[Evaluation of different staging systems and prognostic analysis of 110 primary gastrointestinal diffuse large B cell lymphoma].

Objective: To compare the prognostic efficiency of Lugano staging, TNM staging and Musshoff staging systems in patients with primary gastrointestinal diffuse large B-cell lymphoma(PGI-DLBCL) and investigate its clinical features and prognosis. Methods: The clinical data of 110 patients with PGI-DLBCL in Tianjin Medical University Cancer Institute and Hospital from May 2008 to August 2017 was retrospectively analyzed. The stage of lymphoma was assessed following Lugano staging, TNM staging and Musshoff staging systems respectively. The prognostic value was compared mainly according to the situation of 5-year overall survival (OS)and the influence of different clinical features on prognosis of patients was also investigated. Results: The median age of the whole study was 55(range 17-92) years old. With a median follow-up time of 36 (range 1-115) months, the median progression-free survival (PFS) was 35 (range 0-86) months, and the median overall survival was 37 (range 2-104) months. The 5-year OS rate of Lugano stagingⅠ, Ⅱ, Ⅲ and Ⅳ were 77.6%, 73.4%, 69.7%, 12.2% (χ(2)=63.395, P<0.001) respectively. The 5-year OS rate of TNM staging Ⅰ, Ⅱ, Ⅲ and Ⅳ were 77.6%, 75.9%, 25.0%, 9.3% (χ(2)=65.802, P<0.001) respectively. The 5-year OS rate of Musshoff stagingⅠ, Ⅱ, Ⅲ and Ⅳ were 84.5%, 68.4%, 25.0%, 9.3% (χ(2)=66.966, P<0.001) respectively. By Cox multiple-factors analysis, Lugano staging system was the only independent prognosis risk factor for PFS (HR=4.987, 95%CI: 1.421-17.498, P=0.009) and OS (HR=5.659, 95%CI: 1.563-20.485, P=0.008) of PGI-DLBCL. Univariated analysis revealed that the factors affecting PFS and OS of patients with PG-DLBCL include B-symptom, Eastern Cooperative Oncology Group performance status (ECOG PS), the number of extranodal lesions, serum lactate dehydrogenase (LDH), International prognostic index (IPI) score, staging and therapeutic regimen(all P values of PFS and OS<0.05). Patients with PG-DLBCL who received chemotherapy alone showed a better survival than others (PFS P=0.004; OS P<0.001); the factors affecting PFS and OS of patients with PI-DLBCL include ß2-microglobulin(ß2-MG), serum albumin(ALB) levels, LDH and staging (all P values of PFS and OS<0.05). Therapeutic regimen didn't affect those patients' survival (PFS P=0.661, OS P=0.720). The additional use of Rituximab failed to improve the survival of patients with PG-DLBCL and PI-DLBCL respectively (all P values of PFS and OS>0.05). Conclusions: Compared with TNM staging and Musshoff staging systems, Lugano staging system provides the best prognostic value in PFS and OS for patients with PGI-DLBCL. Accompany with B-sympto, higher ECOG PS score, more extranodal lesions, increased LDH, higher IPI score and later period are negative factors for PG-DLBCL. Increased ß2-MG and LDH, lower ALB level and later period are negative factors of PI-DLBCL.

TGF-ß1 polymorphisms and familial aggregation of liver cancer in Guangxi, China.

The goal of present study was to investigate the relationship between polymorphisms of TGF-ß1 and familial aggregation of liver cancer in Guangxi Zhuang, Han, and Yao populations. We conducted a population-based case-control family study of liver cancer in Guanxi, China. A total of 214 individuals from 37 case families were surveyed for polymorphisms in TGF-ß1. We genotyped six functional TGF-ß1 polymorphisms: rs1800469, rs2241715, rs2241716, rs11466345, rs8105161, and rs747857. Levels of TGF-ß1, hepatitis B surface antigen, and anti-hepatitis C virus in all serum samples were detected using the enzyme-linked immunoassay method, and presence of hepatitis B virus (HBV) DNA was determined using polymerase chain reaction amplification. A standardized questionnaire was used to collect information from subjects, including alcohol consumption, smoking, eating, and water drinking habits. The results were compared with those from 214 control individuals. The results showed that the TGF-ß1 genotypes rs1800469, rs2241715, rs2241715, and rs8105161 were more frequent in patients than in controls. The risk factors for familial aggregation of liver cancer in Guangxi were determined, from high to low, to be: drinking sugared beverages > alcohol consumption > HBV DNA-positive > rs1800469 TT homozygous genotype > rs2241715 TT homozygous genotype. The results suggested that TGF-ß1 rs1800469 TT and rs2241715 TT homozygote genotypes represent the genetic factors underlying familial clustering of liver cancer in Guangxi, and that drinking water use, alcohol consumption, and testing positive for HBV DNA are the main environmental factors contributing to familial aggregation of liver cancer in Guangxi.

HNF1b is involved in prostate cancer risk via modulating androgenic hormone effects and coordination with other genes.

Prostate cancer is one of the most commonly diagnosed male malignancies. Genome wide association studies have revealed HNF1b to be a major risk gene for prostate cancer susceptibility. We examined the mechanisms of involvement of HNF1b in prostate cancer development. We integrated data from Gene Expression Omnibus prostate cancer genes from the Dragon Database of Genes Implicated in Prostate Cancer, and used meta-analysis data to generate a panel of HNF1b-associated prostate cancer risk genes. An RT-PCR was used to assess expression levels in DU145, PC3, LNCaP, and RWEP-1 cells. Twelve genes (BAG1, DDR1, ERBB4, ESR1, HSPD1, IGFBP2, IGFBP5, NR4A1, PAWR, PIK3CG, RAP2A, and TPD52) were found to be associated with both HNF1b and prostate cancer risk. Six of them (BAG1, ERBB4, ESR1, HSPD1, NR4A1, and PIK3CG) were mapped to the KEGG pathway, and submitted to further gene expression assessment. HNF1b, NR4A1, and HSPD1 were found to be highly expressed in the LNCaP androgenic hormone-dependent cell line. Compared to expression levels in wild-type prostate cancer cells, NR4A1, HSPD1, ERBB4, and ESR1 expression levels were also found to be significantly increased in the HNF1b-transfected cells. We conclude that the mechanism of action of HNF1b in prostate cancer involves modulation of the association between androgenic hormone and prostate cancer cells. Gene-gene interaction and coordination should be taken into account to determine relationships between specific loci and diseases.

Key pathways involved in prostate cancer based on gene set enrichment analysis and meta analysis.

Prostate cancer is one of the most common male malignant neoplasms; however, its causes are not completely understood. A few recent studies have used gene expression profiling of prostate cancer to identify differentially expressed genes and possible relevant pathways. However, few studies have examined the genetic mechanics of prostate cancer at the pathway level to search for such pathways. We used gene set enrichment analysis and a meta-analysis of six independent studies after standardized microarray preprocessing, which increased concordance between these gene datasets. Based on gene set enrichment analysis, there were 12 down- and 25 up-regulated mixing pathways in more than two tissue datasets, while there were two down- and two up-regulated mixing pathways in three cell datasets. Based on the meta-analysis, there were 46 and nine common pathways in the tissue and cell datasets, respectively. Three up- and 10 down-regulated crossing pathways were detected with combined gene set enrichment analysis and meta-analysis. We found that genes with small changes are difficult to detect by classic univariate statistics; they can more easily be identified by pathway analysis. After standardized microarray preprocessing, we applied gene set enrichment analysis and a meta-analysis to increase the concordance in identifying biological mechanisms involved in prostate cancer. The gene pathways that we identified could provide insight concerning the development of prostate cancer.

[The prognostic impact of diabetic mellitus and hyperglycemia during DLBCL treatment on patients with diffuse large B-cell lymphoma].

Objective: This study aims to investigate the clinical features and prognostic factors of patients with diffuse large B-cell lymphoma (DLBCL) and assess the prognostic value of diabetes mellitus (DM) and hyperglycemia during DLBCL treatment in DLBCL. Methods: The clinical data of 481 newly diagnosed DLBCL patients from January 1, 2009 to December 31, 2019 at Tianjin Medical University Cancer Institute and Hospital and Sun Yat-sen University Cancer Center were retrospectively collected, focusing on their blood glucose levels before and during treatment. Cox regression method was used for univariate analysis to assess prognostic factors, and the Kaplan-Meier method was used to draw survival curves to assess the prognostic value of DM and hyperglycemia during DLBCL treatment in patients with DLBCL. Results: Eighty-two (17.0%) patients had DM before DLBCL diagnosis and treatment, and 88 (18.3%) patients had at least one blood glucose increase during DLBCL treatment. Cox univariate analysis showed that age, Ann Arbor stage, international prognostic index, and DM were associated with overall survival (OS) and progression-free survival (PFS) (all P<0.05) . The pairwise comparison between the two groups showed that the OS (P=0.001) and PFS (P<0.001) of patients with pre-existing DM were significantly worse than those of patients without abnormal blood glucose. Moreover, the OS (P=0.003) and PFS (P<0.001) of patients with hyperglycemia during DLBCL treatment were significantly worse than those of patients without abnormal blood glucose. No significant difference exists between patients with DM and patients with hyperglycemia during DLBCL treatment (OS, P=0.557; PFS, P=0.463) . Additionally, patients with adequate glycemic control during chemotherapy had a better prognosis compared with patients with poor glycemic control (OS, P=0.037; PFS, P=0.007) . Conclusion: DM is an important factor affecting the prognosis of patients with DLBCL. Moreover, hyperglycemia during treatment is related to the poor prognosis of patients with DLBCL.

AML1/ETO cooperates with HIF1α to promote leukemogenesis through DNMT3a transactivation.

The mechanisms by which AML1/ETO (A/E) fusion protein induces leukemogenesis in acute myeloid leukemia (AML) without mutagenic events remain elusive. Here we show that interactions between A/E and hypoxia-inducible factor 1α (HIF1α) are sufficient to prime leukemia cells for subsequent aggressive growth. In agreement with this, HIF1α is highly expressed in A/E-positive AML patients and strongly predicts inferior outcomes, regardless of gene mutations. Co-expression of A/E and HIF1α in leukemia cells causes a higher cell proliferation rate in vitro and more serious leukemic status in mice. Mechanistically, A/E and HIF1α form a positive regulatory circuit and cooperate to transactivate DNMT3a gene leading to DNA hypermethylation. Pharmacological or genetic interventions in the A/E-HIF1α loop results in DNA hypomethylation, a re-expression of hypermethylated tumor-suppressor p15(INK4b) and the blockage of leukemia growth. Thus high HIF1α expression serves as a reliable marker, which identifies patients with a poor prognosis in an otherwise prognostically favorable AML group and represents an innovative therapeutic target in high-risk A/E-driven leukemia.