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Objective:To explore the levels of programmed death receptor 1 (PD-1) and lymphocyte activating gene 3 (LAG-3) in the immune microenvironment of diffuse large B-cell lymphoma (DLBCL), their relationship with clinicopathological features, and their impact on prognosis.Methods:The tumor tissue sections and formaldehyde fixed paraffin embedded tissues from 174 DLBCL patients diagnosed at the First Affiliated Hospital of Xinjiang Medical University from February 2012 to August 2017 were retrospectively collected. The tissue chips were prepared, and the immunohistochemistry (IHC) method was used to detect the expressions of PD-1 and LAG-3 proteins in tumor infiltrating lymphocytes (TIL) of tissue chips [including whether they were positive (positive for IHC score 1-9 points, negative for 0 point) and expression level (high expression was 4-9 points on IHC score, low expression was 0-3 points)]. The relationship between the expression levels of PD-1 and LAG-3 and the clinicopathological characteristics of patients was analyzed. Spearman correlation coefficient was used to analyze the correlation between the expression levels of PD-1 and LAG-3. Kaplan-Meier method was used to draw overall survival (OS) and progression free survival (PFS) curves of patients with different expression levels of PD-1 and LAG-3, and log-rank test was used for comparison between the groups. Univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors of OS and PFS in patients.Results:Of the 174 DLBCL patients, 95 (54.6%) were male and 79 (45.4%) were female; the median age was 60 years old (5-87 years old). The proportions of patients with PD-1 and LAG-3 positive in TIL of tumor tissues were 79.3% (138/174) and 78.8% (137/174), and the proportions of patients with high expression were 35.6% (62/174) and 37.9% (66/174), respectively. Among patients with bone marrow involvement, the proportion of patients with high expression of PD-1 [62.5% (15/24) vs. 32.5% (39/120), P= 0.006], the proportion of patients with high expression of LAG-3 [54.2% (13/24) vs. 32.5% (39/120), P= 0.050] were higher than those without bone marrow involvement. The expression levels of PD-1 and LAG-3 were not associated with gender, age, clinical stage, international prognostic index score, functional status (PS) score, lactate dehydrogenase level, whether there were B symptoms, whether it was intranodal, tumor length, whether it was germinal center B cell type, number of extranodal involvement sites, and whether it was treated with R-CHOP regimen (all P > 0.05). There was a positive correlation between PD-1 and LAG-3 expression levels in TIL of tumor tissues ( r = 0.202, P = 0.008). Multivariate Cox regression analysis showed that PS score (>2 points vs. ≤2 points: HR = 5.458, 95% CI 2.082-14.307, P = 0.001), R-CHOP regimen treatment (no vs. yes: HR = 2.181, 95% CI 1.086-4.379, P = 0.028) were independent influencing factors of OS, and PS score (>2 points vs. ≤2 points: HR = 3.913, 95% CI 1.579-9.698, P = 0.003), R-CHOP regimen treatment (no vs. yes: HR = 2.609, 95% CI 1.412-4.819, P = 0.024), LAG-3 expression level (low expression vs. high expression: HR = 0.531, 95% CI 0.283-0.995, P = 0.048) were independent influencing factors of PFS. There were no statistical differences in PFS and OS between patients with high and low PD-1 expression levels in TIL (both P > 0.05). PFS and OS in patients with high LAG-3 expression were worse than those in patients with low expression (both P < 0.05). OS in patients with high expressions of PD-1 and LAG-3 was worse than that in patients with low expressions of PD-1 and LAG-3 ( P = 0.044). Conclusions:The expression levels of PD-1 and LAG-3 in TIL of DLBCL patients' tumor tissues are related to bone marrow involvement, which are not related to most other clinicopathological features, and the prognosis of patients with high expressions of PD-1 and LAG-3 is poor.
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Objective@#To compare different specimen types of lung adenocarcinoma in the detection of epidermal growth factor receptor (EGFR) gene and to correlate EGFR mutations with patient clinical features.@*Methods@#One hundred lung adenocarcinoma cases were collected from June to December in 2015, at the First Affiliated Hospital of Xinjiang Medical University.Of the 100 lung adenocarcinoma samples, 43 were male and 57 were female. The age was from 40 to 88 years old, and the average age was 66 years. One hundred lung adenocarcinoma cases were divided equally into two groups. Mutation analysis of EGFR gene by real-time PCR was performed using biopsied tissue and paired blood samples in one group (n=50) and using pleural effusion and paired blood samples in the other group (n=50).@*Results@#The mutation rate of EGFR gene in biopsy samples was 54% (27/50) , higher than that of blood samples (46%, 23/50), but without statistical differences (χ2=0.640, P=0.424). In contrast, mutation rate of EGFR gene in pleural effusion samples (42%, 21/50) was higher than that of blood samples (34%, 17/50), but without statistical differences(χ2=0.679, P=0.409). Two patients had EGFR mutation detected in paired blood samples but not in the corresponding biopsy samples, and four patients had EGFR mutation detected in pleural effusion samples but not in their paired blood samples. The mean progression-free survival of patients with detectable EGFR mutation were 9.5 months (tissue samples), 8.6 months (pleural effusion) and 8.5 months (blood). However, there was no statistical difference.@*Conclusions@#Blood samples may be used to assess EGFR mutations for patients with lung adenocarcinoma. However, further studies are needed to improve the sensitivity and accuracy in the detection of EGFR mutations using blood samples.
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Objective@#To investigate the role of PRDM1 gene inactivaion in the regulation of C-MYC in diffuse large B-cell lymphoma (DLBCL), and to explore the correlation of its immunophenotype and prognosis.@*Methods@#100 cases paraffin-embedded DLBCL tissues were collected from January 2009 to December 2015 at the First Affiliated Hospital of Xinjiang Medical University along with 20 cases of reactive proliferative lymph nodes as control. Immunohistochemical methods were used to detect the expression of CD20, CD10, MUM1, Ki-67, bcl-6, PRDM1/Blimp1, C-MYC and PAX5 protein. The tumors were classified into two subtypes according to Hans classification.The expression of PRDM1 and C-MYC gene in tumor group and control group was detected by reverse transcription PCR (RT-PCR) and the relationship between PRDM1 and C-MYC gene was analyzed.OCI-LY1 (GCB subtype) and OCI-LY3 (non-GCB subtype) cell lines were transfected with small interfering RNA by cationic liposome reagent transfection, and the expression of C-MYC in the transfected cell lines was detected by RT-PCR and Western blot. The Kaplan-Meier method was used to analyze the prognostic significance of PRDM1/Blimp1 and C-MYC at protein and mRNA levels.@*Results@#There were 27 cases of GCB subtype and 73 cases of non-GCB subtype according to Hans classification. The positive expression of Blimp1 in DLBCL group and proliferative lymph nodes in control group was seen in 26(26.0%) and 20 cases(100%), respectively. There were 58 cases with high expression of PRDM1 at mRNA level, including 22 cases of GCB subtype and 36 cases non-GCB subtype, and the difference was statistically significant (P=0.004). There were differences in PRDM1 gene expression between the two immunological subtypes, serum lactate dehydrogenase (serum LDH) level, presence of B symptoms, tumor primary sites and other clinical pathological parameters, while C-MYC expression was different in gender, IPI score, and serum LDH levels. Upon PRDM1/Blimp1 gene silencing in the two cell lines, C-MYC protein and gene expression were up-regulated in the transfection group, compared with the blank control group and negative control group by reverse transcription PCR and Western blot analyses. Moreover, PRDM1 expression was significantly associated with C-MYC(χ2=7.648, P=0.006) at mRNA level.@*Conclusion@#The up-regulation of C-MYC gene expression induced by PRDM1 inactivation in DLBCL may play an important role for the development of DLBCL.PRDM1 protein and mRNA are associated with immunophenotyping and PRDM1 mRNA is a marker of poor prognosis.
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Objective@#To investigate the point mutation of epidermal growth factor receptor (EGFR) gene and clinicopathologic characteristics in patients with non-small cell lung cancers(NSCLC)of Xinjiang region.@*Methods@#Five-hundred and eighty-two cases of paraffin-embedded tissue in patients with NSCLC were collected between January 2013 and December 2015 in the First Affiliated Hospital of Xinjiang Medical University. The DNA was extracted from these tissues by Qiagen kit, to test thirty-two mutations in EGFR exons 18, 19, 20 and 21 using fluorescent quantitative qRT-PCR technology by TaqMan probe; the clinicopathologic features of patients were analyzed according to the mutation status of EGFR.@*Results@#There were 173 cases with EGFR gene mutation in 582 cases of paraffin-embedded tissue in patients with NSCLC, and the mutation rate was 29.7%(173/582). There were statistical difference in female patients (50.5%, 98/194), no history of smoking(47.3%, 96/203), high differentiation(6/9), adenosquamous carcinoma(6/11), peripheral location (34.9%, 88/252), and surgical specimens(38.2%, 83/217), respectively (P<0.05). Multiple factors Logistic analysis showed that gender, degree of differentiation, and pathologic types had statistical differences to EGFR when α=0.05. There were no statistical differences between other variants.@*Conclusions@#There are higher rate EGFR gene mutation in women patients, non-smokers, and well-differentiated, adenocarcinoma. Gender, degree of differentiation and pathological patterns are independent influencing factors on EGFR mutation status.
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<p><b>OBJECTIVE</b>To study the expression level and clinical significance of miR-181c-3p and miR-5692b in esophageal cancer.</p><p><b>METHODS</b>The microRNA (miRNA) profiles of esophageal squamous cell carcinoma were analyzed by miRNA microarray in 55 cases of esophageal cancer. The expression levels of miR-181c-3p and miR-5692b from 55 pairs of tumor tissues and adjacent non-neoplastic tissues were determined by qRT-PCR analysis.</p><p><b>RESULTS</b>Both miR-181c-3p and miR-5692b were significantly up-regulated in tumor tissues compared with adjacent non-neoplastic tissues. Their expression was also significantly associated with tumor size, depth of invasion and clinical tumor stage (P<0.05). High expression of miR-181c-3p and miR-5692b were significantly associated with poor prognosis (P<0.05). Multivariate Cox regression analysis confirmed that high expression of miR-181c-3p and miR-5692b was poor prognostic indicators in esophageal cancer.</p><p><b>CONCLUSIONS</b>There are significant correlation between miR-181c-3p/miR-5692b expression, clinicopathologic parameters and prognosis. They represent potential prognostic biomarkers in esophageal squamous cell carcinoma.</p>