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Background Unfolded protein response (UPR), an orchestrating adaptive mechanism activated by endoplasmic reticulum (ER) stress, plays an instrumental protumoral roles in several kinds of cancers, and high unfolded protein response is correlated to poorer prognosis and malignant hallmark. Considerable evidence indicates that UPR induced by oncogenic conditions is a distinguishing feature of cancer. Methods Bioinformatics mining was carried out by using the public pancer data of TCGA and other public databases to analyze the differential gene expression profiles of the patients and Cox regression analysis to find out the differentially expressed endoplasmic reticulum stress related genes with prognostic value. ER-stress Potential Index (EPI) was defined to computationally dissect the UPR trends via gene set enrichment analysis using R package ‘GSVA’. Combined with TCGA and GEO databases, the clinical characteristics of EPI were comprehensively analyzed in LIHC. Virtual screening was performed to find out potential compounds targeting STC2, which was a good diagnostic marker and pharmacological target towards endoplasmic reticulum stress in LIHC. Results Pan-cancer analysis results showed that unfolded protein response pathway was generally positive associated with poor prognosis of patients across different cancer types. It would be an important and ubiquitous mechanism in different tumors. High EPI was positive associated with tumor malignant phenotype, including higher death rate, recurrence rate, metastatic risk, larger tumor size and other undesirable aggressive clinical traits. In addition, EPI was also responsible for immune evasion via upregulating the expression of immunosuppressive gene and facilitating the production of pro-inflammatory and immunomodulatory cytokines. Besides, EPI played pivotal role in liver cancers’ resistance of chemotherapy and therapeutic targeting UPR would be enhance the anti-tumor effectiveness. STC2 would be a good diagnostic marker and pharmacological target in LIHC. Through virtual screening, we found that flavonoids compounds could be a good compound targeting STC2. Flavonoids could become a good pharmaceutical therapeutic candidate in unique or adjuvant therapeutic approaches toward LIHC. Conclusion EPI was associated with subtypes and clinical features and providing new insight into tumor biology and can guide efficient pharmalogical intervention of unfolded protein response to help patients.

Background. Anillin (ANLN), a ubiquitously expressed actin-binding protein, plays a critical tumor-promoting role in cell growth, migration, and cytokinesis. Numerous studies have suggested that ANLN is upregulated in many cancer types, as well as significantly associated with patient prognosis and malignant cancer characteristics. Herein, we performed an integrated pan-cancer analysis of ANLN and highlighted its underlying mechanism, which may benefit further exploration of the potential therapeutic options for cancer. Methods. ANLN expression data were extracted from online databases, including TCGA, GTEx, and CCLE databases. The TIMER database was used to study the association between ANLN expression with immune checkpoint genes and immunocyte infiltration. The ScanNeo pipeline was adopted for neoantigen discovery. KEGG analysis and the STRING tool were used to elucidate the potential mechanism of ANLN in cancer development. Results. ANLN is abnormally overexpressed in almost all cancer tissues compared with normal tissues. The high-ANLN expression level was positively associated with various malignant characteristics, suggesting its potential role in the immune microenvironment and poor prognosis. In addition, ANLN expression was correlated with the number of neoantigens and different phosphorylation pattern in various cancer types, revealing a functional role of genetic mutation accumulation and high phosphorylation in ANLN-mediated oncogenesis. Moreover, we found that ANLN was an important regulatory factor participating in many signaling events, especially the cell cycle and nucleocytoplasmic transport pathways. Conclusions. ANLN expression is generally overexpressed in various types of cancers, and it may have an important influence on tumor progression and development. ANLN expression is significantly associated with the immune checkpoint biomarkers and tumor immunity. Together, these findings suggest that ANLN may be a predictive marker for patient prognosis across cancers.

With the aim of enhancing the understanding of NEIL3 in prognosis prediction and therapy administration, we conducted a pan-cancer landscape analysis on NEIL3. The mutation characteristics, survival patterns, and immune features of NEIL3 across cancers were analyzed. Western blotting, qPCR, and immunohistochemistry were conducted to validate the bioinformatics results. The correlation between NEIL3 and chemotherapeutic drugs, as well as immunotherapies, was estimated. NEIL3 was identified as an oncogene with prognostic value in predicting clinical outcomes in multiple cancers. Combined with the neoantigen, tumor mutational burden (TMB), and microsatellite instability (MSI) results, a strong relationship between NEIL3 and the TME was observed. NEIL3 was demonstrated to be closely associated with multiple immune parameters, including infiltrating immunocytes and pro-inflammatory chemokines, which was verified by experiments. More importantly, patients with a higher expression of NEIL3 were revealed to be more sensitive to chemotherapeutic regimens and immune checkpoint inhibitors in selected cancers, implying that NEIL3 may be an indicator for therapeutic administration. Our study indicated NEIL3 has a strong association with the immune microenvironment and phenotypic changes in certain types of cancers, which facilitated the improved understanding of NEIL3 across cancers and highlighted the potential for clinical application of NEIL3 in precision medical stratification.

BACKGROUND AND AIM The thiopurines are effective in the management of patients with inflammatory bowel disease (IBD), but the association between thiopurines use and the risk of skin cancer (including nonmelanoma skin cancer [NMSC] and melanoma skin cancer) has already been sufficiently reported. However, the results of these studies are inconsistent, and thus, the objective of our analysis was to explore whether thiopurines can lead to an excess risk of skin cancer in IBD patients. METHODS MEDLINE, EMBASE, and the Cochrane Library were searched to identify relevant studies that evaluated the risk of skin cancer in IBD patients treated with thiopurines. A random effects meta-analysis was conducted to calculate the pooled incidence rate ratios as well as risk ratios (RRs). Subgroup analysis was performed to explore the potential source of heterogeneity. RESULTS Thirteen studies comprising 149 198 participants were included. The result suggested that thiopurines significantly increased the risk of overall skin cancer in IBD patients (random effects: RR = 1.80, 95% confidence interval [CI] 1.14-2.87, P = 0.013), among which NMSC showed an excess risk associated with thiopurines use (random effects: RR = 1.88, 95% CI 1.48-2.38, P

Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory receptor that is expressed on the surface of multiple immune cells and plays key roles in immune modulation. In patients with chronic hepatitis B (CHB), T cell number and functions are abnormal and the expression of inhibitory receptors is elevated. However, the expression of LAIR-1 on T cells in patients with CHB is still undetermined. We recruited 320 patients with CHB in different disease phases and 17 healthy donors. Serum biochemical and virological examinations were performed for each participant, and their demographic and clinical data were collected. According to the latest American Association for the Study of Liver Disease guidelines, we categorized the patients into 4 groups: immune active, immune tolerant, inactive CHB, and gray zone. Additionally, we tested the expression of LAIR-1 on T cells and T cell subsets using flow cytometry. We observed a significant decrease in LAIR-1 expression on CD3+ T cells and its two subsets (CD4+ and CD8+ T cells) in patients with CHB. LAIR-1 expression on T cells was the lowest in the immune active group. LAIR-1 expression levels on CD4+ and CD8+ T cells showed a significant negative association with hepatitis B virus (HBV) DNA load and were lower in hepatitis B e antigen (HBeAg)-positive patients than in HBeAg-negative patients (P

Background In the process of decreasing the morbidity of wound-related complications after vulvectomy and IL for treating vulvar malignancy, we performed a novel surgical procedure-single-incision radical vulvectomy (SIRV). Here, we share our initial experience and report its safety and feasibility. Methods Patients with advanced local vulvar tumors were sequentially enrolled in this prospective cohort study to undergo SIRV. While performing SIRV, routine radical vulvectomies were performed first. Subsequently, the flaps of the bridge area between the vulvectomy incisions and femoral triangles were separated and the lymph nodes underneath were removed. Anterior working spaces (AWS) before the femoral triangle were then made. The saphenous vein was carefully identified and retained, while the superficial and deep inguinal lymph nodes were removed from the medial to the lateral sides. After careful hemostasis, the wounds were sutured. Patient demographics, clinical data, pathologic data, operation time, node count, and complications were recorded. Results Ten patients underwent SIRV for vulvar cancer. Average hospital stay was 11.70±3.16 (range, 9-13) days. The average number of harvested lymph nodes was 7.59±3.62 (range, 3-15) and 15.14±3.63 (range, 11-20) for per side or both sides of the groin. Blood loss was ≤35 mL. Three patients developed inguinal lymphoceles and underwent needle aspirations. Two patients had impaired wound healing and achieved healing after dressing change. No other postoperative complications were noted during follow-up. Conclusions Compared with conventional open inguinal lymphadenectomy (COIL) and video endoscopic inguinal lymphadenectomy (VEIL), SIRV is a more minimally invasive procedure. Our short-term observations showed that SIRV is safe and feasible and has good future application prospects for vulvar cancer. However, definitive conclusions cannot be made. Therefore, long-term oncologic outcomes and large-scale clinical trials are warranted.

BACKGROUND AND AIMS The association between anti-tumour necrosis factor alpha agents and the risk of lymphoma in patients with inflammatory bowel disease has already been sufficiently reported. However, the results of these studies are inconsistent. Hence, this analysis was conducted to investigate whether anti-tumour necrosis factor alpha agents can increase the risk of lymphoma in inflammatory bowel disease patients. METHODS MEDLINE, EMBASE, and the Cochrane Library were searched to identify relevant studies which evaluated the risk of lymphoma in inflammatory bowel disease patients treated with anti-tumour necrosis factor alpha agents. A random-effects meta-analysis was performed to calculate the pooled incidence rate ratios as well as risk ratios. RESULTS Twelve studies comprising 285,811 participants were included. The result showed that there was no significantly increased risk of lymphoma between anti-tumour necrosis factor alpha agents exposed and anti-tumour necrosis factor alpha agents unexposed groups (random effects: incidence rate ratio [IRR] = 1.43, 95% CI, 0.91-2.25; P = 0.116; random effects: risk ratio [RR] = 0.83, 95% CI, 0.47-1.48; P = 0.534). However, monotherapy of anti-tumour necrosis factor alpha agents [random effects: IRR = 1.65, 95% CI, 1.16-2.35; P = 0.006; random effects: RR = 1.00, 95% CI, 0.39-2.59; P = 0.996] or combination therapy [random effects: IRR = 3.36, 95% CI, 2.23-5.05; P < 0.001; random effects: RR = 1.90, 95% CI, 0.66-5.44; P = 0.233] can significantly increase the risk of lymphoma. CONCLUSIONS Exposition of anti-tumour necrosis factor alpha agents in patients with inflammatory bowel disease is not associated with a higher risk of lymphoma. Combination therapy and anti-tumour necrosis factor alpha agents monotherapy can significantly increase the risk of lymphoma in patients with inflammatory bowel disease.

Supplemental Digital Content is available in the text, Background: The association between platelet count and the prognosis of patients with gastric cancer has already been reported by numerous studies. As the reports are inconsistent, we conducted this meta-analysis to evaluate the prognostic significance of platelet count in patients with gastric cancer. Methods: A comprehensive search was performed in PubMed, Embase, and the Cochrane Library to identify relevant studies, which evaluated the prognostic impact of pretreatment platelet count in patients with gastric cancer. Data was pooled using a random effect model to calculate hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). Results: Around 10 studies were included, comprising 8166 patients in total. The result showed that patients with thrombocytosis had significant worse overall survival (HR 1.57, 95% CI 1.36–1.81, P