Prognostic value and therapeutic potential of NEK family in stomach adenocarcinoma.

Never in mitosis gene A-related kinase (NEK) is an 11-membered family of serine/threonine kinases (NEK1-NEK11), which are known to play important roles in the formation and development of cancer. However, few studies have examined the roles of these kinases in the development of stomach adenocarcinoma (STAD). In this study, we conducted a comprehensive analysis of the relationships between the NEKs family members and STAD. The differential expression of the NEK genes in STAD was validated using The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER) databases, and their prognostic and diagnostic values of NEKs in STAD were assessed using the Kaplan-Meier plotter and TCGA data. The effect of NEK expression on immune cell infiltration in STAD was analysed using the TIMER and TISIDB databases. The expression levels of the majority of the NEK family members were consistently upregulated in STAD, whereas that of NEK10 was downregulated. The upregulation of NEK2/3/4/5/6/8 was closely associated with clinicopathological parameters of patients, and the overexpressed levels of these proteins had good diagnostic value for the disease. NEK1/8/9/10/11 expression correlated with poor overall survival and post-progressive survival, whereas a higher NEK1/6/9/11 level implied worse first progressive survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the NEKs may be related to immunological responses. Additionally, our study confirmed that these kinases correlated with immune cell infiltration and different immune infiltration subtypes in STAD. Our results suggest that NEK9 in particular has the potential to be used as a diagnostic and prognostic biomarker of STAD development and progression and an immune target for treatment of the disease. These findings expand our understanding of the biological functions of the NEK family members in STAD.

NKX2-1-AS1 promotes the lymphangiogenesis of lung adenocarcinoma through regulation of ERG-mediated FABP4.

Lymphatic metastasis is a common metastasis of lung adenocarcinoma (LUAD). The current study illustrated the action of lncRNA NKX2-1-AS1 in lymphangiogenesis in LUAD and the underlying mechanisms. Clinical tissue samples were collected for determining NKX2-1-AS1 expression. Then, H441 and H661 cells were selected to perform gain- and loss-of-function assays for dissecting the roles of NKX2-1-AS1 in LUAD cell proliferation and migration. Besides, H441 and H661 cell supernatant was harvested to stimulate HLECs for assessing tube formation ability. Interaction among NKX2-1-AS1, ERG, and fatty acid binding protein 4 (FABP4) was validated through luciferase and RIP assays. NKX2-1-AS1 was highly-expressed in LUAD tissues. Silencing NKX2-1-AS1 suppressed H441 and H661 cell proliferation and migration, reduced expression levels of lymphangiogenesis-related factors (LYVE-1, VEGF-C, VEGFR3, VEGF-A, VEGFR2, and CCR7), and inhibited HLEC tube formation. Interaction validation demonstrated that NKX2-1-AS1 regulated FABP4 transcription by binding to ERG. Overexpression of FABP4 could effectively block the inhibition role of NKX2-1-AS1 silencing in lymphangiogenesis in H441 and H661 cells. This study provided evidence that NKX2-1-AS1 regulated FABP4 transcription by binding to ERG to facilitate the proliferation and migration of LUAD cells and tube formation of HLECs, thus participating in lymphangiogenesis.

Malignant rhabdoid tumor of the omentum in an adult male: a case report and literature review.

Malignant rhabdoid tumors (MRTs) are rare tumors with high mortality rates and poor prognoses. MRTs occur mainly in the central nervous system, kidneys, and soft tissues, but rarely in the omentum. MRTs occur more commonly in infants and children and less frequently in adults. Here, we report the first observed case of MRT in an adult omentum. A 35-year-old man with abdominal distension and pain was admitted to the emergency department. Previously, several hospitals considered patients with cirrhosis who had not received active treatment. Computed tomography and magnetic resonance imaging revealed diffuse omental thickening and massive ascites. The surgery was performed at our hospital, and the pathological diagnosis was MRT with a SMARCB1(INI-1) deletion. Postoperatively, his symptoms improved, and he underwent five cycles of chemotherapy. However, 6 months after surgery, the tumor developed liver metastases, and the patient subsequently died. Primary MRT of the greater omentum is rare, and its pathological diagnosis usually requires extensive clinicopathological evaluation of various differential diagnoses and an appropriate work-up to exclude other malignancies associated with SMARCB1 deletion. At the same time, the lack of specific signs of omental MRT and its rapid progression should alert clinicians.

Purified Vitexin Compound 1 Serves as a Promising Antineoplastic Agent in Ovarian Cancer.

Ovarian cancer is a common gynecologic aggressive neoplasm. The mortality of ovarian cancer is top among gynecologic malignancies due to the insidious onset, atypical early symptoms, and chemoresistance. Therefore, it is urgent to seek another promising treatment for ovarian cancer. Purified vitexin compound 1 (VB1) is a kind of neolignan from the seed of traditional Chinese herb vitex negundo that possessed diverse pharmacological effects. VB1 can exhibit anti-neoplastic activities against various cancers. However, the role of VB1 in ovarian cancer treatment has not been elaborated, and the mechanism is unknown. The aim of this study was to investigate the therapeutic effects of VB1 in ovarian cancer cells both in vitro and in vivo, along with the molecular mechanism of action. In vitro, VB-1 can effectively suppress the proliferation, induce apoptosis, and block cell cycle at G2/M phase with a concentration dependent manner in ovarian cancer cells. Western blot assay showed that VB1 induce apoptosis via upregulating expression of cleaved-caspase3 and block cell cycle at G2/M phase through upregulating expression of P21. Meanwhile, VB1 can effectively inhibit tumor growth in xenograft mouse model. Our research indicated that VB1 can significantly exert its anti-neoplastic effects and may represent a new class of agents in ovarian cancer therapy.

SOX10 - A Novel Marker for the Differential Diagnosis of Breast Metaplastic Squamous Cell Carcinoma.

INTRODUCTION: Differential diagnosis of metaplastic squamous cell carcinoma of breast (MSCCB) is difficult. In particular, in terms of metastatic MSCCB, because of the low speciality of traditional markers such as mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15) and GATA binding protein 3 (GATA3), the most common problem is differentiating the spread of MSCCB to the lung from a primary lung squamous cell carcinoma. It is urgently required to explore a novel marker to aid in differential diagnosis. AIM: The aim of this study is to explore a novel marker to aid in the differential diagnosis of MSCCB from other squamous cell carcinomas (SCC) in other organs. METHODS: We tested the expression of SOX10 in 375 human SCC specimens with immunohistochemistry (IHC). RESULTS: In a series of 20 MSCCB, 9 (45%) were positive for SOX10. All of them were triple-negative MSCCB. Conversely, SOX10 was totally negative in another 205 SCC originating from lung, skin, cervix, oral mucosa, and esophagus. In a series of 150 triple-negative breast cancer and their metastatic foci, SOX10 labeling in the primary tumor and metastasis was 78% and 79.3%, respectively, and the agreement rate was 97.3% (P>0.05). CONCLUSION: Our findings demonstrate that SOX10 was recommended for differentiating MSCCB from non-mammary metastasis to the breast, as well as for distinguishing primary SCC from metastatic MSCCB, and SOX10 may be valuable in the pathological diagnosis of breast-derived metaplastic squamous cell carcinoma.