Constructing a prognostic model for colon cancer: insights from immunity-related genes.

BACKGROUND: Colon cancer (CC) is a malignancy associated with significant morbidity and mortality within the gastrointestinal tract. Recurrence and metastasis are the main factors affecting the prognosis of CC patients undergoing radical surgery; consequently, we attempted to determine the impact of immunity-related genes. RESULT: We constructed a CC risk model based on ZG16, MPC1, RBM47, SMOX, CPM and DNASE1L3. Consistently, we found that a significant association was found between the expression of most characteristic genes and tumor mutation burden (TMB), microsatellite instability (MSI) and neoantigen (NEO). Additionally, a notable decrease in RBM47 expression was observed in CC tissues compared with that in normal tissues. Moreover, RBM47 expression was correlated with clinicopathological characteristics and improved disease-free survival (DFS) and overall survival (OS) among patients with CC. Lastly, immunohistochemistry and co-immunofluorescence staining revealed a clear positive correlation between RBM47 and CXCL13 in mature tertiary lymphoid structures (TLS) region. CONCLUSION: We conclude that RBM47 was identified as a prognostic-related gene, which was of great significance to the prognosis evaluation of patients with CC and was correlated with CXCL13 in the TLS region.

The potential of EZH2 expression to facilitate treatment choice in stage II colorectal adenocarcinoma.

BACKGROUND: The current selection criteria of patients with stage II colorectal carcinoma (CRC) suitable for adjuvant therapy are not satisfactory. Enhancer of zeste homolog 2 (EZH2) has been demonstrated to be over-expressed in CRC. However, data regarding the role of EZH2 in CRC survival remains controversial, and little is known about it in stage II CRC. Thus, we conducted this study to investigate the clinical significance of EZH2 expression in stage II CRC. METHODS: Cases with stage II CRC resected between 2015 and 2018 were retrospectively reviewed. EZH2 expression was analyzed by immunohistochemistry using tissue microarrays. The relationship between EZH2 expression and clinicopathological variables was analyzed. Survival curves were estimated by the Kaplan-Meier approach. RESULTS: We found high EZH2 expression in 134 of 221 analyzable stage II tumors (60.63%). No significant associations were observed between EZH2 expression and common clinicopathological factors. Survival analyses showed that cases receiving surgery alone had inferior overall survival (OS) than those receiving surgery and chemotherapy (P=0.0075) in stage II CRC with high EZH2 expression, however, metastasis-free survival (MFS) was similar between these two subgroups. Treatment choice had no impact on the survival of stage II CRC with low EZH2 expression. CONCLUSION: The OS of stage II CRC with high EZH2 expression improved more strikingly with surgery and adjuvant chemotherapy than with surgery alone, which suggests the potential of EZH2 expression as a biomarker to help identify a subgroup of early-stage CRC benefiting from surgery and adjuvant chemotherapy. More large-scale studies are warranted to corroborate this finding and to further evaluate the predictive nature of EZH2.

Clinical outcomes of revision radical mastoidectomy surgeries to dry ears: A retrospective study.

This study retrospectively investigated the reasons for failure to dry the ear after primary radical mastoidectomy for chronic otitis media. In this retrospective study, we analyzed the main causes of dry ear failure in 43 patients (46 ears) who underwent radical mastoidectomy. We found that inadequate exposure of the mastoid cavity, incomplete removal of pathological tissues, and poor drainage of the surgical cavity were the main reasons for failure of radical mastoidectomy. Lesions in the tympanic ostium of the eustachian tube and incorrect selection of surgical techniques could also cause dry ear failure. Revision surgery based on preoperative temporal bone computed tomography and intraoperative surgical findings could achieve dry ear in 100% of cases and no complications were observed. In patients who underwent tympanoplasty, there was a significant postoperative decrease in the decibel hearing level for the air conduction threshold and air-bone gap ( P  < .05). Based on the reasons for failure, the corresponding treatment was undertaken to achieve dry ears during revision surgery.

Construction of hematoxylin-eosin, immunohistochemistry, and EBER-ISH methodology after trichloroisocyanuric acid treatment in melanin-containing tissues.

This study investigated the effects of trichloroisocyanuric acid (TCCA) on the bleaching and morphology of melanin-containing pathological sections. The pathological sections of 27 patients with high melanin content were bleached with 0.5% potassium permanganate, 10% hydrogen peroxide, and different concentrations of TCCA. Significant differences were found among the blank control group, 1% TCCA group (P < 0.0001). The hematoxylin-eosin (HE) score of the "recovery pH" HE staining group after treatment with 1% TCCA was similar to that of the "Conventional HE" scheme group (P > 0.05). The morphological diagnostic scores of 50 cases of pathological sections with different melanin content before and after TCCA bleaching were compared. The results showed a significant difference in the diagnostic score between the middle- and high-melanin content groups before and after 1% TCCA bleaching (P < 0.05). Immunohistochemical staining was performed on meningeal melanoma tissue. For this, 8% TCCA solution was used to remove melanin after Ki67, S100, and ß-catenin immunohistochemical staining. After bleaching with TCCA, the staining and positioning of each marker with different localization were accurate and the background was clear. The same results were also shown with EBER-ISH. This study concluded that 1% TCCA could be used for HE staining of pathological sections containing melanin, and "restore pH" HE scheme as the staining method after TCCA melanin removal. Further, 8% TCCA was used for bleaching after immunohistochemical DAB staining. Melanin can be completely removed, and sections can meet diagnostic needs.

HB-EGF Activates the EGFR/HIF-1α Pathway to Induce Proliferation of Arsenic-Transformed Cells and Tumor Growth.

Arsenic was recently identified as a pollutant that is a major cause of lung cancer. Since heparin-binding EGF-like growth factor (HB-EGF) was reported to be a promising therapeutic target for lung cancer, we investigated the role and mechanism of HB-EGF during arsenic-induced carcinogenesis and development of lung cancer. HB-EGF expression were upregulated in As-T cells, lung cancer cell lines, and in most lung cancer tissue samples; and HB-EGF activated the EGFR/p-ERK/HIF-1α pathway and induced VEGF by regulating HIF-1α transcription. HIF-1α transcriptional stimulation by HB-EGF was facilitated by PKM2 and played an important role in HB-EGF's effect on cells. An HB-EGF inhibitor(CRM197, cross-reacting material 197) slowed cell proliferation and inhibited migration of As-T and A549 cells, and inhibited tumor growth. PKM2 also played an important role in the proliferation and migration in As-T cells. The positive staining ratios of EGFR phosphorylation (Y1068) and PKM2 were significantly higher in most cases of lung cancer than in paired normal tumor-adjacent lung tissues; and HB-EGF expression levels strongly correlated with p-EGFR expression levels. Thus, HB-EGF drives arsenic-induced carcinogenesis, tumor growth, and lung cancer development via the EGFR/PKM2/HIF-1α pathway.

MiR-381-3p suppresses biological characteristics of cancer in head-neck squamous cell carcinoma cells by targeting nuclear autoantigenic sperm protein (NASP).

MiR-381-3p and nuclear autoantigenic sperm protein (NASP) have regulatory functions in tumors. Whether NASP is targeted by miR-381-3p to influence biological characteristics of cancer in head-neck squamous cell carcinoma (HNSCC) cells was investigated. StarBase (version 3.0) found that the expression of NASP was increased with the down-regulation of miR-381-3p in laryngocarcinoma tissue, AMC-HN-3，FaDu，HNE-3，and Detroit 562 cell lines. MiR-381-3p could target NASP, reduce the expression of MMP-2 and MMP-9, Vimentin, repress the cell viability, invasion, and migration, and promote the expression of E-cadherin in AMC-HN-3 cells. Overexpressed NASP could increase the viability, migration and invasion rates in AMC-HN-3 cells, which could be partially reversed by overexpressed miR-381-3p. Thus, miR-381-3p targeted and suppressed NASP gene, reduced the viability, migration, invasion, EMT of HNSCC cells, demonstrating that miR-381-3p has the potential to be a therapeutic target in inhibiting the progression of HNSCC.

Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis.

The apoptosis that occurs in the immature testis under physiological conditions is necessary for male germ cell development, whereas improper activation of apoptosis can impair spermatogenesis and cause defects in reproduction. We previously demonstrated that in mice, the makorin-2 (Mkrn 2) gene is expressed exclusively in the testis and its deletion leads to male infertility. To understand the potential molecular mechanism, in this study, we found that levels of apoptosis in the testis were abnormally high in the absence of Mkrn 2. To identify specific gene(s) involved, we performed digital gene expression profiling (DGE) and pathway analysis via gene set enrichment analysis (GSEA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and we found that MKRN2 inhibits p53 apoptosis effector related to PMP22 (PERP) expression and that levels of the protein in sperm samples have an inverse correlation with infertility levels. GSEA additionally indicated that PERP is a negative regulator of spermatogenesis and that its ectopic expression induces male infertility. Further, Gene Expression Omnibus (GEO) dataset analysis showed that p53, upstream of PERP, was upregulated in oligoasthenoteratozoospermia (OAT). These observations suggest that Mkrn 2 is crucial for protecting germ cells from excessive apoptosis and implicate Mkrn 2-based suppression of the p53/PERP signaling pathway in spermatogenesis and male fertility.

Role of hypoxia-induced exosomes in tumor biology.

PURPOSE: Hypoxia is a major regulator of angiogenesis and always influences the release of exosomes in various types of tumors. The present review aimed to assess the role of hypoxia-induced exosomes in the tumor biology. METHODS: The relevant publications were retrieved from PubMed using keywords such as hypoxia, exosome, extracellular vesicles, tumor, cancer, and other similar terms. RESULTS: Recent studies have shown that cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. The secretion and function of exosomes could be influenced by hypoxia in various types of cancer. Hypoxia-induced exosomes play critical roles in tumor angiogenesis, invasion, metastasis, and the immune system. CONCLUSIONS: These findings provide new insights into the complex networks underlying cellular and genomic regulation in response to hypoxia and might provide novel and specific targets for future therapies.

MiR-598 Suppresses Invasion and Migration by Negative Regulation of Derlin-1 and Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer.

BACKGROUND/AIMS: MicroRNAs regulate a wide range of biological processes of non-small cell lung cancer (NSCLC). Although miR-598 has been reported to act as a suppressor in osteosarcoma and colorectal cancer, the physiological function of miR-598 in NSCLC remains unknown. In this study, the role of miR-598 in NSCLC was investigated. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to estimate the expression of miR-598 and Derlin-1 (DERL1) in both NSCLC tissues and cell lines. Immunohistochemistry (IHC) analyzed the association between the miR-598 expression and epithelial-mesenchymal transition (EMT) hallmark genes (E-cadherin, Vimentin) by staining the tumors representative of the high- and low-expression groups. The effect of miR-598 and DERL1 on invasion and migration was determined in vitro using transwell and wound-healing assays. The molecular mechanism underlying the relevance between miR-598 and DERL1 was elucidated by luciferase assay and Western blot. Western blot assessed the expression levels of EMT hallmark genes in cell lines. Xenograft tumor formation assay was conducted as an in vivo experiment. RESULTS: In this study, a relatively low level of miR-598 and high DERL1 expressions were found in NSCLC specimens and cell lines. IHC results established a positive correlation between the miR-598 expression and E-cadherin and a negative with Vimentin. DERL1 was verified as a direct target of miR-598 by luciferase assay. In vitro, the over-expression of miR-598 negatively regulated DERL1 and EMT for the suppression of invasion and migration. In vivo, the over-expression of miR-598 could inhibit tumor cell metastasis in NSCLC. CONCLUSIONS: These findings for the first time revealed that miR-598, as a tumor suppressor, negatively regulate DERL1 and EMT to suppress the invasion and migration in NSCLC, thereby putatively serving as a novel therapeutic target for NSCLC clinical treatment.