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Background: Junctional adhesion molecule 2 (JAM2) plays a pivotal role in various biological processes, including proliferation, metastasis and angiogenesis, contributing to tumor progression. While previous studies have highlighted the polarizing functions of JAM2 in different cancer types, its specific role in lung adenocarcinoma (LUAD) remains unclear. Methods: In this study, we harnessed multiple public databases to analyze the expression and prognostic significance of JAM2 in LUAD. Using the Linkedomics database, Matescape database and R package, we explored the associated genes, the potential biological functions and the impact of JAM2 on the tumor microenvironment. Our findings from public databases were further validated using real‐time quantitative PCR, western blot and immunohistochemistry. Additionally, in vitro experiments were conducted to assess the influence of JAM2 on LUAD cell proliferation, invasion, migration, apoptosis and epithelial–mesenchymal transition. Furthermore, we established a xenograft model to investigate the in vivo effects of JAM2 on tumorigenesis. Results: Our results revealed a significant downregulation of JAM2 in LUAD, and patients with low JAM2 expression exhibited unfavorable overall survival outcomes. Functional enrichment analysis indicated that JAM2 may be associated with processes such as cell adhesion, extracellular matrix, cell junctions and regulation of proliferation. Notably, increased JAM2 expression correlated with higher tumor microenvironment scores and reduced immune cell abundance. Furthermore, overexpression of JAM2 induced apoptosis, suppressed tumor proliferation and exhibited potential inhibitory effects on tumor invasion and migration through the modulation of epithelial–mesenchymal transition. Additionally, in vivo experiments confirmed that JAM2 overexpression led to a reduction in tumor growth. Conclusion: Overall, our study highlights the clinical significance of low JAM2 expression as a predictor of poor prognosis in LUAD patients. Moreover, JAM2 was found to exert inhibitory effects on various aspects of tumor progression. Consequently, JAM2 emerges as a promising prognostic biomarker and a potential therapeutic target for LUAD patients. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the predictive value of 18F‐FDG PET/CT for pathological response after neoadjuvant immunochemotherapy (NICT) in patients with esophageal squamous cell carcinoma (ESCC). Methods: The clinical data of 54 patients with ESCC who underwent two cycles of NICT followed by surgery were retrospectively analyzed. NICT consisted of PD‐1 blockade therapy combined with chemotherapy. 18F‐FDG PET/CT scans were performed before and after NICT. The pathological results after surgery were used to assess the degree of pathological response. The scan parameters of 18F‐FDG PET/CT and their changes before and after NICT were compared with the pathological response. Results: Among the 54 patients, 10 (18.5%) achieved complete pathological response (pCR) and 21 (38.9%) achieved major pathological response (MPR). The post‐NICT scan parameters and their changes were significantly associated with the pathological response. In addition, the values of the changes in the scanned parameters before and after treatment can further predict the pathological response of the patient. Conclusion: 18F‐FDG PET/CT is a useful tool to evaluate the efficacy of NICT and predict pathological response in patients with ESCC. The post‐NICT scan parameters and their changes can help identify patients who are likely to achieve pCR or MPR. [ABSTRACT FROM AUTHOR]

Background: Tumor recurrence or residual tumor after targeted therapy is common in patients with advanced non‐small cell lung cancer (NSCLC). There is a lack of high‐level evidence on which type of treatment should be employed for these patients and the role of salvage surgery has not been well reported in the literature. Methods: A retrospective analysis of patients who underwent salvage surgery in our center between January 2016 and June 2019 for advanced NSCLC after targeted therapy was performed. Results: A total number of nine patients were identified, including five males and four females, with a median age of 56 years (range, 40–65 years), all diagnosed with lung adenocarcinoma stage IIIa–IVb. All patients had received targeted therapy according to individual positive mutation of driver gene(s). Salvage surgery was performed for tumor recurrence or residual tumor after a duration of 2–46 months of targeted therapy. A negative surgical margin was achieved in all cases. Postoperative complication rate was 11.1% (1/9). All patients were alive at the time of this analysis and two patients had disease progression. After a median follow‐up of 17 months (range: 5–44 months), the median event‐free survival and postoperative survival was 14 months (range: 2–44 months) and 17 months (range: 5–44 months) respectively. Conclusions: Salvage surgery may be a feasible and promising therapeutic option for tumor recurrence or residual tumor in advanced NSCLC in selective patients after targeted therapy. Key points: Salvage surgery is feasible in selected patients with advanced NSCLC and provides promising survival outcomes after targeted therapy failure.Salvage surgery provides precise molecular and pathological information which is most important for subsequent therapy. [ABSTRACT FROM AUTHOR]

Long intergenic non-coding RNA for kinase activation (LINK-A) has been characterized as an oncogenic long non-coding RNA (lncRNA) in triple-negative breast cancer. However, its involvement in non-small cell lung cancer (NSCLC) remains unknown. The aim of the present study was to investigate the involvement of LINK-A in NSCLC. Expression of LINK-A lncRNA in the plasma of patients with NSCLC collected on the day of admission and the day of discharge, and in the plasma of healthy controls, was detected by reverse transcription-quantitative PCR. Diagnostic values of plasma LINK-A for metastatic NSCLC were evaluated by receiver operating characteristic curve analysis. A LINK-A lncRNA expression vector was constructed and transfected into human NSCLC cell lines, and the effects on cell migration and invasion, and Akt activation were detected by Transwell and Matrigel assays, and western blotting, respectively. Plasma levels of LINK-A were found to be significantly higher in patients with different types of metastatic NSCLC than in patients with non-metastatic NSCLC and healthy controls. Plasma levels of LINK-A were lower in patients with metastatic NSCLC on the day of discharge than on the day of admission. Patients with high plasma LINK-A had a higher mortality rate and lower progression-free survival rate within 2 years of discharge. In conclusion, LINK-A is overexpressed in metastatic NSCLC, and may promote the migration and invasion of NSCLC by activating Akt signaling. [ABSTRACT FROM AUTHOR]

Previous studies proposed that CYP1A2 rs762551 polymorphism might be associated with risk of lung cancer by influencing the function of CYP1A2. However, previous studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer reported inconsistent findings. We performed a meta-analysis of the published case-control studies to assess the association between CYP1A2 rs762551 polymorphism and risk of lung cancer. PubMed and Embase were searched to identify relevant studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer, and seven studies with a total of 3,320 subjects were finally included into the meta-analysis. The pooled odds ratio (OR) and 95 % confidence interval (95%CI) was calculated to evaluate the association. Meta-analysis of total studies showed that CYP1A2 rs762551 polymorphism contributed to risk of lung cancer under all four genetic models (C versus A: OR = 1.26, 95%CI 1.13 to 1.40, P < 0.001; CC versus AA: OR = 1.61, 95%CI 1.28 to 2.04, P < 0.001; CC versus AA/AC: OR = 1.52, 95%CI 1.11 to 2.09, P = 0.009; CC/AC versus AA: OR = 1.28, 95%CI 1.10 to 1.48, P = 0.001). Subgroup analysis based on ethnicity further suggested that CYP1A2 rs762551 polymorphism was associated with risk of lung cancer in Caucasians. These results from the meta-analysis suggest that CYP1A2 rs762551 polymorphism contributes to risk of lung cancer. [ABSTRACT FROM AUTHOR]

Background: So far, the miRNAs involved in multidrug resistance of esophageal cancer have not been reported.Aims and Methods: Here we have firstly investigated the roles of miR-27a in multidrug resistance of esophageal squamous cell carcinoma using MTT assay, flow cytometry assay, and reporter gene assay, etc.Results: Down-regulation of miR-27a could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-non-related drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Down-regulation of miR-27a could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of the multidrug resistance gene 1, but up-regulate the expression of Bax.Conclusions: MiR-27a might play important roles in multidrug resistance of esophageal cancer. The further study of the biological functions of miR-27a might be helpful for developing possible strategies to treat esophageal cancer. [ABSTRACT FROM AUTHOR]

Tescalcin (TESC) is a critical regulator of cell differentiation and growth, promoting malignant progression in various tumors. However, the role of TESC in esophageal squamous carcinoma (ESCC) remains unclear. Immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and western blot were utilized to identify the difference in TESC expression between ESCC tissues and normal tissues adjacent to the carcinoma. The relationship between TESC and several clinicopathological features was shown by the chi-square test. Log-rank analysis and Cox regression were used to detect the relationship between TESC and the prognosis in ESCC. Clone formation and cell count kit-8 (CCK-8) were applied to detect the impact of TESC on ESCC proliferation. Wound healing assay and transwell assay were used to confirm the influence of TESC on the invasion and migration. Spearman correlation coefficient was used to describe the correlation between TESC and epithelial-mesenchymal transition (EMT)-related protein expression in ESCC. Western blot was used to detect the effect of TESC on the expression of E-cadherin, N-cadherin, and Vimentin as well as AKT signaling pathway. Xenograft tumors were developed to test the pro-tumorigenic impacts of TESC in vivo. TESC was upregulated expression in ESCC tissues and was linked to poorer prognosis and worse tumor infiltration, TNM stage, and lymph node metastasis. Meanwhile, TESC was able to act as an independent prognostic factor in ESCC. TESC promoted tumor cell proliferation, invasion, migration, EMT progression, and activated the phosphorylation of the AKT pathway. Furthermore, TESC knockdown inhibited the growth of carcinoma in vivo. TESC is a predictive factor for poor prognosis in ESCC and may provide a new strategy for ESCC treatment. [ABSTRACT FROM AUTHOR]

V-set and immunoglobulin domain containing 4 (VSIG4), a type I transmembrane receptor exclusively expressed in a subset of tissue-resident macrophages, plays a pivotal role in clearing C3-opsonized pathogens and their byproducts from the circulation. VSIG4 maintains immune homeostasis by suppressing the activation of complement pathways or T cells and inducing regulatory T-cell differentiation, thereby inhibiting the development of immune-mediated inflammatory diseases but enhancing cancer progression. Consequently, VSIG4 exhibits a potential therapeutic effect for immune-mediated inflammatory diseases, but also is regarded as a novel target of immune checkpoint inhibition in cancer therapy. Recently, soluble VSIG4, the extracellular domain of VSIG4, shed from the surface of macrophages, has been found to be a biomarker to define macrophage activation-related diseases. This review mainly summarizes recent new findings of VSIG4 in macrophage phagocytosis and immune homeostasis, and discusses its potential diagnostic and therapeutic usage in infection, inflammation, and cancer. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the predictive value of 18 F-FDG PET/CT for pathological response after neoadjuvant immunochemotherapy (NICT) in patients with esophageal squamous cell carcinoma (ESCC)., Methods: The clinical data of 54 patients with ESCC who underwent two cycles of NICT followed by surgery were retrospectively analyzed. NICT consisted of PD-1 blockade therapy combined with chemotherapy. 18 F-FDG PET/CT scans were performed before and after NICT. The pathological results after surgery were used to assess the degree of pathological response. The scan parameters of 18 F-FDG PET/CT and their changes before and after NICT were compared with the pathological response., Results: Among the 54 patients, 10 (18.5%) achieved complete pathological response (pCR) and 21 (38.9%) achieved major pathological response (MPR). The post-NICT scan parameters and their changes were significantly associated with the pathological response. In addition, the values of the changes in the scanned parameters before and after treatment can further predict the pathological response of the patient., Conclusion: 18 F-FDG PET/CT is a useful tool to evaluate the efficacy of NICT and predict pathological response in patients with ESCC. The post-NICT scan parameters and their changes can help identify patients who are likely to achieve pCR or MPR., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Previous studies proposed that CYP1A2 rs762551 polymorphism might be associated with risk of lung cancer by influencing the function of CYP1A2. However, previous studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer reported inconsistent findings. We performed a meta-analysis of the published case-control studies to assess the association between CYP1A2 rs762551 polymorphism and risk of lung cancer. PubMed and Embase were searched to identify relevant studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer, and seven studies with a total of 3,320 subjects were finally included into the meta-analysis. The pooled odds ratio (OR) and 95 % confidence interval (95%CI) was calculated to evaluate the association. Meta-analysis of total studies showed that CYP1A2 rs762551 polymorphism contributed to risk of lung cancer under all four genetic models (C versus A: OR = 1.26, 95%CI 1.13 to 1.40, P < 0.001; CC versus AA: OR = 1.61, 95%CI 1.28 to 2.04, P < 0.001; CC versus AA/AC: OR = 1.52, 95%CI 1.11 to 2.09, P = 0.009; CC/AC versus AA: OR = 1.28, 95%CI 1.10 to 1.48, P = 0.001). Subgroup analysis based on ethnicity further suggested that CYP1A2 rs762551 polymorphism was associated with risk of lung cancer in Caucasians. These results from the meta-analysis suggest that CYP1A2 rs762551 polymorphism contributes to risk of lung cancer.

Background: The major reason for the poor prognosis of esophageal squamous cell carcinoma (ESCC) patients is lymph node (LN) metastases., Methodology/principal: In the present study, gene expression profiling assay (GEP) was performed to identify the differences in gene expression profiles between primary ESCC tumors that were with LN metastases (N(+)) and those without LN metastases (N(-))., Conclusions/significance: A total of 23 genes were identified as being significantly elevated, and 30 genes were sharply decreased in ESCC tumors that were N(+) compared with N- tumors. Among these genes, two transcripts of the short chain dehydrogenase/reductase family 9C, member 7 (SDR9C7) were observed 7 times more frequently in N(+) compared with N(-) tumors. Immunohistochemical staining showed that SDR9C7 expression closely correlated with metastasis, and would be a prognostic marker for ESCC patients. To investigate the role of SDR9C7 in the ESCC metastasis, repeated transwell assays were adopted to establish highly and non-invasive ESCC sublines, and western blot showed that SDR9C7 expression was markedly higher in highly invasive cells compared with non-invasive ones. Down-regulation of SDR9C7 dramatically inhibited the metastatic abilities in vitro and in vivo, and repressed the expression of MMP11 in highly invasive cells, indicating that SDR9C7 promotes ESCC metastasis partly through regulation of MMP11, and might be a potential prognostic and therapeutic marker for ESCC patients.

Twist-1 protein (also called Twist) has been suggested to be involved in tumor epithelial-mesenchymal transition (EMT) related progression, however, the mechanism by which twist promotes lymph node metastasis is not fully understood. In the present study, we found that nuclear twist expression is clearly correlated with lymph node (LN) metastasis as determined by immunohistochemistry (IHC). A highly invasive EC109 cell subline, EC109-P, was established by repeated in vitro transwell isolations for the cell model. Immunofluorescence (IF) assay demonstrated that nuclear twist expression was markedly higher in the highly invasive EC109-P cell line when compared with EC109 and EC9706 cells. Based on our cell model, the function and mechanism by which twist regulates LN metastasis in ESCC was investigated. The results showed that the overexpression of Twist could significantly increase the invasion and VEGF-C expression of EC9706 cells, whereas the knockdown of twist expression results in the opposite effects. This finding was further strengthened by the results of the analysis of co-expression of twist and VEGF-C by IHC in ESCC clinical samples. In summary, our study indicates that nuclear twist plays an important role in ESCC lymphatic metastasis by increasing the expression of VEGF-C. The combination of twist and VEGF-C detection could be a reliable prediction of LN metastasis in ESCC.

Traditional research modes aim to find cancer-specific single therapeutic target. Recently, emerging evidence suggested that some micro-RNAs (miRNA) can function as oncogenes or tumor suppressors. miRNAs are single-stranded, small noncoding RNA genes that can regulate hundreds of downstream target genes. In this study, we evaluated the miRNA expression patterns in gastric carcinoma and the specific role of miR-223 in gastric cancer metastasis. miRNA expression signature was first analyzed by real-time PCR on 10 paired gastric carcinomas and confirmed in another 20 paired gastric carcinoma tissues. With the 2-fold expression difference as a cutoff level, we identified 22 differential expressed mature miRNAs. Sixteen miRNAs were upregulated in gastric carcinoma, including miR-223, miR-21, miR-23b, miR-222, miR-25, miR-23a, miR-221, miR-107, miR-103, miR-99a, miR-100, miR-125b, miR-92, miR-146a, miR-214 and miR-191, and six miRNAs were downregulated in gastric carcinoma, including let-7a, miR-126, miR-210, miR-181b, miR-197, and miR-30aa-5p. After examining these miRNAs in several human gastric originated cell lines, we found that miR-223 is overexpressed only in metastatic gastric cancer cells and stimulated nonmetastatic gastric cancer cells migration and invasion. Mechanistically, miR-223, induced by the transcription factor Twist, posttranscriptionally downregulates EPB41L3 expression by directly targeting its 3'-untranslated regions. Significantly, overexpression of miR-223 in primary gastric carcinomas is associated with poor metastasis-free survival. These findings indicate a new regulatory mode, namely, specific miRNA, which is activated by its upstream transcription factor, could suppress its direct targets and lead to tumor invasion and metastasis., (©2011 AACR.)

Here, we have first investigated the roles of ZNRD1 in angiogenesis of leukaemia. The leukaemia cell line K562 was transfected with the vector that included the full-length cDNA of ZNRD1, then the growth and angiogenesis of cells were detected. Up-regulation of ZNRD1 could significantly inhibit the growth of cells, reduce tumour microvessel densities and inhibit the VEGF (vascular endothelial growth factor) production. The results of human miRNA array and real-time PCR showed that ZNRD1 could significantly up-regulate the expression of miR-214 and down-regulate the expression of miR-296. Taken together, ZNRD1 might inhibit tumour angiogenesis and could be considered as a target for leukaemia therapy.

Objective: We aimed first to investigate the expression pattern of miRNAs in esophageal squamous cell cancer and then compared it with those of adjacent benign esophageal tissues. The role of target miRNAs in the development of esophageal cancer was further detected., Summary Background Data: Although esophageal squamous cell carcinoma was of high incidence in China, the pathogenic mechanism remained largely unknown. A better understanding of changes in miRNA expression during esophageal carcinogenesis might lead to possible improvements in the diagnosis and treatment for esophageal carcinoma., Methods: The miRNAs were identified differentially expressed in esophageal cancer tissues, using miRNA microarray, real-time PCR, and Northern blot. The role of target miRNAs was investigated by in vitro and in vivo assay., Results: Nine miRNAs with increased expression and 3 with decreased expression were identified. The expression of miR-296 was found increasingly up-regulated in esophagitis tissues, esophageal carcinoma in situ, and esophageal squamous cell cancer tissues. Low expression of miR-296 was able to distinguish long-term survivors with node-positive disease from those dying within 20 months by predicting survival (median, 23.7 vs. 12.9 months). Downregulation of miR-296 might inhibit growth of esophageal cancer cells in vitro and in vivo through regulation of cyclin D1 and p27. Downregulation of miR-296 could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-nonrelated drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Downregulation of miR-296 could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of MDR1, but up-regulate the expression of Bax., Conclusions: MiR-296 might play important roles in the pathogenesis of esophageal cancer and considered as a potential target for this malignancy intervention.

We have efficiently generated the first monoclonal antibody against the cis-aconitic acid decarboxylase (CAD) protein, which is an enzyme of low stability. Hybridomas were screened by indirect enzyme-linked immunosorbent assay (ELISA) using either purified 6 x His-CAD fusion protein or purified 6 x His-ZNRD1 fusion protein as a control. One monoclonal antibody (MAb) named Z12 (IgG1), which is effective in detecting the recombinant and the cellular protein, was characterized by ELISA and Western immunoblotting. The CAD protein was also detected in gastric cancer and colon cancer tissues by immunohistochemical analysis. Thus, Z12 binds to native CAD protein and should be useful in studies of CAD protein function and expression.