Development of a Prognostic Model Based on Differentially Expressed Immune Genes of Lung Adenocarcinoma

Due to the enormous heterogeneity and molecular complexity, the efficacy of existing lung adenocarcinoma risk prediction models were less than satisfactory. In this study, we downloaded the immune-related genes were from InnateDB, and the differentially expressed immune genes (DEIGs) were analyzed with edgeR and DESeq2 algorithm. In total, 1359 DEIGs were identified. Cytoscape was employed to build a mRNA-miRNA-lncRNA network which was consists of 8 lncRNAs, 7 miRNAs and 117 DEIGs. Functional enrichment analysis indicated that the 117 DEIGs were involved in immune and inflammatory responses and actively involved in a MAPK signaling pathway. A prognostic signature based on ten DEIGs including ASPH, CAV1, FKBP4, GRIK2, FURIN, SLC6A8, FSCN1, CKAP4, HAPLN2 and IL22RA2 which performed well was correlated with tumor burden, tumor stage and metastasis. The similar result was obtained in the validation dataset GSE72094 (p<0.0001). The prognostic index reflected infiltration by B cell, CD4+T cell, CD8+T cell and dendritic cell. We also found that ASPH and FSCN1 were over-expression in A549, H1299, PC-9 cells, and the positive expression of ASPH, FSCN1, MS4A1 and CD40LG had a correlation with the TNM stage, cellular differentiation and the lymphnode metastasis(p<0.05). High levels of ASPH and FSCN1, low levels of MS4A1 and CD40LG expression are all associated with poor overall survival in LUAD (p<0.05). In conclusion, our results identified DEIGs of clinical significance, verified the effect of the DEIGs-based, personalized prediction model for lung adenocarcinoma prognosis. Together, our results revealed that ASPH and FSCN1 could be a prognostic marker for lung adenocarcinoma.

Evaluation of Molecular Targets and Mismatch Repair Deficiency in Gallbladder Cancer

PurposeGallbladder cancer (GBC) is most aggressive malignancy having very short survival having heterogeneous incidence, clinical and molecular profile. We evaluated molecular targets and mismatch-repair (MMR) protein expression in North-Indian patients. Method111 cases were subjected to high-resolution melt curve, followed by Sanger sequencing for KRAS, BRAF and PIK3CA. Immunohistochemistry was done for four MMR proteins. ResultsSix (5.4%) cases showed KRAS mutation while no mutation was found in BRAF and PIK3CA. Deficient MMR was seen in 27.6% of GBC. All KRAS mutant cases were >50 years having higher perineural invasion (67%), lymphnode metastasis (67%) and stage-III disease (67%). MMR deficient GBC were significantly associated with well differentiated histology. KRAS mutant GBC had shorter mean survival than wild patients. MMR deficient GBC showed longer mean survival than MMR proficient cases. 10% of MMR deficient compared to 4% MMR proficient GBC showed KRAS mutation. ConclusionKRAS mutation was lower in North Indian patients despite having high GBC incidence making these patients suitable for targeted therapy. It was associated with poor prognostic factors and lower mean survival. MMR deficiency was higher and harbored predominantly well-differentiated histology with higher mean survival. Molecular targets and MMR expression in GBC may guide towards more appropriate approach in these patients.

The molecular mechanisms of the long noncoding RNA SBF2-AS1 in regulating the proliferation of oesophageal squamous cell carcinoma

The long noncoding RNASBF2-AS1 can promote the occurrence and development of many kinds of tumours, but its role in oesophageal squamous cell carcinoma (ESCC) is unknown. We found that SBF2-AS1 was up-regulated in ESCC, and its expression was positively correlated with tumor size (P = 0.0001), but was not related to gender, age, TNM stage, histological grade, and lymphnode metastasis (P > 0.05). It was further found that the higher the expression of SBF2-AS1, the lower the survival rate. COX multivariate analysis showed that the expression of SBF2-AS1 was an independent prognostic factor. Functional experiments show that inhibition of SBF2-AS1 can inhibit the proliferation of ESCC through in vivo and in vitro, and overexpression of SBF2-AS1 can promote the proliferation of ESCC and inhibit its apoptosis. In mechanism, SBF2-AS1/miR-338-3P, miR-362-3P/E2F1 axis are involved in the regulation of ESCC growth. In general, SBF2-AS1 may be used as ceRNA to combine with miR-338-3P and miR-362-3P to up-regulate the expression ofE2F1, and ultimately play a role in promoting cancer. It may be used as a therapeutic target and a biomarker for prognosis.

Methylation profiles of genes in breast cancer luminal HER2-negative primary tumor during regional lymphnode metastasis

Aberrant methylation is strongly associated with development of cancer, but limited data exist on correlation between methylation and regional lymph node metastasis (RLNM). The aim of this research was to study using of methylation levels of WIF1, RASSF1A, CDO1 and MEST aberrant methylated genes in a primary breast cancer for prediction of regional lymph node metastases. We used MS-HRM (Methylation Sensitive High Resolution Melting) to assess methylation levels. The results were confirmed by pyrosequencing. The study included 66 women with LumA and 46 women with HER2- (LumB-), 22 and 26 of them had metastasis in at least one lymph node respectively. It was found that methylation levels between LumA and LumB subtypes differed significantly in genes: WIF1 (p<0.001), CDO1 (p=0.002) and MEST (p=0.033). In the Lum A subtype statistically significant differences in level of methylation of WIF1 gene between patients with metastases in RLNM and patients without metastases were found (p=0.03). Analysis of tumors longer than 2 cm in the LumA subtype, revealed an increase of statistical significance of WIF1 gene — p=0.009 (AUC (95%CI) = 0.76 (0.59−0.93)). In LumB- subtype RASSF1A, CDO1 and MEST had statistically significant differences in methylation level between groups (p=0.03, p=0.048 and p=0.045 respectively). ROC analysis showed that combining of three genes by logistic regression, AUC (95%CI) was 0.74 (0.6−0.88). Analysis of tumors longer than 2 cm, did not increase statistical significance for these genes (p=0.046; p=0.089 and p=0.076, respectively). Thus, the study of methylation in primary tumors may be useful for prediction of lymph node metastasis, as well as for better understanding of biological process inside breast cancer.

Submandibular Cervical Mass as the First Presenting Sign of FVPTC. A Case Report and Review of Literature

Submandibular cervical swellings can manifest with a wide range of differentials which could be congenital, infective, reactive, neoplastic, or metastatic in origin. Here we discuss a case of a 42 year old male patient, who initially presented with a painless mass in the right submandibular region with no other associated symptoms, which on further examination turned out to be metastatic lymphadenopathy. A thorough investigation of the neck was subsequently performed, which lead us to the diagnosis of follicular variant of papillary thyroid carcinoma with submandibular lymphnode metastasis. Thus, the consideration of a metastatic lymph node in the differential diagnosis is always mandatory in the case of a long standing, largely asymptomatic solitary mass in the lateral neck of an adult patient.

Serum Zinc deficiency in squamous cell carcinomas of oral and maxillofacial region: a risk factor to its development and metastasis

Background To explore whether serum Zinc deficiency (sZnd) is a promoter to the development and lymphonode metastasis of squamous cell carcinoma (SCC) of oral and maxillofacial region (OMF). Methods 610 patients with SCC were enrolled in the study group, the controls consisted of the same number of age-gender matched subjects without cancers, serum Zinc level (sZn) was tested in both groups and anyone whose sZn belowed reference interval was detected as having sZnd. Characteristics of SCCs were investigated. Different concentration of serum Zinc and prevalence of sZnd between the two groups were calculated using Chi-square test. The association between serum Zinc status and SCC with different T-stages and lymphonode metastasis was focused on research. Results The patients varied from 19 to 87 years with a mean age of 58.89±10.91 years. Oral cavity was the most commonly affected region. Males were involved predominantly with a ratio of 1.44:1 to females. The concentration of sZn in malignancies was 12.57±2.53 μmol/L, 17.87% suffered from sZnd; in the control group were 14.65±2.25 μmol/L and 4.75%. Decreased sZn and increased prevalence of sZnd in SCC were statistically significant to controls (p=0.000) . Increased incidence of sZnd and reduced level of sZn correlated significantly to the the progression and lymphnode metastasis of SCC (p<0.01).Conclusions sZnd was a possible predisposing indicator to the tumorigenesis of SCC and also a promoter to its aggravation and lymphonode metastasis, which should be considered as a factor in devising the treatment plannings.

lncRNA LUCAT1 acts as a potential biomarker and demonstrates malignant biological behaviors in gastric cancerlncRNA LUCAT1 acts as a potential biomarker and demonstrates malignant biological behaviors in gastric cancer

Gastric cancer(GC) remains the fourth-leading malignancy worldwide and has a high mortality rate.Accumulating evidence reveals that long noncoding RNAs (lncRNAs) play essential roles in tumorigenesis and metastasis and can be used as potential biomarkers for diagnosis and prognosis. The current study sought to define the lncRNA LUCAT1 and verify its malignant biological behaviors in GC. We conducted bioinformatic analysis to screen differentially expressed lncRNAs between GC tissue and paracancerous tissue. Gene expression profiles were downloaded from the National Center of Biotechnology Information Gene Expression Omnibus(GEO). Real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to verify LUCAT1 expression in both GC tissue and paracancerous tissue. Furthermore, the associations between LUCAT1 and clinical features were analyzed. In addition, the malignant behaviors of LUCAT1 in GC were investigated by knocking down LUCAT1 expression in the SGC7901 and AGS cell lines. The results indicated that LUCAT1 expression was obviously upregulated in GC samples compared with paracancerous tissue samples. Moreover, the expression pattern of LUCAT1 showed close correlations with tumor diameter (P<0.001), differentiation grade (P=0.026), and lymphnode metastasis(LNM)status (P=0. 020). In vitro, shRNA-mediated knockdown of LUCAT1 expression inhibited proliferation, migration, and invasion and led to S-phase cell cycle arrest and apoptosisin GC cells. Thus, the lncRNA LUCAT1 may be used as a potential biomarker for early signs of LNM in GC and may play a crucial role in the development of GC.

Lymphnode metastasis patterns in primary sites of hypopharyngeal cancer: A retrospective analysis from multicenter data.

e18559 Background: Understanding the pattern of lymph node metastasis (LNM) in hypopharyngeal cancers (HPC) could help both surgeons and radiologists make decisions in the management of cervical lymph node. Our objective is to identify the pattern of nodal spread and the relationship between features of primary tumor and LNM in HPC. Methods: 244 newly diagnosed HPC patients during 2014 to 2017 were recruited from 3 specialized cancer hospitals in mainland China. All patients underwent head and neck magnetic resonance imaging(MRI) and received definitive radiotherapy ± concurrent chemotherapy. The features of primary tumor (tumor size, primary location, and extent of invasion) and the involvement of lymph nodes in each level were reassessed. According to the incidence of LNM, these levels were sequenced and sorted into drainage stations. Meanwhile, univariate and multivariate analysis was used to determine the risk factors for bilateral and regional lymph node metastasis. Results: The cohort consisted 195 piriform sinus cancers (PSC), 47 posterior wall cancers (PWC), 2 Post-cricoid cancers (PCC). 176 patients (72.1%) presented with MRI-detectable LNM. The overall LNM rates for level II-VI and retropharyngeal lymph nodes (RPLNs) were 59.0%, 52.9%, 14.3%, 1.6%, 2.9% and 14.7% respectively. Based on the prevalence of LNM in each level, we suppose that the lymphatic drainage of PSC was carried out in sequence along three stations: Level II & III (61.0% & 55.4%), Level IV & RPLN (15.9% & 10.3%), and Level V & VI(1.5% & 3.1%). While, for PWC the lymphatic drainage is carried out along two stations: Level II, III & RPLN (48.9%,40.4% & 34.0%), and Level IV-VI (6.4%, 0% and 2.1%). According to univariate analysis, primary subsite, posterior wall, post-cricoid and non-pyriform sinus invasion were correlated with bilateral LNM. The presence of RPLNs was correlated with larger tumor size(>4cm), primary subsite, posterior wall and non-pyriform sinus invasion. In further multivariate analysis, posterior wall invasion was significantly correlated with bilateral LNM (P = 0.030, HR = 2.853 95%CI, 1.110-7.338). Tumor size > 4cm(P = 0.017, HR = 2.545, 95%CI,1.180-5.488) and posterior wall invasion(P = 0.017, HR = 2.880 95%CI, 1.209-6.862) were correlated with RPLN metastasis. Conclusions: Different primary sites of HPC have different lymphnode metastasis patterns. Piriform sinus cancer tends to metastasize to the ipsilateral Level II&III. Posterior wall cancer tends to metastasize bilaterally to Level II, III and RPLN.