Analysis of Prognostic Risk Factors and Establishment of Prognostic Scoring System for Secondary Adult Hemophagocytic Syndrome.

INTRODUCTION: The objective of this paper is to identify the prognostic risk factors of secondary adult hemophagocytic syndrome (HLH) in hospitalized patients and establish a simple and convenient prognostic scoring system. METHOD: We reviewed 162 adult patients secondary with HLH treated in Zhejiang Cancer Hospital and the First Affiliated Hospital of Medical College of Zhejiang University from January 2014 to December 2018 were enrolled to form the test group; from January 2019 to February 2021, 162 adult patients in the hospitals constituted the validation group. The HLH prognosis scoring system was constructed according to the risk factors, and the patients were divided into three risk groups: low risk, medium risk, and high risk. The scoring system was verified by Kaplan-Meier method and log rank test survival analysis. The discrimination ability was evaluated according to the receiver operating characteristic (ROC) curve. RESULTS: Univariate and multivariate analysis showed that the independent risk factors for the prognosis of HLH were male sex, activated partial prothrombin time (APTT) greater than 36 s, lactate dehydrogenase (LDH) greater than 1000 U/L, and C-reactive protein (CRP) greater than 100 mg/L. The area under the ROC curve was 0.754 (95% Cl: 0.678-0.829). The patients were divided into a low-risk group (0-1), a medium-risk group (2-4), and a high-risk group (5-6). The 5-year overall survival (OS) rate were 87.5%, 41.8% and 12.8%, respectively (p < 0.001). The area under ROC curve was 0.736 (95% Cl: 0.660-0.813) in the validation group, and the 2-year OS of patients in low-risk, medium-risk and high-risk groups were 88.0%, 45.1% and 16.7%, respectively (p < 0.001). CONCLUSION: The new prognostic scoring system can accurately predict the prognosis of secondary adult HLH and can further provide basis for the accurate treatment of secondary adult HLH.

CDH1 germline mutations in a Chinese cohort with hereditary diffuse gastric cancer.

PURPOSE: Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer (HDGC) and have been identified in multiple ethnicities. However, CDH1 germline mutations have seldom been documented in Chinese patients with HDGC, and their frequency remains unclear. Here, we aimed to examine the frequency of CDH1 germline mutations in Chinese patients with HDGC. In total, 285 patients who met the International Gastric Cancer Linkage Consortium 2015 testing criteria of HDGC for CDH1 germline mutations were recruited. METHODS: All 16 CDH1 exons, including neighboring intronic sequences, were amplified using polymerase chain reaction and screened using Sanger sequencing. Variants were analyzed using Mutation Surveyor V4.0, SIFT, and PolyPhen-2 software. RESULTS: Three nonsense and nine missense CDH1 germline mutations were identified in 21 of 285 index cases (7.4%). Two CDH1 germline mutations, N405Y (Asn405Tyr) and W409X (Trp409Ter), were identified as new variants. In addition, up to 28.6% of CDH1 mutations in the 21 indicated patients were identified as c.1775G>C (E551Q). The frequency of CDH1 mutations was 6.5% (7/108) in HDGC and 7.9% (14/177) in early onset diffuse gastric cancer (EODGC). The mutation detection rates of CDH1 in males and females were 6.7% (4/60) and 8.5% (10/117) in EODGC and 4.6% (3/65) and 9.3% (4/43) in HDGC, respectively. CONCLUSION: These data reveal, for the first time, the type and frequency of CDH1 germline mutations in Chinese HDGC and demonstrate that germline CDH1 mutations are a noteworthy contributor to the high frequency of HDGC in Chinese.

Correction of spurious low platelet counts by optical fluorescence platelet counting of BC-6800 hematology analyzer in EDTA-dependent pseudo thrombocytopenia patients.

BACKGROUND: To evaluate the dissociation effect of optical fluorescence platelet counting of BC-6800 hematology analyzer on ethylene diamine tetraacetic acid-dependent pseudo thrombocytopenia (EDTA-PTCP) samples. METHODS: Twenty-three finally identified EDTA-PTCP samples were recruited in this study using criteria as follow: (I) impedance platelet counts lower than 100×109/L with instrument "platelet aggregation" flag; (II) existence of platelet clumps in the blood smear; (III) obviously higher platelet counts without "platelet aggregation" flag and no platelet clumps in blood smear after repeating phlebotomy using citrate anticoagulated tubes. The BC-6800 hematology analyzer and the XE-2100 hematology analyzer were used to test 23 EDTA-PTCP samples and 30 controls on both the impedance channel and the reticulocyte channel. The dissociation rate was defined as optical fluorescence platelet counts in the EDTA tubes/impedance platelet counts in citrate tubes ×100%. RESULTS: BC-6800 analyzer's optical fluorescence platelet counts of EDTA-PTCP samples were significantly higher than impedance platelet counts (t=4.33, P=0.00) and comparable with the platelet counts of re-collected samples in tubes containing citrate anticoagulant. On BC-6800 hematology analyzer, 22 of 23 EDTA-PTCP samples showed a dissociation rate greater than 80%, and the average dissociation rate was 93%. On the XE-2100 hematology analyzer, 1 of the 17 EDTA-PTCP samples showed a dissociation rate greater than 80%, and the average dissociation rate was 56%. CONCLUSIONS: Optical fluorescence platelet counting of BC-6800 Hematology Analyzer is effective for the correction of spurious low platelet counts in EDTA-PTCP patients, and its dissociation effect on EDTA-PTCP samples was independent of fluorescent dye staining.

The long noncoding RNA CASC9 regulates migration and invasion in esophageal cancer.

The objective of the study was to investigate the expression and functions of CASC9 in esophageal squamous cell carcinoma (ESCC). Long noncoding RNAs (lncRNAs) upregulated in ESCC tissues were detected by RNA sequencing. Expression of CASC9 was determined from clinical samples and cell lines by qRT-PCR. The effects of CASC9 knockdown on migration and invasion were evaluated by wound healing assay, cell migration and invasion assays in vitro. We found that the lncRNA, CASC9, was markedly upregulated in ESCC tissues. Furthermore, knockdown of CASC9 significantly suppressed cell migration and invasion in vitro. Furthermore, enhanced CASC9 expression level was correlated with differentiation. The results indicated that CASC9 is significantly upregulated in ESCC tissues and may represent a new marker of poor prognosis and a potential therapeutic target for esophageal cancer intervention.

Neuronal acetylcholine receptor subunit alpha-9 (CHRNA9) polymorphisms are associated with NSCLC risk in a Chinese population.

Neuronal acetylcholine receptor subunit alpha-9 (CHRNA9) encodes a plasma membrane protein of divalent cation channels and is expressed in keratinocytes. This study aimed to investigate CHRNA9 single-nucleotide polymorphisms (SNPs) for association with non-small cell lung cancer (NSCLC), especially squamous cell carcinoma (SCC) risk, in a Chinese population. This case-control study included 500 NSCLC patients and 500 age-matched healthy controls. CHRNA9 rs56159866, rs6819385, rs55998310, and rs182073550 SNPs were genotyped and associated for NSCLC risk by computing the odds ratios (ORs) and 95 % confidence intervals (CIs) from multivariate unconditional logistic regression analyses with adjustment for age. The frequencies of the CHRNA9 rs6819385 G allele were 16.1, 15.2, and 20.8% in male NSCLC patients, male SCC patients, and male controls, respectively. The CHRNA9 rs6819385 A allele was associated with an increased risk of developing NSCLC (P = 0.04, OR = 1.37; 95% CI 1.02-1.83) and SCC (P = 0.04, OR = 1.47; 95% CI 1.01-2.13). The CHRNA9 rs6819385 A/A homozygote was associated with an increased risk of NSCLC and SCC in all patients (OR = 1.38; 95% CI 1.06-1.79; P = 0.02, and OR = 1.61; 95% CI 1.09-2.38; P = 0.02, respectively) and in male patients (OR = 1.57; 95% CI 1.11-2.21; P = 0.01, and OR = 1.70; 95% CI 1.11-2.61; P = 0.01, respectively), indicating that the CHRNA9 rs6819385 A/A homozygote had a 1.61-fold and 1.70-fold increased risk of developing lung SCC in all patients (95% CI 1.09-2.38, P = 0.02) and in males (95% CI 1.11-2.61, P = 0.01), respectively. The CHRNA9 rs6819385 SNP was significantly associated with an increased risk of NSCLC, especially for SCC in male patients in this Chinese population.

Polymorphisms of CHRNA5-CHRNA3-CHRNB4 Gene Cluster and NSCLC Risk in Chinese Population.

AIM: To explore the potential association between single-nucleotide polymorphisms (SNPs) and haplotypes of the CHRNA5-CHRNA3-CHRNB4 gene cluster and the non-small cell lung cancer (NSCLC) susceptibility in never-smoking Chinese. METHODS: A case-control study was conducted with 200 NSCLC patients and 200 healthy controls, matched on age and sex. Five SNPs distributed in CHRNA5-CHRNA3-CHRNB4 gene cluster were selected for genotyping. The association between genotype and lung cancer risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses with adjustment for gender and age. RESULTS: For CHRNA3 rs578776 status, data were available in 199 NSCLC patients and 199 controls. The G/G homozygote in CHRNB4 rs7178270 had a reduced risk of developing NSCLC (OR = 0.553; 95% CI = 0.309-0.989; P = .0437), especially squamous cell carcinoma (SQC) (OR = 0.344; 95% CI = 0.161-0.732; P = .0043), compared with those who carry at least one C allele (C/C and C/G). The polymorphisms of rs578776, rs938682, rs17486278, and rs11637635 were not significantly different between controls and cases or between controls and histologic subgroups, adenocarcinoma and SQC, respectively. CONCLUSIONS: In our study, we found that the SNP of CHRNB4 rs7178270 is significantly associated with reduced risk of NSCLC, especially with reduced risk of SQC in never-smoking Chinese population.