MAGUK p55 subfamily member 7, a part of the membrane palmitoylated protein subfamily, is an essential adapter that promotes epithelial cell polarity and has increasing significance in multiple cancers, including esophageal cancer, clear cell renal cell carcinoma, breast cancer, and pancreatic ductal adenocarcinoma. This paper aims to determine the effect of the MAGUK p55 subfamily member 7 in various tumor types using The Cancer Genome Atlas and Genotype-Tissue Expression database. A variety of software and web platforms, such as cBioPortal, GEPIA2, TIMER2, UALCAN, R, STRING, and DAVID, were used to obtain and analyze data. Notably, low expression of MAGUK p55 subfamily member 7 was observed in most cancers. In addition, low expression of MAGUK p55 subfamily member 7 predicted poor prognoses in cancer patients. Mutation was the most frequent genetic alteration type in MAGUK p55 subfamily member 7, with the phosphorylation sites identified as S412 and S490 in various cancers. Furthermore, expression of MAGUK p55 subfamily member 7 was associated with cancer-related fibroblasts and CD8+ T cells. Gene enrichment analysis indicated that MAGUK p55 subfamily member 7 influences cancer through the Rap1 signaling pathway. This paper elucidates the biological significance of MAGUK p55 subfamily member 7 in human pan-cancer prognosis and immune response.

BACKGROUND: Observational study investigated the association between pernicious anemia (PA) and cancers. However, with the exception of gastric cancer, the results are mostly contradictory. The purpose of this study was to investigate the potential causal relationship between PA and cancers through bidirectional two-sample Mendelian randomized (MR) analysis.
METHODS: The European sample FinnGen project provided the genetic summary data for PA and 20 site-specific cancers. This bidirectional two-sample MR design mainly used the inverse variance weighting (IVW) method to evaluate the causal relationship between PA and cancer risk. Benjamini-Hochberg correction was performed to reduce the bias caused by multiple tests.
RESULTS: Our study shows that there was a causal relationship between PA and gastric cancer, prostate cancer, testicular cancer and malignant melanoma of skin, and there was a reverse causal relationship between prostate cancer or gastric cancer and PA (P < 0.05). After Benjamini-Hochberg correction test, there was still a causal correlation between PA and gastric or prostate cancer (P\' < 0.05), while there was only an implied causal association between PA and testicular cancer and malignant melanoma of skin (P\'> 0.05). There was still a reverse causal relationship between gastric cancer and PA (P\'< 0.05), while prostate cancer shows an implied reverse causal relationship(P\'> 0.05). In addition, MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy.
CONCLUSIONS: PA may be genetically associated with testicular cancer, prostate cancer, gastric cancer, and malignant melanoma of skin.

To use a nomogram to predict the risk of mortality and estimate the impact of current treatment on the prognosis of glioma patients.
A total of 3798 cases were obtained from the Surveillance Epidemiology and End Results database according to the selection criteria. A nomogram was built on the independent clinical factors screened by the variance inflation factor, univariate analyses and a multivariate Cox regression model. Then, categorising the overall population into high-risk, medium-risk and low-risk groups using nomogram-derived risk scores, to study the impact of treatment on different subgroups\' survival outcomes. Furthermore, based on the postmatch cohorts, the influences of treatment on survival outcomes were assessed by the log-rank test.
Age, race, stage of disease, histological type, histological grade, surgery, radiotherapy and chemotherapy were identified as the independent prognostic factors. A nomogram with good discrimination and consistency was built. Generally, the patients who underwent surgery, radiotherapy and chemotherapy were more likely to achieve better prognosis than those who did not, except for those who received radiotherapy in the low-risk cohort and those who underwent surgery in the high-risk cohort. Furthermore, the isocitrate dehydrogenase 1/2 (IDH1/2) wild-type patients with surgery, radiotherapy or chemotherapy tended to have higher survival probabilities, while some inconsistent results were observed in the IDH mutant-type cohort.
Surgery, radiotherapy and chemotherapy improved the prognosis, while appropriate selection of topical treatment for the low-risk or high-risk patients deserves further consideration. IDH status gene might be a reliable indicator of therapeutic effectiveness.

Trisomy karyotype occurs in 5%-10% of AML. Its mutational landscape and prognostic significance are not well defined. A cohort of 156 trisomy AML patients was analysed, with reference to 615 cytogenetically normal (CN) AML patients. Trisomy AML showed distinct mutational landscape with more prevalent SMC1A, N/KRAS, ASXL1 and BCOR but fewer CEBPAbZIP and NPM1 mutations in patients ≤60, and fewer NPM1 mutations in those >60. NRAS mutations were associated with poor outcome in trisomy AML, whereas DNMT3A and FLT3-ITD mutations had neutral effect. Trisomy AML appeared biologically distinct from CN-AML.

BACKGROUND: Hitherto, the association of vitamin D intake and digestive system cancers occurrence still causes disputation among the researchers. This study aimed to investigate the genetic relation between vitamin D ingestion and digestive system cancers (which are esophageal, gastric, hepatic, pancreatic, and colorectal cancers) by a two-sample Mendelian randomization (MR) analysis, using datasets derived from IEU OpenGWAS database.
METHODS: This study is based on a genome-wide association study (GWAS) for vitamin D and digestive system cancers, with a sample amount ranging from 218,792 to 496,946 European ancestry individuals. The study first investigated the causal relationship between vitamin D and each digestive system cancers using inverse-variance weighting (IVW), weighted medians, and MR-Egger regression and then used meta-analysis to summarize the IVW results for the different cancers. We also performed additional sensitivity tests to assess the validity of the results.
RESULTS: In this study, we screened out 117 SNPs as potential instrumental variables for 25(OH)D and identified 101 fixed SNPs as instrumental variables for digestive system cancers. The results of the IVW failed to reveal any causal relationship between the genetically predisposed vitamin D level and the risk of digestive system cancers (esophageal cancer p = 0.400, OR = 1.397, 95% CI 0.642-3.040; gastric cancer p = 0.796, OR = 0.939, 95% CI 0.585-1.510; hepatic cancer p = 0.347, OR = 1.445, 95% CI 0.671-3.109; pancreatic cancer p = 0.905, OR = 0.969, 95% CI 0.581-1.618; colorectal cancer p = 0.127, OR = 0.0.841, 95% CI 0.673-1.051). The pooled ORs (odds ratio) are 0.918 (95% CI 0.770-1.097, p = 0.348).
CONCLUSIONS: There is no causal relationship between vitamin D and the occurrence of digestive system cancers. The risk of digestive system cancers cannot be alleviated by merely increasing vitamin D intake.

BACKGROUND: Centrosomal protein 55 (CEP55) plays a significant role in specific cancers. However, comprehensive research on CEP55 is lacking in pan-cancer.
METHODS: In-house and multi-center samples (n = 15,823) were used to analyze CEP55 in 33 cancers. The variance of CEP55 expression levels among tumor and control groups was evaluated by the Wilcoxon rank-sum test and standardized mean difference (SMD). The clinical value of CEP55 in cancers was assessed using receiver operating characteristic (ROC) curves, Cox regression analysis, and Kaplan-Meier curves. The correlations between CEP55 expression and the immune microenvironment were explored using Spearman\'s correlation coefficient.
RESULTS: The data of clustered regularly interspaced short palindromic repeats confirmed that CEP55 was essential for the survival of cancer cells in multiple cancer types. Elevated CEP55 mRNA expression was observed in 20 cancers, including glioblastoma multiforme (p < 0.05). CEP55 mRNA expression made it feasible to distinguish 21 cancer types between cancer specimens and their control samples (AUC = 0.97), indicating the potential of CEP55 for predicting cancer status. Overexpression of CEP55 was correlated with the prognosis of cancer individuals for 18 cancer types, exhibiting its prognostic value. CEP55 expression was relevant to tumor mutation burden, microsatellite instability, neoantigen counts, and the immune microenvironment in various cancers (p < 0.05). The expression level and clinical relevance of CEP55 in cancers were verified in lung squamous cell carcinoma using in-house and multi-center samples (SMD = 4.07; AUC > 0.95; p < 0.05).
CONCLUSIONS: CEP55 may be an immune-related predictive and prognostic marker for multiple cancers, including lung squamous cell carcinoma.

Gallbladder cancer (GBC) is an aggressive type of digestive system cancer with a dismal outcome. Given the lack of effective treatment options, the disease rapidly reoccurs and 5-year survival rate is <5%. Our team previously found that a significant percentage of GBC tissues harboured mutations of the ErbB-related pathway. Afatinib is a chemically synthesised drug specifically targeting the ErbB pathway mutations. However, its efficacy in the treatment of patients with GBC remains unknown. Circulating tumour DNA (ctDNA) refers to a proportion of cell-free DNA in the blood which is released by apoptotic and necrotic cells from tumours in situ, metastatic foci or circulating tumour cells. ctDNA-based liquid biopsy is a non-invasive pathological detection method that offers additional value to evaluate the therapeutic efficacy of antitumour drugs.
We conduct a multicentre and randomised study on afatinib combined with gemcitabine and oxaliplatin (GEMOX) in patients with ErbB pathway mutated GBC. Clinical and biological evaluation involving ErbB pathway ctDNA detection will be made during the 3-year follow-up after participation. The primary objective of this clinical trial is to evaluate the clinical efficacy of afatinib. Disease-free survival is the primary end point and will be correlated with plasma ctDNA of patients in the treatment with afatinib. In addition, we will evaluate the sensitivity and specificity of plasma ctDNA for monitoring tumour recurrence and progression. Finally, we will assess the safety of afatinib by keeping an eye on the safety indicators.
The study was approved by the medical-ethical review committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. The clinical trials results, even inconclusive, will be published in peer-reviewed journals.
NCT04183712.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumour with limited treatment options. Here, we identified syndecan binding protein (SDCBP), also known as syntenin1, as a novel targetable factor in promoting PDAC tumour progression. We also explored a therapeutic strategy for suppressing SDCBP expression.
We used samples from patients with PDAC, human organoid models, LSL-KrasG12D/+mice, LSL-Trp53R172H/+ and Pdx1-Cre (KPC) mouse models, and PDX mouse models. Immunostaining, colony formation assay, ethynyl-2-deoxyuridine incorporation assay, real-time cell analysis, cell apoptosis assay, automated cell tracking, invadopodia detection and gelatin degradation assays, coimmunoprecipitation, and pull-down assays were performed in this study.
The median overall survival and recurrence-free survival rates in the high-SDCBP group were significantly shorter than those in the low-SDCBP group. In vitro and in vivo studies have demonstrated that SDCBP promotes PDAC proliferation and metastasis. Mechanically, SDCBP inhibits CK1δ/ε-mediated YAP-S384/S387 phosphorylation, which further suppresses β-TrCP-mediated YAP1 ubiquitination and proteasome degradation by directly interacting with YAP1. SDCBP interacts with the TAD domain of YAP1, mainly through its PDZ1 domain. Preclinical KPC mouse cohorts demonstrated that zinc pyrithione (ZnPT) suppresses PDAC tumour progression by suppressing SDCBP.
SDCBP promotes the proliferation and metastasis of PDAC by preventing YAP1 from β-TrCP-mediated proteasomal degradation. Therefore, ZnPT could be a promising therapeutic strategy to inhibit PDAC progression by suppressing SDCBP.

Chemotherapy is widely used to treat patients with cancer. However, resistance to chemotherapeutic drugs remains a major clinical concern. The mechanisms of cancer drug resistance are extremely complex and involve such factors such as genomic instability, DNA repair, and chromothripsis. A recently emerging area of interest is extrachromosomal circular DNA (eccDNA), which forms owing to genomic instability and chromothripsis. eccDNA exists widely in physiologically healthy individuals but also arises during tumorigenesis and/or treatment as a drug resistance mechanism. In this review, we summarize the recent progress in research regarding the role of eccDNA in the development of cancer drug resistance as well as the mechanisms thereof. Furthermore, we discuss the clinical applications of eccDNA and propose some novel strategies for characterizing drug-resistant biomarkers and developing potential targeted cancer therapies.

To evaluate the risk factors and construct a nomogram model for the prognosis of primary liver cancer in the elderly based on the data from the US SEER database.
The latest data of patients with primary liver cancer were extracted from the SEER database using SEER*STAT software, and the required variables were included. The data were screened and then divided into a training cohort and a validation cohort. A nomogram model was constructed by screening the variables through univariate and multivariate Cox analysis. The C-Index, ROC and calibration curves were used for model evaluation.
A total of 10 824 eligible cases from 2004 to 2017 were extracted, among which, 7757 cases were included in the training cohort and 3247 in the validation cohort. The C-Index of the model was 0.747 (in the training cohort) and 0.773 (in the validation cohort). The 3-year area under the curve (AUCs) of the training and the validation cohorts were 0.760 and 0.750, and the 5-year AUCs of the two cohorts were 0.761 and 0.748. The calibration curves showed an ideal calibration of the constructed model.
The nomogram model constructed followed by Cox regression analysis showed moderate calibration and discrimination property, and can provide reference to a certain extent for furture clinical application of primary liver cancer in the elderly.