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Background: Pervasive transcription of the eukaryotic genome generates noncoding RNAs (ncRNAs), which regulate messenger RNA (mRNA) stability and translation. MicroRNAs (miRNAs/miRs) represent a group of well-studied ncRNAs that maintain cellular homeostasis. Thus, any aberration in miRNA expression can cause diseases, including carcinogenesis. According to microRNA microarray analyses, intronic miR-617 is significantly downregulated in oral squamous cell carcinoma (OSCC) tissues compared to normal oral tissues. Methods: The miR-617-mediated regulation of DDX27 is established by performing experiments on OSCC cell lines, patient samples, and xenograft nude mice model. Overexpression plasmid constructs, bisulphite sequencing PCR, bioinformatics analyses, RT-qPCR, Western blotting, dual-luciferase reporter assay, and cell-based assays are utilized to delineate the role of miR-617 in OSCC. Results: The present study shows that miR-617 has an anti-proliferative role in OSCC cells and is partly downregulated in OSCC cells due to the hypermethylation of its independent promoter. Further, we demonstrate that miR-617 upregulates DDX27 gene by interacting with its promoter in a dose-dependent and sequence-specific manner, and this interaction is found to be biologically relevant in OSCC patient samples. Subsequently, we show that miR-617 regulates cell proliferation, apoptosis, and anchorage-independent growth of OSCC cells by modulating DDX27 levels. Besides, our study shows that miR-617 exerts its effects through the PI3K/AKT/MTOR pathway via regulating DDX27 levels. Furthermore, the OSCC xenograft study in nude mice shows the anti-tumorigenic potential of miR-617. Conclusion: miR-617-mediated upregulation of DDX27 is a novel mechanism in OSCC and underscores the therapeutic potential of synthetic miR-617 mimics in cancer therapeutics. To the best of our knowledge, miR-617 is the 15th example of a miRNA that upregulates the expression of a protein-coding gene by interacting with its promoter. [ABSTRACT FROM AUTHOR]

Introduction: Extragonadal germ cell tumors (EGGCTs) are tumors arising at extragonadal ana-tomical locations. The biological behavior and prognosis of these tumors differ from their gonadal counterparts. Our study aims to analyze their histological subtypes, the outcome, and the prognosis of these lesions at various age groups. Material and Methods: We carried out a retrospective analysis of all patients with EGGCTs diag-nosed from January 2017 to December 2019. Results: Our study included 61 cases of EGGCTs. These cases were divided into neonatal (birth to six months), prepubertal (more than six months to 12 years), and post-pubertal group (>12 years). The most frequently affected group was prepubertal (44.2%). The age ranged from birth to 45 years with a male-to-female ratio of 1:1.03. The frequently involved site was sacrococcyx (36%) followed by mediastinum (31.1%). The common histologic subtype was mature teratoma (39.3%), followed by yolk sac tumor (YST) (18%), mixed germ cell tumor (18%), immature teratoma (14.7%), and germinoma (9.8%). Four cases of teratoma had somatic malignancies. There were 48 stage I, 8 stage II, and 2 stage III tumors. Statistical analysis revealed a significant association of age group concerning primary site (p=0.004), histological type (p=0.002), and clinical stage (p=0.034). In a median follow-up of 30 months, an Overall Survival (OS) of 93.2% and Event Free Survival (EFS) of 90.4% were noted across all age groups. OS of 100% (neonatal), 96% (prepubertal) and 88.0% (post-pubertal) revealing a declining trend (p=0.324) with increasing age was noted. The important prognostic factors include histological subtype (mixed germ cell tumors and teratomas with somatic malignancies had reduced overall survival) and stage (I vs II and III) for OS and stage alone for EFS (P<0.0001). Conclusion: Our study highlights the clinicopathological characteristics, prognostic parameters, and the outcome of GCTs occurring at extragonadal sites and emphasizes the role of pathologists in the detailed reporting of these lesions. [ABSTRACT FROM AUTHOR]

Background: Fine-needle aspiration cytology plays role in preoperative diagnosis of any salivary gland mass lesions. Because of heterogeneity of salivary gland lesions and cytomorphology overlap, a uniform 6-tier Milan classification proposed which could be helpful in better communication of reports for patient's management. Methods: Study included 4 years (2011–2015) retrospective data retrieval from cytology department of our Institute, which is a tertiary care cancer center of South India. Histopathology correlation was done wherever possible. Result: Total 253 cases were studied. Histopathological follow-up was available in 115 cases. Cases were categorized as nondiagnostic (1.58%), nonneoplastic (13.43%), benign (30%), atypia (0.8%), and suspicious for malignancy and malignant cytology (51.8%). The risk for malignancy was high for suspicious for malignancy and malignant cytological categories ranged from 96–100%. The sensitivity, specificity, and accuracy for diagnosing malignancy varied from 86.76%, 93.75%, and 89%, respectively. Conclusion: Risk stratification approach in classifying salivary gland cytology aspirate as per Milan system provides a standardized reporting and better communication to clinician. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) remains a leading cause of cancer-related mortality globally. This is due to the fact that majority of the cases of GC are diagnosed at an advanced stage when the treatment options are limited and prognosis is poor. The diffuse subtype of gastric cancer (DGC) under Lauren's classification is more aggressive and usually occurs in younger patients than the intestinal subtype. The concept of personalized medicine is leading to the identification of multiple biomarkers in a large variety of cancers using different combinations of omics technologies. Proteomic changes including post-translational modifications are crucial in oncogenesis. We analyzed the phosphoproteome of DGC by using paired fresh frozen tumor and adjacent normal tissue from five patients diagnosed with DGC. We found proteins involved in the epithelial-to-mesenchymal transition (EMT), c-MYC pathway, and semaphorin pathways to be differentially phosphorylated in DGC tissues. We identified three kinases, namely, bromodomain adjacent to the zinc finger domain 1B ( BAZ1B ), WNK lysine-deficient protein kinase 1 ( WNK1 ), and myosin light-chain kinase ( MLCK ) to be hyperphosphorylated, and one kinase, AP2-associated protein kinase 1 ( AAK1 ), to be hypophosphorylated. LMNA hyperphosphorylation at serine 392 (S392) was demonstrated in DGC using immunohistochemistry. Importantly, we have detected heparin-binding growth factor ( HDGF ), heat shock protein 90 ( HSP90 ), and FTH1 as potential therapeutic targets in DGC, as drugs targeting these proteins are currently under investigation in clinical trials. Although these new findings need to be replicated in larger study samples, they advance our understanding of signaling alterations in DGC, which could lead to potentially novel actionable targets in GC.