Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

N6-methyladenosine (m6A) is a dynamic, reversible post-transcriptional modification, and the most common internal modification of eukaryotic messenger RNA (mRNA). Considerable evidence now shows that m6A alters gene expression, thereby regulating cell self-renewal, differentiation, invasion, and apoptotic processes. M6A methylation disorders are directly related to abnormal RNA metabolism, which may lead to tumor formation. M6A methyltransferase is the dominant catalyst during m6A modification; it removes m6A demethylase, promotes recognition by m6A binding proteins, and regulates mRNA metabolic processes. Bladder cancer (BC) is a urinary system malignant tumor, with complex etiology and high incidence rates. A well-differentiated or moderately differentiated pathological type at initial diagnosis accounts for most patients with BC. For differentiated superficial bladder urothelial carcinoma, the prognosis is normally good after surgery. However, due to poor epithelial cell differentiation, BC urothelial cell proliferation and infiltration may lead to invasive or metastatic BC, which lowers the 5-years survival rate and significantly affects clinical treatments in elderly patients. Here, we review the latest progress in m6A RNA methylation research and investigate its regulation on BC occurrence and development.

Immunologic constant of rejection signature is prognostic in soft-tissue sarcoma and refines the CINSARC signature

BackgroundSoft-tissue sarcomas (STSs) are heterogeneous and aggressive tumors, with high metastatic risk. The immunologic constant of rejection (ICR) 20-gene signature is a signature of cytotoxic immune response. We hypothesized that ICR might improve the prognostic assessment of early-stage STS.MethodsWe retrospectively applied ICR to 1455 non-metastatic STS and searched for correlations between ICR classes and clinicopathological and biological variables, including metastasis-free survival (MFS).ResultsThirty-four per cent of tumors were classified as ICR1, 27% ICR2, 24% ICR3, and 15% ICR4. These classes were associated with patients’ age, pathological type, and tumor depth, and an enrichment from ICR1 to ICR4 of quantitative/qualitative scores of immune response. ICR1 class was associated with a 59% increased risk of metastatic relapse when compared with ICR2-4 class. In multivariate analysis, ICR classification remained associated with MFS, as well as pathological type and Complexity Index in Sarcomas (CINSARC) classification, suggesting independent prognostic value. A prognostic clinicogenomic model, including the three variables, was built in a learning set (n=339) and validated in an independent set (n=339), showing greater prognostic precision than each variable alone or in doublet. Finally, connectivity mapping analysis identified drug classes potentially able to reverse the expression profile of poor-prognosis tumors, such as chemotherapy and targeted therapies.ConclusionICR signature is independently associated with postoperative MFS in early-stage STS, independently from other prognostic features, including CINSARC. We built a robust prognostic clinicogenomic model integrating ICR, CINSARC, and pathological type, and suggested differential vulnerability of each prognostic group to different systemic therapies.

Study on PD-L1 Expression in NSCLC Patients and Related Influencing Factors in the Real World

PD-L1 is one of the current biomarkers for immune checkpoint inhibitor (ICI) therapy in patients with non-small-cell lung cancer. However, the expression of PD-L1 in the real world and its related influencing factors remain unclear. We want to observe the expression of PD-L1 in the real world and study the related influencing factors through the collection and analysis of clinical data. R software (version 4.0) was used to perform data analysis and the “corplot” package for correlation analysis. A total of 296 individuals (mean [SD] age, 67 [9] years; 23%female) were assessed. According to the expression amount of PD-L1, the cohort was divided into low nonexpression group ( PD ‐ L 1 < 1 % , 26.7%), low-expression group ( 1 % ≤ PD ‐ L 1 < 50 % , 49.3%), and high-expression group ( PD ‐ L 1 ≥ 50 % , 23.5%). Age, gender, underlying diseases, smoking status, and PD-L1 expression level were not statistically significant. We found that the expression of PD-L1 was correlated with serum albumin ( P < 0.05 ) and pathological type ( P < 0.05 ) and had a negative correlation with EGFR mutation but did not correlate with gender, age, smoking status, combined with underlying diseases, tumor stage, whether it was initially treated or not, sampling site, specimen type, specimen storage time, R-IFN, CD4, CD8, NLR, CRP, and LDH. The present findings indicated that serum albumin, pathological type, and EGFR mutations are associated with PD-L1 expression in patients with NSCLC, which may provide a new basis for individualized immunotherapy and need further study to confirm. The results of this study help to further reveal the actual expression of PD-L1 in non-small-cell lung cancer patients with real events.

Factors influencing recurrence after complete remission in children with hepatoblastoma: A 14-year retrospective study in China

Objective After a complete remission to treatment for hepatoblastoma, some children still have recurrence. We identified and explored the factors that influence recurrence after complete remission in a retrospective study. Methods Of 197 children with hepatoblastoma, 140 (71.1%) achieved initial complete remission and were enrolled in factor analysis. Variables consisted of age, sex, PRE-Treatment EXTent of tumor (PRETEXT) stage, pathologic type, metastatic disease, serum alpha-fetoprotein level, vascular involvement, and surgical margin status. We employed univariate and multivariate analyses to assess the relationship between each factor and tumor recurrence. Results Of 140 children who achieved initial complete remission, 42 (30%) had recurrent hepatoblastoma. The 5-year overall survival rates for the non-recurrence and recurrence group were 99.0% and 78.6%, respectively. The overall 1-year, 3-year, and 5-year recurrence-free survival (RFS) rates were 77.8%, 69.8%, and 69.8%, respectively. All recurrences occurred within 2 years from complete remission. The RFS rate was significantly higher in children younger than 3 years and in those with mixed pathological type, PRETEXT II and III, without metastatic disease, without vascular involvement, and microscopic negative margin than in that of children older than 3 years, with epithelial pathological type, PRETEXT IV, metastatic disease, vascular involvement, and macroscopic positive margin (P < 0.001, = 0.020, < 0.001, = 0.004, = 0.002, and < 0.001, respectively). The independent risk factors for recurrence after complete remission were age ≥3 years, PRETEXT IV, and metastatic disease (P < 0.05). Conclusion Age, PRETEXT stage, metastatic disease, vascular involvement, pathologic type, and surgical margin status might be associated with recurrent hepatoblastoma after complete remission; meanwhile, age ≥3 years, PRETEXT IV, and metastatic disease are independent risk factors of recurrence. Further research is needed on the causes of tumor recurrence, which may improve the long-term outcomes of children with hepatoblastoma.

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Positive Patient With Refractory Metastatic Thyroid Hürthle Cell Carcinoma: A Case Report and Literature Review

Thyroid Hürthle cell carcinoma, known as thyroid eosinophilic carcinoma, is a rare pathological type of differentiated thyroid cancer (DTC), representing 3-4% of all thyroid cancers. However, given the high risk of invasion and metastasis, thyroid Hürthle cell carcinoma has a relatively poor prognosis. Traditional treatment methods have limited effects on patients with metastatic thyroid cancers. Developing a valuable therapy for advanced thyroid carcinomas is an unfilled need, and immunotherapy could represent another choice for these tumors. We herein reported the case of a patient with recurrent advanced thyroid Hürthle cell cancer and positive programmed death-ligand 1 (PD-L1) expression, who suffered tumor progression after re-surgery, radiotherapy, and targeted therapy. It is encouraging that PD-1 inhibitors in combination with GM-CSF and stereotactic body irradiation (SBRT) on metastatic disease have a significant anti-tumor effect.

HER2 and p53 Expression in Marjolin’s Ulcer

Background：Marjolin's ulcer is a malignant tumor that is different from other skin ulcers, and its pathogenesis is not yet clear. The diagnosis and prognosis of Marjolin's ulcer lack valuable marks on immunohistochemistry (IHC).Methods: In this study, we detected the expression of HER2 and p53 in Majorlin’s ulcer with immunohistochemistry, and retrospectively analyze the clinicopathological characteristics of Marjolin's ulcer samples.Results: Our results showed that no HER2 but p53 was detected in Majorlin’s Ulcer samples. Meanwhile, by statistic analysis we found that the positive expression rate of p53 in Majorlin’s Ulcer samples was associated with sex, course of disease, ulcer size, pathological type of ulcer canceration, and degree of tumor differentiation. Furthermore, we showed that the positive rate of p53 was proportional to the malignancy degree of Marjolin’s ulcer. Conclusions:Our results of this study will lay a foundation for diagnosis of Marjolin's ulcer and even prevention of Marjolin's ulcer progression

Clinical Significance of CYFRA21-1, AFP, CA-153, CEA, and CA-199 in the Diagnosis of Lung Cancer Ocular Metastasis in Hypertension Population

Purpose: To detect lung metastases, we conducted a retrospective study to improve patient prognosis.Methods: Hypertension patients with ocular metastases (OM group; n = 58) and without metastases (NM group; n = 1,217) were selected from individuals with lung cancer admitted to our hospital from April 2005 to October 2019. The clinical characteristics were compared by Student's t-test and chi-square test. Independent risk factors were identified by binary logistic regression, and their diagnostic value evaluated by receiver operating characteristic curve analysis.Results: Age and sex did not differ significantly between OM and NM groups; There were significant differences in pathological type and treatment. Adenocarcinoma was the main pathological type in the OM group (67.24%), while squamous cell carcinoma was the largest proportion (46.43%) in the NM group, followed by adenocarcinoma (34.10%). The OM group were treated with chemotherapy (55.17%), while the NM group received both chemotherapy (39.93%) and surgical treatment (37.06%). Significant differences were detected in the concentrations of cancer antigen (CA)−125, CA-199, CA-153, alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cytokeratin fraction 21-1 (CYFRA21-1), total prostate-specific antigen, alkaline phosphatase, and hemoglobin (Student's t-test). Binary logistic regression analysis indicated that CA-199, CA-153, AFP, CEA, and CYRFA21-1 were independent risk factors for lung cancer metastasis. AFP (98.3%) and CEA (89.3%) exhibited the highest sensitivity and specificity, respectively, while CYRFA21-1 had the highest area under the ROC curve value (0.875), with sensitivity and specificity values of 77.6 and 87.0%, respectively. Hence, CYFRA21-1 had the best diagnostic value.

Lymphocyte activating gene 3 protein expression in nasopharyngeal carcinoma is correlated with programmed cell death-1 and programmed cell death ligand-1, tumor-infiltrating lymphocytes

Background Immunotherapy has shown promising efficacy in patients with nasopharyngeal carcinoma (NPC). Lymphocyte activating 3 gene (LAG-3) represents a significant immune target, however, its relationship with NPC remains unclear. This study aimed to evaluate LAG-3 expression in NPC and its association with CD3+ tumor-infiltrating lymphocytes (TILs), Granzyme B (GZMB), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) expression. Methods A total of 182 patients with NPC from Sun Yat-sen University Cancer Center, China, were included in this retrospective study. LAG-3 expression in 15 NPC cell lines and LAG-3, CD3+ TILs, GZMB, PD-L1 and PD-1 in clinical samples were estimated using immunohistochemistry. The Chi-square test was used to estimate the association between LAG-3, other biomarkers, and clinical characteristics. Survival analysis was performed using the Kaplan–Meier method and the Cox regression model. Results LAG-3 was negatively expressed in all of the 15 NPC cell lines, whereas, 147 patients with NPC (80.8%) exhibited high LAG-3 expression on TILs from tumor tissues. Male patients and those who were EBV-positive presented higher LAG-3 expression. Correlation analyses showed that LAG-3 expression was related to PD-1 expression on TILs, as well as, PD-L1 expression on tumor cells (TCs) and TILs. Both the univariate and multivariate Cox models indicated that pathological type III (P = 0.036), higher LAG-3 on TILs (P < 0.001), higher PD-L1 on TCs (P = 0.027), and higher PD-1 on TILs (P < 0.001) were associated with poorer disease-free survival (DFS). However, lower PD-L1 expression on TILs was related to superior DFS only in the univariate Cox analyses (P = 0.002). Conclusion Higher LAG-3 and PD-1 on TILs, and higher PD-L1 expression on TCs, and pathological type III were identified as independent risk factors for poorer DFS in NPC patients. Our data demonstrate that LAG-3 is a promising inhibitory receptor that may play an important role in anti-NPC therapy.

Prognosis of Pancreatic Cancer in Hamadan, Iran (2008-2018): A case Series Study

Background: The present study aimed to determine the prognosis of pancreatic cancer from 2008 to 2018 in Hamadan, Iran. A case series study was conducted retrospectively at Beheshti Hospital in Hamadan, Iran. Methods: A total of 409 cases that had been diagnosed with pancreatic cancer from 2008 to 2018 were assessed. The variables included age, gender, pathological type, location involved, early symptoms, metastasis, prognosis and treatments, was extracted from the files and recorded in checklist. Data were analyzed by using SPSS/20 software. Results: The mean of age was 66.23±13.06 year. The most frequent of pancreatic cancers was Adenocarcinomas (66.7%). The highest frequency of early symptoms was jaundice (53.1%) and weight loss (12.7%). The highest frequency of pancreatic cancer lesions was more in the head of pancreas (68.7%). Most patients had metastasis at the beginning of diagnosis (82.3%). Most metastases were in liver (31.5%) and peritoneum (25.2%). The prognosis of the pancreatic cancer is significantly related to the lesion location and the consumption of alcohol, cigarettes and substance abuse (p <0.05), but it wasn’t correlated with age, sex and pathological type (p> 0.05). The 1-year and 5-year survival rates were (22.3%) and (9.5%), respectively. The lowest and the highest in 5-year survival rate were (7.8%) and (18.8%) in adenocarcinoma and carcinoma type. Conclusion: More preventive considerations were found to be beneficial among this population.