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Background: Plakophilin 2 gene (PKP2) has been revealed to be differentially expressed in various cancer types and is correlated with prognosis. However, the role of PKP2 in colon adenocarcinoma remains indistinct., Methods: Differences in transcriptional expression of PKP2 between colon adenocarcinoma tissues and normal adjacent tissues were acquired from the publicly available dataset-the Cancer Genome Atlas. A receiver operating curve (ROC) was constructed to differentiate colon adenocarcinoma tissues from adjacent normal tissues. The Kaplan-Meier plot method was performed to evaluate the effect of PKP2 on survival. The correlation between mRNA expression of PKP2 and immune infiltrating was determined by the Tumor Immune Estimation Resource and Tumor-Immune System Interaction databases., Results: The expression of PKP2 in colon adenocarcinoma tissues was significantly downregulated compared with corresponding adjacent normal tissues. Decreased PKP2 mRNA expression was associated with lymph node metastases and advanced pathological stage. The ROC curve analysis indicated that with a cutoff value of 6.034, the sensitivity and specificity for PKP2 differentiating the colon adenocarcinoma tissues from the adjacent normal tissues were 90.2 and 66.5% respectively. Kaplan-Meier plot survival analysis revealed that colon adenocarcinoma patients with low-PKP2 had a worse prognosis than those with high-PKP2 (68.2 vs. 101.4 months, p = 0.028). Correlation analysis showed that mRNA expression of PKP2 was correlative with immune infiltrates., Conclusions: Downregulated PKP2 is significantly correlated with unfavorable immune infiltrating and survival in colon adenocarcinoma. This research indicates that PKP2 can be selected as a novel biomarker of potential immunotherapy targets and unfavorable prognosis in colon adenocarcinoma., (© 2023 The Authors. The Journal of Gene Medicine published by John Wiley & Sons Ltd.)

Backgrounds: The clinicopathologic features and biological behaviors of pancreatic mixed adenoneuroendocrine carcinoma (pMANEC) and its impacts on survival are poorly known., Methods: We retrospectively reviewed seven pMANEC cases from a single institution from September 2010 to January 2017 along with twenty-one previously reported cases from the literature. Survival and prognostic analyses were conducted using Kaplan-Meier estimates and Cox regression, respectively., Results: Seven pMANEC cases were identified during the study interval. Among the six patients who underwent operations, five reached R0 resections, one experienced postoperative pancreatic fistula, and two suffered other complications. The median progression-free survival (PFS) and disease-specific survival (DSS) were 7.5 months (2 to 36 months) and 15 months (6 to 36 months), respectively. A total analysis of twenty-eight pMANEC cases showed that patients were mostly older (median age, 59.5 years) and male (64.3%). The two most common symptoms were abdominal pain (53.6%) and obstructive jaundice (35.7%). The majority of pMANECs were non-functional (89.3%) and located in the pancreatic head (64.3%). The median diameter of pMANEC was 3.0 cm, with a wide range (0.5 to 19.0 cm). Lymph node metastasis (P = 0.015) was associated with decreased DSS, while age (P = 0.414), sex (P = 0.125), tumor size (P = 0.392), location (P = 0.913), functional status (P = 0.313), CA19-9 level (P = 0.608), and liver metastasis (P = 0.935) did not show significant prognoses on DSS., Conclusions: We reported seven pMANEC cases and outlined their clinical behaviors and prognoses with a review of twenty-one cases from the literature. Lymph node metastasis was found to be a negative prognostic factor of DSS based on the present study.

Esophageal cancer (EC) is one of the most common cancers in China. The purpose of this study was to investigate the updated incidence rates and risk factors of EC in Nan'ao Island, where the EC incidence rate was chronically the highest in southern China. To calculate the annual incidence rate, data on 338 EC cases from Nan'ao Cancer Registry system diagnosed during 2005-2011 were collected. A case-control study was conducted to explore the EC risk factors. One hundred twenty-five alive EC patients diagnosed during 2005-2011 and 250 controls were enrolled into the case-control study. A pre-test questionnaire on demography, dietary factors, drinking water treatment, and behavioral factors was applied to collect information of all participants. The average EC incidence rates during 2005-2011 were 66.09/105, 94.62/105, 36.83/105 for both genders, males and females, respectively, in Nan'ao Island. The EC incidence rate in males was 2.40- to 4.55-fold higher than that in females in the period from 2006 to 2011 (P < 0.05). Considering the onset age, males tend to be much younger than females and reached peak incidence rate at a younger age (P < 0.05). Drinking water treatment by filter (odds ratio [OR] = 0.28, 95% confidence interval [95% CI] = 0.13-0.58) and fruit consumption (OR = 0.55, 95% CI = 0.32-0.94) reduced the risk for EC. On the contrary, the pickled vegetables consumption (OR = 2.64, 95% CI = 1.46-4.76) and liquor drinking (OR = 2.32, 95% CI = 1.21-4.44) increased the risk for EC. These results may be of importance for future research on EC etiology and prevention strategies., (© 2016 International Society for Diseases of the Esophagus.)

BPTF, a subunit of NURF, is well known to be involved in the development of eukaryotic cell, but little is known about its roles in cancers, especially in non-small-cell lung cancer (NSCLC). Here we showed that BPTF was specifically overexpressed in NSCLC cell lines and lung adenocarcinoma tissues. Knockdown of BPTF by siRNA significantly inhibited cell proliferation, induced cell apoptosis and arrested cell cycle progress from G1 to S phase. We also found that BPTF knockdown downregulated the expression of the phosphorylated Erk1/2, PI3K and Akt proteins and induced the cleavage of caspase-8, caspase-7 and PARP proteins, thereby inhibiting the MAPK and PI3K/AKT signaling and activating apoptotic pathway. BPTF knockdown by siRNA also upregulated the cell cycle inhibitors such as p21 and p18 but inhibited the expression of cyclin D, phospho-Rb and phospho-cdc2 in lung cancer cells. Moreover, BPTF knockdown by its specific shRNA inhibited lung cancer growth in vivo in the xenografts of A549 cells accompanied by the suppression of VEGF, p-Erk and p-Akt expression. Immunohistochemical assay for tumor tissue microarrays of lung tumor tissues showed that BPTF overexpression predicted a poor prognosis in the patients with lung adenocarcinomas. Therefore, our data indicate that BPTF plays an essential role in cell growth and survival by targeting multiply signaling pathways in human lung cancers.

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer.

Upregulated expression and activation of human telomerase reverse transcriptase (hTERT) is a hallmarker of lung tumorigenesis. However, the mechanism underlying the aberrant hTERT activity in lung cancer cells remains poorly understood. In this study, we found the transcriptional co-activator CBP as a new hTERT promoter-binding protein that regulated hTERT expression and tumor growth in lung adenocarcinoma cells using a biotin-streptavidin-bead pulldown technique. Chromatin immunoprecipitation assay verified the immortalized cell and tumor cell-specific binding of CBP on hTERT promoter. Overexpression of exogenous CBP upregulated the expression of the hTERT promoter-driven luciferase and endogenous hTERT protein in lung cancer cells. Conversely, inhibition of CBP by CBP-specific siRNA or its chemical inhibitor repressed the expression of hTERT promoter-driven luciferase and endogenous hTERT protein as well as telomerase activity. Moreover, inhibition of CBP expression or activity also significantly reduced the proliferation of lung cancer cells in vitro and tumor growth in an xenograft mouse model in vivo. Immunohistochemical analysis of tissue microarrays of lung cancers revealed a positive correlation between CBP and hTERT. Importantly, the patients with high CBP and hTERT expression had a significantly shorter overall survival. Furthermore, CBP was found to interact with and acetylate transactivator Sp1 in lung cancer cells. Inhibition of CBP by CBP-specific siRNA or its chemical inhibitor significantly inhibited Sp1 acetylation and its binding to the hTERT promoter. Collectively, our results indicate that CBP contributes to the upregulation of hTERT expression and tumor growth, and overexpression of CBP predicts poor prognosis in human lung cancers.

Introduction: Thyroid transcription factor-1 (TTF1) plays a role in lung adenocarcinoma development. We investigated the significance of TTF1 in primary lung adenocarcinomas, lymph node metastases, and malignant pleural effusions (MPEs)., Methods: We studied TTF1 in 175 primary lung adenocarcinomas, 52 lymph node metastases, and 46 MPE using microarray-based fluorescence in situ hybridization, immunohistochemistry, and messenger RNA (mRNA) in situ hybridization. Real-time reverse transcription polymerase chain reaction was used to investigate correlations between TTF1 amplification and mRNA expression. Correlations between clinicopathologic characteristics, TTF1 amplification, TTF1 expressions, overall survival, and prognosis were analyzed., Results: TTF1 was amplified in 7% of primary lung adenocarcinomas, 4% of lymph node metastases, and 4% of MPE. TTF1 amplification in lung adenocarcinomas was associated with pathologic subtypes (p = 0.029). Patients with positive TTF1 protein and mRNA expressions had improved overall survival if TTF1 was unamplified compared with those with TTF1 amplification (p = 0.068). A multivariate model did not show patients with positive TTF1 expressions tended to have better prognoses if TTF1 was unamplified compared with those with TTF1 amplification (p = 0.068). Survival time was longer for patients with TTF1 expressions in both primary lung tissues (p < 0.001) and MPE (p = 0.045). A multivariate model confirmed the prognostic value of TTF1 expressions in lung adenocarcinoma (p < 0.001). A multivariate model confirmed the prognostic value of TTF1 expressions in lung adenocarcinoma tissues (p < 0.001) while not in MPE (p = 0.058). TTF1 mRNA level was higher in cases with TTF1 amplification compared with those without TTF1 amplification., Conclusions: Patients with lung adenocarcinoma without TTF1 amplification tend to have better prognoses than those with TTF1 amplification in cases with positive TTF1 expressions. Positive TTF1 expressions in lung adenocarcinoma tissues are favorable prognostic parameters in patients with lung adenocarcinoma.

The mortality caused by cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) ranks second among female malignant tumour deaths, but their diagnostic and therapeutic targets are still limited. N6‐methyladenosine (m6A) is the most common and extensive modification in mRNA molecules, and its methylation regulators participate in regulating the occurrence and development of many tumours. However, whether m6A RNA methylation regulators can be used as independent prognostic indicators of CESC remains unknown. This study unveiled differential expression of 20 m6A RNA methylation regulators between normal and CESC tumour samples, which RNA sequence data and clinical information were obtained from TCGA database. As a result, five m6A RNA methylation regulators (FTO, HNRNPA2B1, RBM15, IGF2BP1, IGF2BP3) were identified to be significantly linked to CESC tumour status. After Lasso cox regression analysis, six m6A RNA methylation regulators (YTHDC2, YTHDC1, ALKBH5, ZC3H13, RBMX, YTHDF1) were chosen to construct a risk signature. CESC patients were then classified as high‐risk and low‐risk group based on the median risk score. The overall survival (OS) of the CESC patients in high‐risk group was significantly lower than that in low‐risk group, and the area under curve (AUC) is 0.718. Moreover, the risk model can be an independent prognosis factors for CESC patients and can predict OS of CESC patients with different clinical factors. In conclusion, m6A RNA methylation regulators are closely correlated with CESC clinical characteristics and the selected six m6A RNA methylation regulators may be useful for CESC patients personalized treatment. [ABSTRACT FROM AUTHOR]

Purpose: To develop a predictive model by 18F-FDG PET/CT radiomic features and to validate the predictive value of the model for distinguishing solitary lung adenocarcinoma from tuberculosis. Methods: A total of 235 18F-FDG PET/CT patients with pathologically or follow-up confirmed lung adenocarcinoma (n = 131) or tuberculosis (n = 104) were retrospectively and randomly divided into a training (n = 163) and validation (n = 72) cohort. Based on the Transparent Reporting of Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD), this work was belonged to TRIPOD type 2a study. The Mann-Whitney U test and least absolute shrinkage and selection operator (LASSO) algorithm were used to select the optimal predictors from 92 radiomic features that were extracted from PET/CT, and the optimal predictors were used to build the radiomic model in the training cohort. The meaningful clinical variables comprised the clinical model, and the combination of the radiomic model and clinical model was a complex model. The performances of the models were assessed by the area under the receiver operating characteristic curve (AUC) in the training and validation cohorts. Results: In the training cohort, 9 radiomic features were selected as optimal predictors to build the radiomic model. The AUC of the radiomic model was significantly higher than that of the clinical model in the training cohort (0.861 versus 0.686, p < 0.01), and this was similar in the validation cohort (0.889 versus 0.644, p < 0.01). The AUC of the radiomic model was slightly lower than that of the complex model in the training cohort (0.861 versus 0.884, p > 0.05) and validation cohort (0.889 versus 0.909, p > 0.05), but there was no significant difference. Conclusion: 18F-FDG PET/CT radiomic features have a significant value in differentiating solitary lung adenocarcinoma from tuberculosis. [ABSTRACT FROM AUTHOR]