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Objective:To investigate the expression of PIK3CA and PTEN in PI3K/Akt/Mtor signaling pathway and its correlation with clinicopathological parameters in invasive B-cell lymphoma.Methods:A total of 235 invasive B-cell lymphoma cases enrolled in First Affliated Hospital of Xinjiang Medical University from January 2008 to December 2012,without any pre-operative treatment,were collected;those included 205 cases of diffuse large B-cell lymphoma(DLBCL),27 cases of Burkitt lymphoma(BL),and the remaining three cases were somewhere between DLBCL and BL,but could not be classified clearly.The expression of PIK3CA and PTEN genes was detected by fluo-rescence in situ hybridization.The relationship between PIK3CA and PTEN genes was analyzed statistically and extended to clinicopathological parameters and prognosis.Results:The positive rate of PIK3CA amplification in invasive B-cell lymphoma was 12.3%(29/235),and the positive rate of clinical stageⅠ-Ⅱ(8.6%,12/139)was much lower than that ofⅢ-Ⅳ(17.7%,17/96),with the difference being statistically significant (P=0.038).The deletion rate of PTEN in invasive B cell lymphoma was 13.6%(32/235),which was not correlated with other clinicopathological features.PIK3CA amplification was negatively correlated with PTEN deletion(P=0.046),and neither was found to be significantly associated with survival.Conclusions:PIK3CA amplification and PTEN deletion play a role in the development of invasive B-cell lymphoma,and the former is associated with late stage of the disease.
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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 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 study the associations between variants of mTORC1 of PI3K/AKT/mTOR pathway and colorectal cancer.@*Methods@#In this hospital-based case-control study, at the First Affiliated Hospital, Xinjiang Medical University from 2000 to 2013, 665 primary colorectal cancer cases and 695 cancer-free controls were genotyped at 10 potentially functional single nucleotide polymorphism (SNPs) loci of mTORC1 (mTOR: rs1034528, rs2295080; Raptor: rs1062935, rs3751934; mLST8: rs3160, rs26865; DEPTOR: rs2271900, rs4871827; AKT1S1: rs2290774, rs2353005) to assess their associations with risk of colorectal cancer by Logistic regression analysis.@*Results@#In single-locus analysis, found a significantly decreased risk of colorectal cancer associated with mLST8 rs26865 by recessive genetic model, especially in populations of ≤68 years of age (OR=0.64; 95%CI=0.43-0.96, P=0.031), female (OR=0.61; 95%CI=0.38-0.99, P=0.046), non-smoking (OR=0.55; 95%CI=0.35-0.87, P=0.010). mTOR rs1034528 CC genotypes were associated with higher risk of colorectal cancer in >68-year-old populations (OR=3.34; 95%CI=1.12-9.91, P=0.030). Raptor rs3751934 CA/AA genotypes were associated with lower colorectal cancer risk in population of body mass index(BMI)>25 kg/m2 (OR=0.68; 95%CI=0.47-0.98, P=0.038); and AKT1S1 rs2290774 CC genotypes were associated with lower colorectal cancer risk in non-smoking population (OR=0.67; 95%CI=0.45-0.99, P=0.048). Furthermore, found that populations carrying more than two low-risk genotypes were associated with lower colorectal cancer risk, compared with that of populations carrying less than two low-risk genotypes (OR=0.74, 95%CI=0.58-0.95, P=0.017), especially in population of ≤68 years of age, male and BMI>25 kg/m2, and non-smoking.@*Conclusions@#SNPs of mTORC1-related genes individually or jointly contribute to colorectal cancer susceptibility in Chinese. Further studies of larger cohorts are needed to validate the findings.
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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.