers. However, its role in breast cancer (BC) remains unclear. Methods: A microarray assay of differentially expressed lncRNAs in epithelial-mesenchymal transition (EMT) and non-EMT cells was performed. The prognostic value of lnc NR2F1-AS1 expression in patients with BC was analyzed using The Cancer Genome Atlas database. Lnc NR2F1-AS1 expression levels in different BC cell lines were assessed using quantitative real-time PCR. The role of lnc NR2F1-AS1 in BC cell metastasis was investigated in vitro and in vivo. Dual luciferase reporter assay and RNA immunoprecipitation were performed to investigate the relationship between lnc NR2F1-AS1, miR-25-3p, and ZEB2. Results: High levels of lnc NR2F1-AS1 were observed in BC cells undergoing EMT and were closely correlated with adverse prognosis in patients with BC. Lnc NR2F1-AS1 knockdown significantly inhibited BC cell migration, invasiveness in vitro, and metastasis in vivo. Mechanistically, lnc NR2F1-AS1 competitively binds to miR-25-3p to impede ZEB2 degradation, a positive EMT transcription factor in BC. Conclusions: Our study revealed a novel lnc NR2F1-AS1/miR-25-3p/ZEB2 axis in BC metastasis and that lnc NR2F1-AS1 may serve as a potential therapeutic target for BC metastasis.

Comparison of clinicopathological characteristics and response to neoadjuvant chemotherapy between HER2-low and HER2-zero breast cancer.

Novel anti-HER2 antibody-drug conjugates trastuzumab deruxtecan (DS-8201a) showed its effect in previously-treated HER2-low metastatic breast cancer, suggesting a promising future in HER2-low breast cancer. We retrospectively reviewed the clinicopathological data of 325 patients with stage I-III HER2 negative breast cancer who received neoadjuvant chemotherapy in the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2021. In general, 91 patients (28.0%) were HER2-zero, and 234 patients (72.0%) were HER2-low. The pathological complete response (pCR) rate of the entire cohort was 17.3%. The pCR rate was 16.7% in HER2-low group, and 18.9% in HER2-zero group, showing no significant difference. Patients with HER2-low tumors had significantly longer overall survival (OS) than patients with HER2-zero tumors. ER status was the affecting factor of OS in HER2-low patients in both univariate and multivariate analysis. In conclusion, evidence for HER2-low BC as a distinct entity is insufficient, and more efforts are needed to standardize the scoring of HER2-low breast cancer.

AI-Powered Segmentation of Invasive Carcinoma Regions in Breast Cancer Immunohistochemical Whole-Slide Images.

AIMS: The automation of quantitative evaluation for breast immunohistochemistry (IHC) plays a crucial role in reducing the workload of pathologists and enhancing the objectivity of diagnoses. However, current methods face challenges in achieving fully automated immunohistochemistry quantification due to the complexity of segmenting the tumor area into distinct ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) regions. Moreover, the quantitative analysis of immunohistochemistry requires a specific focus on invasive carcinoma regions. METHODS AND RESULTS: In this study, we propose an innovative approach to automatically identify invasive carcinoma regions in breast cancer immunohistochemistry whole-slide images (WSIs). Our method leverages a neural network that combines multi-scale morphological features with boundary features, enabling precise segmentation of invasive carcinoma regions without the need for additional H&E and P63 staining slides. In addition, we introduced an advanced semi-supervised learning algorithm, allowing efficient training of the model using unlabeled data. To evaluate the effectiveness of our approach, we constructed a dataset consisting of 618 IHC-stained WSIs from 170 cases, including four types of staining (ER, PR, HER2, and Ki-67). Notably, the model demonstrated an impressive intersection over union (IoU) score exceeding 80% on the test set. Furthermore, to ascertain the practical utility of our model in IHC quantitative evaluation, we constructed a fully automated Ki-67 scoring system based on the model's predictions. Comparative experiments convincingly demonstrated that our system exhibited high consistency with the scores given by experienced pathologists. CONCLUSIONS: Our developed model excels in accurately distinguishing between DCIS and invasive carcinoma regions in breast cancer immunohistochemistry WSIs. This method paves the way for a clinically available, fully automated immunohistochemistry quantitative scoring system.

The prognostic role of a phospho-Stathmin 1 signature in breast cancer treated with neoadjuvant chemotherapy.

Background: High expression of Stathmin 1 (STMN1) protein is related to a poor prognosis in various tumors, including breast cancer. In our previous study, a phospho-STMN1 signature was conducted to predict outcomes in adjuvantly treated breast cancer patients. This study aimed to explore the relationship of STMN1 expression with our phospho-STMN1 signature and the prognosis of patients treated with neoadjuvant chemotherapy (NACT). Methods: A retrospective analysis of 116 patients who received NACT in The First Affiliated Hospital of Sun Yat-sen University between December 2008 and March 2016 was conducted. Patients were followed up through telephone once a year until 2022. The levels of STMN1, Ser16, Ser25, Ser38, and Ser63 phosphorylation and GRP78 expression in pre-NACT biopsy specimens from the patients were detected by immunohistochemistry. The recurrence risk score for each patient was calculated using the p-STMN1/GRP78 model. Clinical and pathological parameters, pathological complete response and objective response rates, and survival data were analyzed. Results: In patients with NACT-treated breast cancer, high levels of STMN1, Ser25 phosphorylation, Ser38 phosphorylation, and GRP78 were related to worse disease-free survival (DFS), as was a high p-STMN1/GRP78 model risk score. In contrast, high Ser16 and Ser63 phosphorylation levels were related to better DFS [p-STMN1/GRP78 model: P=0.002, HR =0.180 (0.061-0.534); STMN1: P=0.001, HR =0.290 (0.147-0.572); Ser16: P=0.036, HR =2.019 (1.049-3.886); Ser25: P=0.013, HR =0.392 (0.188-0.819); Ser38: P=0.001, HR =0.293 (0.153-0.559); Ser63: P=0.006, HR =3.346 (1.407-7.961); GRP78: P=0.010, HR =0.417 (0.214-0.815)]. However, no significant statistical difference was found in the multivariate regression. The relationship between these markers and the therapeutic effect of NACT (pathological complete response and objective response) showed the same tendency with survival. The area under the receiver operating characteristic curve for the p-STMN1/GRP78 model was 0.790 (P=0.001) with sensitivity of 70% and specificity of 74%. Conclusions: The expression and serine phosphorylation status of STMN1 may be beneficial as biomarkers for predicting the prognosis of breast cancer patients treated with NACT. Our p-STMN1/GRP78 model could become a widely applied signature for assessing the metastatic risk of breast cancer patients, potentially facilitating their individualized management before NACT.

Retraction Notice to: hsa_circ_001653 Implicates in the Development of Pancreatic Ductal Adenocarcinoma by Regulating MicroRNA-377-MediatedHOXC6 Axis.

[This retracts the article DOI: 10.1016/j.omtn.2019.12.028.].

A clinicopathologic study of 13 cases of primary lymphoma in soft tissue and review of literature.

Primary lymphoma in soft tissue is very rare. In order to understand the clinicopathological features of primary lymphoma in soft tissue, we found 13 cases (0.3%) of primary lymphoma in soft tissue by reviewing 4303 lymphomas diagnosed in our institution from 2010 to 2019. Tumors were found in the following sites: 8 in lower extremity (2 in leg, 1 in calf, 1 in knee and 4 in buttock), 1 in upper extremity (left shoulder) and 4 in the trunk (3 in waist and 1 in thoracolumbar). The most common histologic type was DLBCL (7/13, 54.8%). 6 cases of which had follow-up information. 25 patients were also selected by screening the English literature search (from Jan 2010 to December 2019) including 1102 studies. Compared to the results of literature review, our results are similar with them. The tumor sites were as follows: 10 in lower extremity, 4 in upper extremity, 9 in the trunk and 2 in masticatory muscle. The most common histological type was also DLBCL (n=11/25, 44%). Overall survival analysis of all 31 patients including our 6 cases with primary lymphoma in soft tissue showed no significant difference between different histological type (Log Rank P=0.120, Breslow P=0.157). The differential diagnosis includes malignant melanoma, rhabdomyosarcoma and metastatic carcinoma in soft tissue.

Retraction Notice to: The Potential Therapeutic Role of Exosomal MicroRNA-520b Derived from Normal Fibroblasts in Pancreatic Cancer.

[This retracts the article DOI: 10.1016/j.omtn.2019.12.029.].

Clinicopathologic and molecular features of vascular tumors in a series of 118 cases.

AIMS: Vascular tumors are composed of benign, intermediate, and malignant lesions. The diagnosis is challenging because some entities demonstrate overlapping morphologies and harbor the same genetic alterations. We describe herein a cohort of vascular tumors with clinicopathologic, immunohistochemical, and molecular features. METHODS AND RESULTS: 118 vascular tumors including 56 angiosarcomas, 18 epithelioid haemangioendotheliomas (EHE), 25 epithelioid haemangiomas (EH), 8 pseudomyogenic haemangioendotheliomas (PHE), 1 papillary intralymphatic angioendothelioma (PILA), 2 kaposiform haemangioendotheliomas (KHE), 3 Kaposi sarcomas, 2 retiform haemangioendotheliomas (RHE), and 3 anastomosing haemangiomas were assessed. FOSB, c-Fos, CAMTA1, and TFE3 expression and gene rearrangements were analyzed by immunohistochemical staining and FISH, respectively. Our results showed that FOSB expression was diffusely positive in all 8 PHEs, focally or sparsely in 12 EHs, and in 2 angiosarcomas. C-FOS expression was sparsely to diffusely positive in 15 EHs, focally or sparsely in 17 angiosarcomas, 1 EHE, 1 Kaposi sarcoma, and 1 PHE. CAMTA1 expression was positive in only 12 EHEs. TFE3 expression was focally or sparsely positive in all 8 PHEs, 22 angiosarcomas, 6 EHEs, 3 EHs, 2 Kaposi sarcomas, and 2 AHs. FOSB rearrangement was found in 5 PHEs, FOS rearrangement only in 1 EH, CAMTA1 rearrangement in 4 EHEs. CONCLUSIONS: FOSB and CAMTA1 are useful diagnostic markers for PHE and EHE, respectively. FOSB and FOS fusion represent a subset of epithelioid haemangioma. TFE3 is not a diagnostically meaningful marker in a majority of vascular tumors. The combined utility of these markers will facilitate the differential diagnosis in vascular tumors with morphologic overlap.

Malignant adenomyoepithelioma of the breast: Two case reports and review of the literature.

BACKGROUND: Malignant adenomyoepithelioma (AME) of the breast is a rare tumor in which malignancy can arise from either epithelial or myoepithelial components, or from both cell types. The incidence and prognosis of malignant AME of the breast are difficult to assess due to its rarity. Therefore, the optimal treatment for this disease is still controversial. CASE SUMMARY: We present two middle-aged women (48 and 56 years old) with malignant AME of the breast. Core needle biopsy was performed before surgery. However, breast adenoma and malignant tumors were observed. The preoperative diagnosis of malignant AME of the breast is still challenging for pathologists and clinicians. Both patients underwent mastectomy and sentinel lymph node biopsy, both of which were negative, followed by adjuvant chemotherapy. CONCLUSION: The follow-up duration of the two patients was two years and four months, respectively. No signs of relapse or metastasis have been observed thus far.

A Prognosis Marker SLC2A3 Correlates With EMT and Immune Signature in Colorectal Cancer.

SLC2A3 is a membrane transporter that belongs to the solute carrier family, whose function includes transmembrane transport and glucose transmembrane transport activity. To clarify the expression and role of SLC2A3 in colorectal cancer (CRC), we analyzed the TCGA and GEO databases and found that SLC2A3 mRNA levels were significantly higher in CRC tissues than that in adjacent non-tumor tissues. Furthermore, high expression of SLC2A3 predicted poor overall survival and disease free survival for CRC patients. For validation, we collected 174 CRC samples and found that SLC2A3 expression was higher in CRC tissues than that in adjacent non-tumor colorectal mucosa tissues by immunohistochemistry staining. Further study showed that high expression of SLC2A3 was enriched in epithelial-mesenchymal transition (EMT) classical pathway, interferon-γ pathway by GSEA analysis enrichment, indicating that SLC2A3 may play a key role in the progression of CRC through EMT and immune response, which also has been validated by the global gene expression profiling of human CRC cell lines. The expression of SLC2A3 was positively correlated with CD4 and CD8+T cells by using TIMER and EPIC algorithm, respectively. SLC2A3 knockdown suppressed migration and inhibited the expression of Vimentin and MMP9 in CRC cell line SW480 and RKO. Meanwhile, PD-L1 expression was also significantly attenuated in SW480 and RKO cells transfected with SLC2A3 siRNA. The result suggests that SLC2A3 may be involved in the immune response of CRC by regulating PD-L1 immune checkpoint. In our series, SLC2A3 and PD-L1 positive expression was 74% (128/174) and 22% (39/174) of CRC, respectively. SLC2A3 expression was significantly associated with perineural invasion in CRC patients. In conclusion, SLC2A3 may play an important role in progression of CRC by regulating EMT and PD-L1 mediated immune responses.

Hemangioblastoma: clinicopathologic study of 42 cases with emphasis on TFE3 expression.

Hemangioblastomas (HBs) histologically overlap with TFE3 rearrangement-associated tumors, which present as alveolar architecture and clear or eosinophilic granular cytoplasm. However, whether TFE3 is expressed in HBs remains unexplored. Herein, we analyzed the clinicopathologic features of 42 HBs emphasizing studies of TFE3 expression. Of 42 cases, 38 were sporadic and 4 were regarded as a part of von Hippel-Lindau (VHL) syndrome according to clinical presentation. Nineteen patients were male and 23 were female. Patient age ranged from 17 to 70 years (median 43). Tumor size ranged from 0.4 to 4.8 cm (mean 2.2 cm). Follow-up ranged from 1 to 60 months and 6 patients developed recurrence. Immunohistochemistry staining showed that 36 (86%) of 42 HBs expressed TFE3 in nuclei of tumor cells, of which 21 were evaluated as high TFE3 expression levels. Increased TFE3 expression was significantly associated with older ages (P=0.018) and larger tumor size (P=0.001). Seventeen HBs with high TFE3 expression were negative for rearrangement and amplification of TFE3 by FISH analysis, 3 of which including 2 sporadic and 1 VHL-related HBs demonstrated trisomies or tetrasomies of X-chromosome in 7%~18% of tumor cells. All 3 cases occurred in female, presented with a larger tumor size and displayed a similar morphologic appearance with high cellularity and hyperchromatic nuclei. Our study first reports TFE3 expression and its clinicopathological relevance in HBs. We hypothesize that TFE3 might be involved in the pathogenesis of non-VHL-related HBs. Furthermore, HBs with strong TFE3 expression should be differentiated from brain-metastatic TFE3-rearranged tumors.

The Potential Therapeutic Role of Exosomal MicroRNA-520b Derived from Normal Fibroblasts in Pancreatic Cancer.

Pancreatic cancer (PC) remains a major health concern, with conventional cancer treatments exerting little influence on the disease course. MicroRNA-520b (miR-520b) functions as a tumor suppressor in several types of human cancers, whereas its anti-tumor property in the context of PC is still fundamental. The aim of this study is to identify the potential therapeutic role of miR-520b, transferred by exosomes, derived from normal fibroblasts (NFs) in PC progression. A gain-of-function study was performed to examine the roles of miR-520b in PC cell line SW1990, which suggested that miR-520b served as a tumor suppressor in PC. In order to confirm the role of exosomal miR-520b, exosomes were isolated from NF culture medium and cocultured with SW1990 cells. During the coculture experiments, we disrupted exosome secretion and upregulated exosomal miR-520b. The in vitro coculture studies revealed that miR-520b was transferred from NF-derived exosomes to PC cells and thereby suppressed PC cell proliferation, invasion, migration, and stimulated apoptosis. Furthermore, inhibited tumor growth and live metastasis upon elevated miR-520b in exosomes were observed in vivo. Conjointly, our study demonstrates that NF-derived exosomal miR-520b impedes the progression of PC, which contributes to a novel, therapeutic role of exosomal miR-520b for treating PC.

hsa_circ_001653 Implicates in the Development of Pancreatic Ductal Adenocarcinoma by Regulating MicroRNA-377-Mediated HOXC6 Axis.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive pancreatic cancer with poor survival rate. Circular RNAs (circRNAs) signatures have been identified in some human cancers, but there are little data concerning their presence in PDAC. We investigated the role of hsa_circ_001653, a newly identified circRNA, in the development of PDAC. hsa-circ-001653 expression was measured in 83 paired normal and tumor tissues surgically resected from PDAC patients. Phenotypic changes of PDAC cells were evaluated by assays for cell viability, cell cycle, invasion, and apoptosis. Tube-like structure formation of human umbilical vein endothelial cells (HUVECs) was examined in the presence of PDAC cells. Cross-talk between hsa_circ_001653 and microRNA-377 (miR-377)/human homeobox C6 (HOXC6) was assessed using dual-luciferase reporter assay, Ago2 immunoprecipitation, and northern blot analysis. Nude mice were inoculated with human PDAC cells for in vivo analysis. hsa_circ_001653 was an upregulated circRNA in PDAC. Silencing of hsa_circ_001653 in PDAC cells via RNA interference inhibited cell viability, cell-cycle progression, in vitro angiogenesis, and invasive properties, showing a pro-apoptotic effect. hsa_circ_001653 was found to bind to miR-377, which in turn repressed HOXC6 expression. Inhibition of miR-377 by its specific inhibitor restored cell viability, cell-cycle progression, in vitro angiogenesis, and invasive properties in PDAC cells lacking endogenous hsa_circ_001653. When nude mice were inoculated with human PDAC cells, inhibition of hsa_circ_001653 had a therapeutic effect. Collectively, the present study provides an enhanced understanding of hsa_circ_001653 as a therapeutic target for PDAC.

BCOR-CCNB3 fusion and BCOR internal tandem duplication in undifferentiated round cell sarcoma: a pathologic and molecular study of 5 cases.

Undifferentiated round cell sarcomas (URCSs) usually remained unclassified due to lack of known genetic abnormalities. Herein, we retrospectively collected 5 cases of URCSs and sought to investigate their unique clinicopathologic and molecular features for providing more accurate classification. There were 2 males and 3 females with age ranged from 7 months to 17 years. The tumors were respectively located in the sacrum, fibula, neck, perineum or groin. Microscopically, all 5 tumors were composed of small-to-medium sized cells with primitive morphology and variable cellularity, distributed within loose myxoid or collagenized fibroid stroma. These tumors lacked specific immunophenotypes and known gene rearrangements. However, the expression levels of CD99 and cyclin D1 were variable. RNA-sequencing data identified one BCOR-CCNB3 gene fusion-positive sarcoma occurring in the sacrum of a 17-year-old male patient. Whole genome sequencing analysis detected BCOR exon 15-internal tandem duplication (BCOR-ITD) in the tumor arising in the groin of one 7-month-old female infant. No specific gene abnormalities were found in the other 3 cases. Interestingly, a morphological and immunohistochemical overlap existed between BCOR-rearrangement tumor and BCOR-ITD-positive tumor, including areas with hypercellularity alternating with hypocellularity, a mixture of round cells and focal spindle cells, pale nuclear chromatin, inconspicuous nucleoli and abundant myxoid matrix, diffuse strong cyclin D1 expression, relatively strong expression of CD99 but lower than that in Ewing sarcoma, and a low Ki-67 proliferation index of about 10%. Our findings demonstrated a significant link between genetic aberration and histopathologic appearances, thus supporting the crucial role of genetic characteristics in accurate clinicopathological classification.

miR-338-3p suppresses colorectal cancer proliferation and progression by inhibiting MACC1.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. This study aimed to elucidate the clinicopathological significance of miR-338-3p and its association with metastasis-associated in colon cancer-1 (MACC1) in CRC. We evaluated miR-338-3p and MACC1 expression in CRC cell lines and analyzed the clinicopathological features of miR-338-3p in 98 samples of CRC tissues. Subsequent Western blot and cellular biological techniques, and xenograft mouse models were performed to investigate the biological role of miR-338-3p and its association with MACC1 in CRC. Our results show that miR-338-3p expression is lower in CRC cell lines and tissues than that in a human normal colonic epithelial cell line and adjacent normal colorectal tissue, respectively. miR-338-3p expression was significantly associated with histological differentiation, UICC stage, T classification, N classification, and M classification in 98 samples of CRC. The overall survival of CRC patients was significantly less in the low miR-338-3p expression group than in the high miR-338-3p expression group (p<0.01). miR-338-3p mimics suppressed cell proliferation, colony formation, migration, and invasion, but induced apoptosis in CRC cells. miR-338-3p inhibitor reversed these biological phenotypes. miR-338-3p mimics or inhibitor suppressed or increased MACC1 expression in HCT116 and SW620. miR-338-3p mimics reversed the effect of increased MACC1 expression induced by HCT116 with MACC1 over-expression plasmid. Increased cell proliferation, colony formation, and suppressed cell apoptosis caused by MACC1 over-expression were significantly reversed in HCT116 transfected with miR-338-3p mimics, respectively. Suppressed cell proliferation, colony formation, migration, invasion, and increased cell apoptosis caused by MACC1 knockdown were significantly reversed in SW620 transfected with miR-338-3p inhibitor, respectively. In vivo, miR-338-3p agomir significantly inhibited xenograft CRC tumor growth and reversed the effect of increased xenograft tumor growth induced from HCT116 with MACC1 overexpression. In conclusion, our data suggest that miR-338-3p suppresses CRC carcinogenesis and progression by inhibiting MACC1. Targeting miR-338-3p might be a novel treatment strategy for CRC.

The clinicopathological significance of ZNF10 in invasive ductal carcinoma of the breast.

The aim of this study was to clarify the clinicopathological features and role of zinc finger protein 10 (ZNF10) in breast invasive ductal cancer (IDC). Our data first showed that ZNF10 expression was higher in 8 pairs of fresh breast IDC and breast cancer cell lines compared with their respective adjacent non-tumor breast tissues. ZNF10 expression was significantly higher in IDC compared with DCIS and fibroadenoma of the breast. ZNF10 expression was significantly associated with patients' age, tumor stage, and breast cancer molecular subtype. ZNF10 knockdown inhibited breast cancer cell proliferation, colony formation, cell cycle progression, cell migration, and invasion but induced apoptosis. ZNF10 knockdown also suppressed the tumorigenicity of breast cancer in vivo. The underlying mechanism study showed that ZNF10 regulated the ß-catenin signaling pathway in breast cancer. ZNF10 might bind to the region (nucleotides -300 to +100) of the ß-catenin promoter. In conclusion, our results first suggest that ZNF10 promotes the carcinogenesis and progression of breast IDC via the ß-catenin signaling pathway. Targeting ZNF10 might be a novel treatment strategy for breast cancer.

miR-203a-3p promotes colorectal cancer proliferation and migration by targeting PDE4D.

Colorectal cancer (CRC) is a major worldwide health problem due to its high prevalence and mortality rate. microRNA has been reported playing an important role in a variety of cancers including colorectal cancer. miR-203a-3p has been found up-regulated in CRC tissues compare with the adjacent normal tissues. But, how miR-203a-3p regulates CRC development remains to be elucidated. In this study, gain and loss-of-function assays showed that miR-203a-3p promotes colorectal cancer cell proliferation, colony formation and migration and invasion by targeting PDE4D. And miR-203a-3p/ß-catenin/Cyclin D1/c-Myc signaling pathway is involved in the CRC. In summary, this study highlights an onco-miRNA role for miR-203a-3p by regulating PDE4D in CRC and suggests that miR-203a-3p may be a novel molecular therapeutic target for CRC.

GALNT6 suppresses progression of colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Invasion and metastasis are the main cause of mortality in most CRC patients. Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6) regulated glycosylation, which is frequently altered in cancers, and play an important role in cancer development. However, the role of GALNT6 in CRC remains unknown. To investigate the role of GALNT6 in CRC, first we studied correlation of GALNT6 expression levels with outcomes of CRC patients and found CRC patients with higher expression of GALNT6 had a better overall survival than those with lower expression. In addition, GALNT6 expression were significantly associated with tumor size, histological differentiation and lymph node metastasis. In vitro, GALNT6 overexpression dramatically inhibited cellular colony formation, migration, and invasion, and promoted the apoptosis of CRC cells. In vivo, CRC with GALNT6 overexpression showed reduced pulmonary metastasis in recipient mice compared with the controls. GALNT6 expression was significantly increased in SW480 and SW1116 cells cultured in hypoxic condition, and decreased in HT29 and LOVO cells with oxidative stress. Affimetrix microarray analysis showed that GALNT6 overexpression induced 279 genes up-regulated and 215 genes down-regulated in CRC. GALNT6 overexpression dramatically suppressed AKT and activated CD28 signaling pathway in CRC. AKT rescue experiment found that AKT was involved in GALNT6-induced CRC cell migration and invasion. In conclusion, our results first suggest that GALNT6 plays an important role in development and progression of CRC as a tumor suppressor gene.