Lipopolysaccharide (LPS) from Helicobacter pylori (HP) plays an important role in gastric cancer occurrence and development. Toll-like receptor 4 (TLR4) and myeloid differential protein-2 (MD-2) are also reported to be involved in gastric cancer cell proliferation and invasion. CXC chemokine receptor 7 (CXCR7), a second receptor for CXCL12, has been detected in multiple types of tumor tissues. Nevertheless, the biological function and regulation of CXCR7 and its relationship with TLR4 and MD-2 in gastric cancer are not completely understood and therefore warrant further study. CXCR7 expression was examined in 150 gastric cancer tissues using immunohistochemistry (IHC). RT-PCR and western blotting were used to detect CXCR7 expression in several gastric cancer cell lines (SGC7901, AGS, MGC-803, MKN-45 and BGC823). shRNAs were designed using a pGPU6/GFP/Neo vector. A CCK-8 assay was used to assess cell proliferation, and transwell assays were performed to assess cell migration. In addition, a gastric cancer xenograft model was generated. The LPS-TLR4-MD-2 pathway elevates CXCR7 expression in SGC7901 cells, and TLR4/MD-2-mediated increases in CXCR7 levels modulate the proliferation and migration of tumor cells. Knockdown of TLR4 and MD-2 demonstrated that both are essential for LPS-induced CXCR7 expression, which in turn is responsible for LPS-induced SGC7901 cell proliferation and migration. Moreover, higher TLR4, MD-2 and CXCR7 expression was detected in gastric cancer tissues than in paracancerous normal control tissues. The expression levels of TLR4, MD-2 and CXCR7 were closely related to gastric cancer TNM stage and lymph node metastasis. In an animal model, significant differences in CXCR7 expression in tumor masses were observed between the control group and experimental group. The results of this study indicate that CXCR7 plays an important role in gastric cancer progression via inflammatory mechanisms, suggesting that CXCR7 could provide a basis for the development and clinical application of a targeted drug for gastric cancer.

Background: Oxaliplatin (OXA)-based chemotherapy is critical in the management of advanced hepatocellular carcinoma (HCC); however, acquired drug resistance has largely restricted its clinical efficacy. This study aims to explore the key mechanisms and regulatory factors determining chemosensitivity in HCC. Methods: We developed OXA-resistant (OR) HCC cells and used multiple methods, including real-time RT-PCR, Western blot, immunofluorescence, transwell invasion assay, wound-healing assay, MTT assay, gene transfection, and immunohistochemistry to achieve our goals. Results: We found that OR HCC cells showed a typical epithelial–mesenchymal transition (EMT) phenotype. Meanwhile, the expression of Cx32, a major member of the liver connexin (Cx) family, was lowly expressed in OR HCC cells. Downregulation of Cx32 in parental HCC cells led to EMT induction and thereby reduced OXA cytotoxicity, while Cx32 upregulation in OR HCC cells could reverse the EMT phenotype and partially restore chemosensitivity to OXA. Finally, in human HCC tissue samples, Cx32 was positively correlated with the expression of the EMT marker E-cadherin and negatively correlated with the expression of Vimentin. Conclusion: Our findings demonstrated that downregulation of Cx32 may be an important determinant for HCC cells to acquire EMT-related acquired drug resistance to OXA, and targeting Cx32 could be a novel strategy to overcome OXA resistance in HCC.

Background: PHD-finger domain protein 5A (PHF5A) is a highly conserved small transcriptional regulator also involved in pre-mRNA splicing; however, its biological functions and molecular mechanisms in non-small cell lung cancer (NSCLC) have not yet been investigated. The purpose of this study was to determine the functional relevance and therapeutic potential of PHF5A in lung adenocarcinoma (LAC). Methods: The expression of PHF5A in LAC tissues and adjacent non-tumor (ANT) tissues was investigated using immunohistochemistry of a tissue microarray, qRT-PCR, western blot and bioinformatics. The function of PHF5A was determined using several in vitro assays and also in vivo assay by lentiviral vector-mediated PHF5A depletion in LAC cell lines. Results: PHF5A was highly upregulated in LAC tissues compared with the ANT counterparts, and closely associated with tumor progression and poor patient prognosis. These results were further confirmed by findings of the TCGA database. Moreover, functional studies demonstrated that PHF5A knockdown not only resulted in reduced cell proliferation, increased cell apoptosis, and cell cycle arrest, but also suppressed migration and invasion in LAC cells. PHF5A silencing was also found to inhibit LAC tumor growth in nude mice. Microarray and bioinformatics analyses revealed that PHF5A depletion led to dysregulation of multiple tumor signaling pathways; selected factors in key signaling pathways were verified in vitro. Conclusions: The data suggest for the first time that PHF5A is an oncoprotein that contributes to LAC progression by regulating multiple signaling pathways, and may constitute a prognostic factor and potential new therapeutic target in NSCLC.

Interleukin-33 (IL-33), a newly-discovered cytokine belonging to the IL-1 family, serves an important role in inflammation. However, it is not clear whether IL-33 is of clinical significance in hepatocarcinogenesis. The present study was designed to investigate the role of IL-33 during oncogenesis and development of hepatocellular carcinoma (HCC). IL-33 protein expression was detected in 76 HCC (including 36 para-carcinoma), 33 cirrhosis, 30 hepatitis, and 20 normal liver tissues using immunohistochemistry. IL-33 mRNA expression in carcinoma and para-carcinoma tissues was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). The possible correlation between IL-33 and clinicopathological parameters of HCC was also analyzed. Significant differences in IL-33 expression were not observed among normal, hepatic, and cirrhotic tissues (P> 0.05), whereas the level of protein positive rate was markedly reduced in HCC tissues (P< 0.01). Positive staining of IL-33 in non-cancerous liver (NCL) tissues (i. e. normal, hepatitis, and liver cirrhosis) was located predominantly in the nucleus and occasionally in the cytoplasm of hepatocytes; however, the expression in HCC tissues was mostly restricted to the cytoplasm. A significant alteration in protein localization was observed in HCC tissues as compared with NCL tissues (P< 0.01). In comparison with HCC tissues, cytoplasmic staining of IL-33 was increased in para-carcinoma tissues. RT-PCR assay further confirmed relatively high mRNA expression levels of IL-33 in para-carcinoma tissues. IL-33 expression was significantly negatively associated with tumor histological grade (r=-0.279, P=0.015), but not with year, gender, tumor size, clinical stage, HCC with hepatitis and cirrhosis background, lymph node metastasis or intrahepatic vascular embolism (P> 0.05). Therefore, the aberrant expression of IL-33 is associated with oncogenesis and progression of HCC and the cytoplasmic accumulation of the protein may serve a role in hepatocarcinogenesis.

Metabolic reprogramming and immune evasion synergistically drive breast carcinogenesis, but their combined impact remains unclear. Transcriptomic data from the TCGA and GEO cohorts were integrated. Differentially expressed genes were identified, followed by WGCNA to detect immune-correlated co-expression modules. Immune-metabolism-related genes (IMGs) were screened using Genecards. Four machine learning algorithms (LASSO, SVM, RF, XGBoost) identified hub genes. The diagnostic value was evaluated by Kaplan-Meier and ROC analysis. CIBERSORT quantified immune microenvironment associations. The expression profiles of genes in different cells were plotted using single-cell RNA data. IHC validated protein expression in clinical samples. Research has found that SELENOP and PKMYT1 are key immune metabolic hubs. Compared with normal tissues, the expression of SELENOP was significantly decreased (p < 0.05), while PKMYT1 showed an upward trend (p < 0.05). Both of these genes have demonstrated high accuracy in the diagnosis of breast cancer and can effectively predict the overall survival period of patients. Low SELENOP expression is associated with high PKMYT1 expression levels, which is significantly related to changes in immune infiltration and the expression patterns of checkpoint proteins. Immunohistochemical detection further confirmed that these genes were significantly correlated with histological grade, LAG-3, CD244, ER, PR and Her-2 and other indicators (p < 0.05). SELENOP and PKMYT1 are novel immunomodulatory factors related to multiple pathological indicators of breast cancer and can be used as diagnostic biomarkers.

Background: The expression of RKIP, TGM2, and CMTM4 in oral squamous cell carcinoma (OSCC) and normal oral tissues was detected and their correlations were analyzed. The relationships between RKIP, TGM2, and CMTM4 and the clinicopathological parameters and prognosis of patients were analyzed. Methods: Seventy cancerous and adjacent normal tissue samples were selected, recorded in the pathology department, and embedded in paraffin. Protein expression was detected by immunohistochemistry. Statistical software (SPSS 25.0, IBM Corporation) was used for the statistical analysis. The chi-squared (χ²) test was used to analyze the expression of RKIP, TGM2, and CMTM4 proteins and their clinicopathological features. Differences in RKIP, TGM2, and CMTM4 protein levels between OSCC and normal tissues were compared using a χ² test. Survival analysis was performed using the Kaplan–Meier method, and differences between survival curves were determined using the log-rank test. The effects of RKIP, TGM2, and CMTM4 expression on patient prognosis were analyzed using a multivariate Cox proportional hazards regression model. P < .05 was considered statistically significant. Results: The expression level of RKIP correlated with age and clinical stage (P < .05). TGM2 was associated with clinical stage and lymph node metastasis (P < .05). The expression of CMTM4 increased with a decrease in cancer differentiation. Kaplan–Meier survival analysis suggested that the positive expression of TGM2 and CMTM4 may predict poor prognosis in patients with OSCC. The multivariate Cox proportional hazards regression model suggested that TGM2 could be an independent prognostic factor for patients with OSCC. Conclusion: Combined expression of TGM2 and CMTM4 can be used as an indicator to evaluate the risk of metastasis and prognosis of OSCC.