Numerous studies have reported expressions of immunoglobulins (Igs) in many human tumor tissues and cells. Tumor-derived Igs have displayed multiple significant functions which are different from classical Igs produced by B lymphocytes and plasma cells. This review will concentrate on major progress in expressions, functions, and mechanisms of tumor-derived Igs, similarities and differences between tumor-derived Igs and B-cell-derived Igs. We also discuss the future research directions of tumor-derived Igs, including their structural characteristics, physicochemical properties, mechanisms for rearrangement and expression regulation, signaling pathways involved, and clinical applications.

N. gonorrhoeaeandN. meningitidis, the only two human pathogens ofNeisseria, are closely related species. But the niches they survived in and their pathogenic characteristics are distinctly different. However, the genetic basis of these differences has not yet been fully elucidated. In this study, comparative genomics analysis was performed based on 15N. gonorrhoeae, 75N. meningitidis, and 7 nonpathogenicNeisseriagenomes. Core-pangenome analysis found 1111 conserved gene families among them, and each of these species groups had opening pangenome. We found that 452, 78, and 319 gene families were unique inN. gonorrhoeae,N. meningitidis, and both of them, respectively. Those unique gene families were regarded as candidates that related to their pathogenicity and niche adaptation. The relationships among them have been partly verified by functional annotation analysis. But at least one-third genes for each gene set have not found the certain functional information. Simple sequence repeat (SSR), the basis of gene phase variation, was found abundant in the membrane or related genes of each unique gene set, which may facilitate their adaptation to variable host environments. Protein-protein interaction (PPI) analysis found at least five distinct PPI clusters inN. gonorrhoeaeand four inN. meningitides, and 167 and 52 proteins with unknown function were contained within them, respectively.

Background: Immunoglobulin lambda (Igλ) has been reported to be expressed in many normal and tumor tissues and cells. However, the function and clinical significance of tumor-derived Igλ remain unclear. Methods: The differential expressions of Immunoglobulin Lambda Constants (IGLCs) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) were examined with The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) databases. The effects of IGLCs on patient clinical phenotypes and prognosis were explored via bioinformatics analyses based on the TCGA databases. We used the bioinformatics analyses based on the TCGA and GTEx databases to elucidate the correlations among IGLC expressions, immunomodulator expressions, tumor stemness, and infiltration scores of tumor infiltrating immune cells. Co-immunoprecipitation (Co-IP) and silver staining combined with liquid chromatography-tandem mass spectrometry (LC–MS/MS) were used to obtain potential tumor-derived Igλ-interacting proteins. Functional annotation of candidate proteins identified by LC–MS/MS was performed in Database for Annotation, Visualization and Integrated Discovery (DAVID). The bioinformatics analyses of 7 IGLCs in CESC and normal cervical tissues were performed based on TCGA, GTEx, and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases. Protein–protein interaction (PPI) network was analyzed based on tumor-derived Igλ-interacting proteins in Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Immunohistochemistry (IHC) was used to validate the expressions of IGLCs in CESC. Results: We found that the expressions of the majority of IGLCs (IGLC1, IGLC2, IGLC3, IGLC4, IGLC5, IGLC6, and IGLC7) were upregulated in CESC tissues, compared with those in normal cervical tissues. The expressions of IGLC5 and IGLC7 had significant difference in different pathologic metastasis (M), one of tumor, node, and metastasis (TNM) staging system, categories of CESC. Except for disease-free interval (DFI), 4 IGLC (IGLC1, IGLC2, IGLC3, and IGLC7) expression levels were positively associated with patient overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) respectively in CESC tissues. 5 IGLC (IGLC1, IGLC2, IGLC3, IGLC6, and IGLC7) expressions were positively correlated with the expressions of a majority of immunomodulators respectively in CESC tissues. Tumor stemness was negatively correlated with the expressions of 4 IGLCs (IGLC1, IGLC2, IGLC3, and IGLC7) respectively in CESC tissues. Except for IGLC4, IGLC5, and IGLC7, 4 IGLC (IGLC1, IGLC2, IGLC3, and IGLC6) expressions were positively correlated with infiltration scores of 6 tumor-infiltrating immune cells (B cell, T cell CD4, T cell CD8, neutrophil, macrophage, and DC). After analyses of the above bioinformatics data of tumor-derived Igλ, Co-IP and LC–MS/MS were used to confirm that 4 proteins (RPL7, RPS3, H1-5, and H1-6) might interact with tumor-derived Igλ in cervical cancer cells. Functional analyses of these candidate proteins showed that they interacted with many proteins and were involved in various cellular biological processes. Finally, IHC was used to further confirm the above bioinformatics results, it was indicated that the expression level of Igλ in cervical adenocarcinoma and cervical squamous cell carcinoma was higher than that in normal cervical tissue. Conclusion: This study comprehensively investigated the functions of tumor-derived Igλ and its interacting proteins based on bioinformatics analysis and the potential value of Igλ as a prognostic and therapeutic marker for CESC, providing new direction and evidence for CESC therapy.

Background: Immunoglobulin lambda (Igλ) has been reported to be expressed in many normal and tumor tissues and cells. However, the function and clinical significance of tumor-derived Igλ remain unclear. Methods: The differential expressions of IGLCs in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) were examined with The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) databases. The effects of IGLCs on patient clinical phenotypes and prognosis were explored via bioinformatics analyses based on the TCGA databases. We used the bioinformatics analyses based on the TCGA and GTEx databases to elucidate the correlations among IGLC expressions, immunomodulator expressions, tumor stemness, and infiltration scores of tumor infiltrating immune cells. Co-immunoprecipitation (Co-IP) and silver staining combined with and liquid chromatography-tandem mass spectrometry (LC-MS/MS)were used to obtained potential tumor-derived Igλ-interacting proteins. Functional annotation of candidate proteins identified by MS was performed in Database for Annotation, Visualization and Integrated Discovery (DAVID). The bioinformatics analysises of 7 IGLCs in CESC and normal cervical tissues was performed based on TCGA, GTEx, and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases. Protein-protein interaction (PPI) network was analyzed based on tumor-derived Igλ-interacting proteins in Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Immunohistochemistry (IHC) was used to validate the expressions of IGLCsin CESC. Results: we found that the expressions of the majority of Igλ constants (IGLC1, IGLC2, IGLC3, IGLC4, IGLC5, IGLC6, and IGLC7) were upregulated in CESC tissues, compare with those in normal cervical tissues. The expressions of all IGLCs had no significant difference in different pathological variables (stages, grades, age, and TNM) of CESC. Except for disease-free interval (DFI), 4 IGLC (IGLC1, IGLC2, IGLC3, and IGLC7) expression levels were positively associated with patient overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) respectively in CESC tissues. 5 IGLC (IGLC1, IGLC2, IGLC3, IGLC6, and IGLC7) expressions were positively correlated with the expressions of a majority of immunomodulators respectively in CESC tissues. Tumor stemness was negatively correlated with the expressions of 4 IGLCs (IGLC1, IGLC2, IGLC3, and IGLC7) respectively in CESC tissues. Except for IGLC4, IGLC5, and IGLC7, 4 IGLC (IGLC1, IGLC2, IGLC3, and IGLC6) expressions were positively correlated with infiltration scores of 6 tumor-infiltrating immune cells (B cell, T cell CD4, T cell CD8, neutrophil, macrophage, and DC). After analysisesof the above bioinformatics data of tumor-derived Igλ, Co-IP and LC-MS/MS were used to confirm that 4 proteins (RPL7, RPS3, H1-5, and H1-6) might interact with tumor-derived Igλ in cervical cancer cells. Functional analysises of these candidate proteins showed that they interacted with many proteins and were involved in various cellular biological processes. Finally, IHC was used to further confirm the above bioinformatics results, it was indicated that the expression level of Igλ in cervical adenocarcinoma and cervical squamous cell carcinoma was higher than that in normal cervical tissue. Conclusion: This study comprehensively investigated the functions of tumor-derived Igλand its interacting proteins based on bioinformatics analysisand the potential value of Igλ as a prognostic and therapeutic marker for CESC, providing new direction and evidence for CESC therapy.

Background: Esophageal cancer is one of the most common malignant tumors in the digestive system. Comprehensive treatment measures are mainly taken with surgery as the primary supplement to radiotherapy and chemotherapy, but the overall effect is still unsatisfactory. The tripartite motif containing 56 (TRIM56) is a family of TRIM proteins, and it has been found to play an essential role in tumorigenesis and development. We investigated the expression of TRIM56 in esophageal cancer and explored the potential regulatory role of TRIM56 in autophagy in esophageal cancer cells Eca109. Results: In this study, quantitative real-time PCR (qRT-PCR) assay, western blot (WB) and immunofluorescence (IF) were first used to detect the expression of TRIM56 in the Eca109 cells and esophageal cancer tissues. Gene chip analysis showed that the expression of autophagy-related genes LC3 and ATG12 was up-regulated, and regulated autophagy-related signal molecules PIK3CB, AKT2, and FOXO4 expression up-regulation after TRIM56 was down-regulated. Fluorescence immunoassay results showed that after TRIM56 was down-regulated, LC3BII aggregated in the cytoplasm. Conclusion: This study reveals that TRIM56 might inhibit autophagy in the Eca109 esophageal carcinoma cell line.