Application of cerebrospinal fluid free light chain in diagnosis of primary central nervous system lymphoma and monitoring of associated chemotherapy efficacy.

BACKGROUND: Cerebrospinal fluid (CSF) free light chain (FLC) detection has been proposed as a tool for diagnosing primary central nervous system lymphoma (PCNSL), but there is no consensus on the appropriate reference range and its value for monitoring chemotherapy efficacy has not been investigated in Chinese PCNSL patients. We assessed the application potential of CSF FLC ratios for diagnosing PCNSL and monitoring associated treatment efficacy. METHODS: Kappa (κ) and lambda (λ) FLC were measured by nephelometry in CSF samples of patients with PCNSL (n = 45), other neurological diseases (n = 30), and normal controls (n = 60). Results of κ/λ FLC ratios (FLCr) were correlated with patients' diagnoses and receiver operating characteristic analysis was used to determine accuracy. In PCNSL patients, FLCr analysis was compared between PCNSL before and after treatment. RESULTS: κ FLC and FLCr concentrations in PCNSL were significantly higher than in patients without PCNSL (P < 0.05). The optimal cut-off for FLCr was 0.35, with diagnostic sensitivity and specificity of 78% and 72%, respectively. FLCr concentrations decreased after chemotherapy. CONCLUSION: CSF FLC is a novel biomarker for diagnosis and chemotherapy efficacy monitoring in PCNSL.

Mechanisms underlying the promotion of osteosarcoma cell proliferation and invasion by lncRNA PBB12.

PBB12, a long noncoding RNA (lncRNA), has not been reported to be involved in the progression of osteosarcoma to date. According to our research data, it was found that osteosarcoma patients with a high PBB12 level frequently showed increased metastasis. Mechanistic research demonstrated that PBB12 can competitively bind to hsa­miR­204­5p by acting as a microRNA sponge. Furthermore, PBB12 intervenes in the Kruppel­like factor 4 (KLF4)/hsa­miR­204­5p/activating transcription factor 2 (ATF2) pathway and affects the proliferation and invasion of osteosarcoma cells. High PBB12 expression was founld to lead to the loss of function of the cancer suppressors KLF4 and hsa­miR­204­5p; these effects are the intrinsic reason why osteosarcoma patients with high levels of PBB12 often develop tumor metastases. In vitro functional experimental data showed that in the osteosarcoma cell lines MG63 and SAOS­2, PBB12 silencing and overexpression significantly increases or reversed the inhibitory effect of KLF4 on the proliferation and invasion of tumor cells, respectively. The involvement of the interaction between PBB12 and the KLF4/hsa­miR­204­5p/ATF2 pathway in osteosarcoma progression was reported for the first time, and these data provide important theoretical support for gene therapy targeting KLF4 and hsa­miR­204­5p. The great significance of this study is that a high or low genetic background level of PBB12 in osteosarcoma patients may serve as an important marker for screening patients for a high risk of tumor metastasis. Furthermore, for osteosarcoma patients with high PBB12 expression, the primary task for all accurate personalized clinical treatment programs may be the determination of how to effectively knock down PBB12 in tumor bodies.

Inhibition of proliferation and invasion of hepatocellular carcinoma cells by lncRNA-ASLNC02525 silencing and the mechanism.

One of the most differentially expressed long non-coding RNAs (lncRNAs) that we identified by high throughput screening from liver cancer and para-carcinoma tissues, ASLNC02525, was highly expressed in the tissues and cell lines of liver cancer but not in adjacent tissues or normal hepatic cells. Knockdown of ASLNC02525 in hepatocellular carcinoma cells inhibited the proliferation and invasion. In the process, expression level of transcription factor twist1 (twist­related protein 1) was reduced, but no change at transcription level was observed. According to bioinformatics analysis, ASLNC02525 may play a crucial role in inactivation of regulation of twist1 by hsa-miRNA-489-3p. The mechanism study revealed that ASLNC02525, as an RNA sponge, broke the negative regulation of twist1 by hsa-miRNA-489-3p, and once ASLNC02525 was silenced, the highly expressed hsa-miRNA­489-3p regained its regulation on twist1 and inhibited the proliferation and invasion. The importance of this study lies in shedding light on the potential for lncRNAs to become targets for gene therapy, by demonstrating that lncRNAs can suppress tumor inhibiting activity of miRNAs via breaking regulation of some miRNA target genes.

Prognostic significance of stem cell marker CD133 determined by promoter methylation but not by immunohistochemical expression in malignant gliomas.

CD133 has played a pivotal role in the identification and isolation of brain tumor stem cells. The correlation between CD133 expression in tumor tissues with patients survival is still controversial. CD133 expression is determinated by methylation status of the promoter region 1-3. Aberrant methylation of CD133 was observed in glioblastoma. To date, a direct link between CD133 methylation and patient outcome has not been established.To address this question, we studied CD133 expression and promoter methylation in a series of 170 gliomas of various grade and histology, and investigated the correlation of CD133 expression and promoter methylation with patient outcome.We detected five CD133 promoter methylation patterns in 170 glioma samples: methylation only (M+, U-), unmethylation only (M-, U+), both methylation and unmethylation equally (M+, U+), high methylation and low unmethylation (M+, Ul), and low methylation and high unmethylation (Ml, U+). By multivariate survival analysis, we found CD133 promoter methylation status was significant (P < 0.01) prognostic factors for adverse progression-free survival and overall survival independent of tumor grade, extent of resection, or patient age. CD133 immunostaining showed considerable variability among tumors. While, there was lack of correlation between CD133 protein expression and patient's survival. Furthermore, no correlation between CD133 protein expression and CD133 promoter methylation status was observed (Kw = -0.165).CD133 promoter methylation status in glioma is closely correlated with patient survival, which suggest CD133 promoter methylaiton pattern is a promising tool for diagnostic purposes.

High prevalence of hepatitis B virus infection in primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal form of non-Hodgkin lymphoma (NHL). The present study aimed to investigate the potential association between infection with the Hepatitis B virus (HBV) and PCNSL. The prevalence of HBV infection in 199 patients with PCNSL was compared in our hospital with that of an age-and sex-matched group of patients with other cancers (except liver cancer), and with a national population-based control group. Enzyme-linked immunosorbent assays were used to test blood samples for HBV markers. It was found that the prevalence of HBV infection in PCNSL was 16.1%, which was higher as compared with patients with other non-hematologic cancers and the national population-based control group. In conclusion, the present study demonstrated that PCNSL patients had a higher prevalence of HBV infection and suggested a potential association between infection with HBV and PCNSL.

Evaluation of the Sysmex UF-1000i for the diagnosis of urinary tract infection.

Diagnosis of urinary tract infection (UTI) is primarily done by microbiologic culture, which is time-consuming and can produce false-positives and false-negatives. Flow cytometry allows for rapid screening of many samples and eliminates culturing. We analyzed the Sysmex UF-1000i (TOA Medical Electronics, Kobe, Japan) for accuracy in identifying RBCs and WBCs, casts, bacteria, and epithelia. We also evaluated its precision, linear estimation of results, carryover contamination rate, and anti-interference. UF-1000i agreement with manual counting was approximately 95% for RBCs and WBCs, epithelia, and casts. Its coefficient of variation for bacteria ranged from 4.7% to 15.2%. UF-1000i screening for UTIs exhibited great sensitivity (97%), specificity (79%), positive predictive value (70%), negative predictive value (99%), and accuracy (85%). The negative predictive value remained high even with complex UTI samples. The Sysmex UF-1000i shows great promise in excluding more than 50% of true-negative samples, improving detection efficiency, and reducing laboratory costs.