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This study investigated the expression of the phospholipase C epsilon 1 (PLCE1) and nuclear factor-kappaB (NF-κB)-related proteins in Kazakh patients with esophageal squamous cell carcinoma (ESCC). Tissue microarrays of 90 ethnic Kazakh patients with ESCC and exhibiting clinical characteristics were analyzed for protein expression of PLCE1, IKKβ, IKBα, p50, and p65 by immunohistochemistry. Correlations between histoscores of PLCE1 and NF-κB-related proteins were determined using Spearman's rank correlation tests. Expression of PLCE1 and NF-κB-related proteins significantly increased in tumor tissues compared with normal esophageal tissues (P = 9.48 × 10(-7), 1.24 × 10(-5), 0.004, 0.003, and 2.83 × 10(-5), respectively). Upregulation of PLCE1 was significantly correlated with advanced tumor-node-metastasis stages (P = 0.018) and lymph node metastasis (P = 0.003). Overexpression of IKKβ and IKBα was associated with ESCC stages I/II (P = 3.36 × 10(-4) and 0.022, respectively). Increased expression of p50 was significantly higher in patients with lymph node metastasis than without lymph node metastasis (P = 0.048). Elevated expression of p65 protein was significantly correlated with poor and moderately differentiated ESCC and depth of tumor invasion (P = 0.026 and 0.010, respectively). Significant positive correlations were observed between the expression of PLCE1 and NF-κB-related proteins, especially IKKβ (r = 0.246 and P = 0.025) and p50 (r = 0.244 and P = 0.024). These results suggest, for the first time, that upregulation of PLCE1 is correlated with increased expression of NF-κB-related proteins in Kazakh patients with ESCC, suggesting that interaction between PLCE1 with the NF-κB signal pathway may be responsible for the carcinogenesis of ESCC, such as ESCC-related inflammation.

Background‘Double-hit’ lymphoma (DHL) and ‘double-expression’ lymphoma (DEL) involving gene rearrangement and protein expression of MYC and BCL2/BCL6 have recently become the most commonly used terms to describe the poor prognostic types of diffuse large B-cell lymphoma (DLBCL). However, the clinical and pathological spectra of these rare entities have not been well defined. The aim of this study was to determine the frequency of DHL and DEL in DLBCL and their prognostic impacts in the era of cyclophosphamide, doxorubicin, vincristine and prednisone plus rituximab therapy.MethodsThe data and tissues from 98 patients diagnosed with DLBCL were used in this study. Formalin-fixed and paraffin-embedded tissues were constructed for immunohistochemistry (IHC) and interphase fluorescene in situ hybridisation (FISH) analysis for MYC, BCL6 and BCL2 rearrangements.ResultsThere were 14 cases (14.29%, 14/98) and 34 cases (34.70%, 34/98) of lymphomas with the DHL and DEL of MYC and BCL2/BCL6, respectively. DLBCL patients with MYC/BCL2 rearrangements more frequently had bone marrow involvement (p=0.002), and their tumours were commonly of the germinal centre B cell (GCB) subtype. Patients with MYC+/BCL2 +coexpression were more often assessed using the International Prognostic Index (IPI), (Performance Status) PS score and bone marrow involvement. Patients with MYC+/BCL6 +coexpression were associated with their IPI values, Eastern Cooperative Oncology Group scores and occurrence of B symptoms. Their lymphomas were more often of the non-GCB subtype (p=0.010). Multivariate analysis showed that IPI, bone marrow involvement, rearrangements of BCL2, BCL6 and MYC, expression concurrent with rearrangements and coexpression were all significantly associated with overall survival and progression-free survival, with the exception of MYC+/BCL6 +coexpression.ConclusionsMYC/BCL2 DHL, MYC/BCL6 DHL and MYC/BCL2 DEL are an aggressive B cell lymphoma and patients have a poor prognosis. IPI and bone marrow involvement were independent prognostic factors for DHL and DEL. BCL2, BCL6 and MYC rearrangements translocation, expression concurrent rearrangements and coexpression were were independent prognostic factors for survival.Potential implicationsThe present study analysed the genomic alterations and protein expression levels of MYC, BCL2 and BCL6 using FISH and IHC in Chinese patients with DLBCL.We assessed the frequency, clinicopathological features and the prognostic impacts of DHL and DEL in a cohort of de novo DLBCL patients and evaluated the role of each genetic translocation separately and in combination in order to provide reliable conclusions and practical recommendations for diagnostic workups and prognostic predictions.

The KRAS gene mutation is involved in several types of tumors. However, the potential role of the KRAS mutation in human primary and paired metastatic colorectal cancer (CRC) among different nationalities is poorly understood. In the present study, we assessed the relationship between KRAS mutation status and overall survival (OS) and disease-free survival (DFS) in 230 patients with primary and paired metastatic CRC. The KRAS mutation rate in primary CRC tissue was 43.0% (99/230), which was higher than in paired metastatic CRC, which was 31.9% (23/72; P<0.001). Clinicopathologically, the KRAS gene mutation rate was higher in tumors that had infiltrated more deeply (T3, T4) and in lymph node (LN) metastases (N1/N2) (P=0.029 and P=0.010, respectively). The KRAS gene status did not differ between the Han and Uyghur nationalities in both primary and metastatic CRC. In 72 paired cases, the KRAS mutation rate in primary CRC was significantly higher than in metastatic CRC (P<0.001) and in metastatic CRC that had infiltrated more deeply (T3, T4) (P=0.034). In the metastatic cases, the KRAS gene mutation rate was higher in patients aged over 65 years (P=0.035). Specifically, KRAS mutation was correlated with a poorer OS and DFS (P=0.004 and P=0.029, respectively). In our study, 35 patients with wild-type KRAS who received cetuximab targeted therapy had a better DFS than patients with mutant KRAS (P=0.029). The results of the current study demonstrate that the KRAS status is significantly associated with infiltrating LN metastases and the TNM stage in primary CRC. In addition, the results show that the KRAS mutation is significantly more common in primary tumors than in paired metastatic CRC, and the KRAS mutation is correlated with a shorter OS and DFS, as patients with wild-type KRAS who received cetuximab experienced a longer DFS.

This retrospective study is to explore the clinicopathologic, immunophenotypic, and molecular genetic features of Waldeyer ring B-cell lymphoma (WR-BCL). Tissue arrays from 65 WR-BCL cases were subjected to pathologic and immunophenotypic detections. Expression of Epstein–Barr virus-encoded small RNA (EBER) was detected by in situ hybridization. Interferon regulatory factor 4 (IRF4), BCL-2, BCL-6, and C-myelocytomatosis viral oncogeneav (MYC) gene abnormalities were investigated using interphase fluorescence in situ hybridization. Among the 65 patients, there were 12 nasopharynx cases, 49 tonsil cases, and 4 tongue root cases. Moreover, there were 49 cases of diffuse large BCL (DLBCL) and 16 cases of follicular lymphoma (FL). More than 60% of the patients had Ann Arbor stage III/IV disease, with infiltrated neighboring organs, invaded spleens, and increased lactate dehydrogenase (LDH) levels. Tumor cells were positive for multiple myeloma antigen 1 (MUM1), BCL-2, BCL-6, and C-MYC. EBER expression was detected in lymphoma cells of 2 cases. Alteration frequencies of IRF4, BCL-2, BCL-6, and C-MYC were 24.6%, 32.3%, 27.7%, and 30.7%, respectively. Approximately 67.69% cases had stages 0 to II disease, while 32.31% cases had stage III disease. Five-year overall survival rate was 65.12%. Eastern Cooperative Oncology Group performance status (ECOG) score ≥2 was the only adverse factor for overall survival. IRF4/MUM1, C-MYC, and CD10 expressions were related to poor disease prognosis. WR-BCLs were largely dependent on ECOG, LDH, and bone marrow involvement. WR-DLBCL was associated with poor survival outcomes compared with WR-FL. The WR-DLBCLs have distinct clinicopathologic features, with correlations between the IRF4/MUM1, C-MYC and CD10 expressions, ECOG, LDH, bone marrow involvement, and the disease prognosis.

Background &amp; aimsThe immune checkpoint recently provides a new strategy for the immunotherapy of malignant tumors. However, the role in the immune microenvironment of DLBCL is not completely clear.MethodsWe detected the expression of PD-1, LAG-3, TIM-3, and TIGIT on TILs and on tumor cells among 174 DLBCL patients by IHC.ResultsIn TILs, the positive rates of PD-1, LAG-3, TIM-3 and TIGIT were 79.3%, 78.8%, 62.7% and 69.5%, respectively.TIM-3 and TIGIT were expressed in 44.8% and 45.4% of tumor cells. The expression of TIM-3 in TILs was significantly correlated with the Ann-Arbor stage (P=0.039). There was a positive correlation Between PD-1 and LAG-3 or TIM-3 and TIGIT.In addition, LAG-3 expression in TILs was associated with inferior prognosis.Multivariate analysis showed that PS score and R-CHOP therapy were independent risk factors for OS and PFS in patients with DLBCL (P=0.000).ConclusionsThe expression level of TIM-3 is closely related to the Ann-Arbor stage, which may be expected to be a new index to evaluate the invasiveness of DLBCL. PD-1 was correlated with the expression of LAG-3, and the high expression of LAG-3 and LAG-3/PD-1 predicted the poor prognosis of DLBCL. Therefore, LAG-3 may become a new target of immunotherapy, or be used in combination with PD-1 inhibitors to improve the drug resistance of current patients with DLBCL.

Retraction type (multiple responses allowed):  Unreliable findings   Lab error  Inconsistent data  Analytical error  Biased interpretation   Other:  Irreproducible results  Failure to disclose a major competing interest likely to influence interpretations or recommendations  Unethical research   Fraud   Data fabrication  Fake publication  Other:  Plagiarism  Self plagiarism  Overlap  Redundant publication *  Copyright infringement  Other legal concern:  Editorial reasons   Handling error  Unreliable review(s)  Decision error  Other: ✘ Other: Results of publication (only one response allowed): ✘ are still valid.  were found to be overall invalid.

Mitochondrial ribosome protein L51 (MRPL51) is a 39S subunit protein of the mitochondrial ribosome. Its dysregulation may be involved in non-small cell lung cancer. The present study aimed to explore MRPL51 expression in lung adenocarcinoma (LUAD) and normal lung tissues, as well as its regulatory effects on malignant LUAD behaviors. In addition, the role of forkhead box protein M1 (FOXM1) in MRPL51 transcription was studied. Bioinformatics analysis and subsequent in vitro experiments, including western blotting, immunofluorescent staining, Transwell invasion assay, dual-luciferase assay and chromatin immunoprecipitation quantitative PCR were conducted. The results demonstrated that MRPL51 expression was upregulated at both the mRNA and protein levels in LUAD tissues compared with normal lung tissues. Gene Set Enrichment Analysis demonstrated that LUAD tissues with higher MRPL51 expression also had higher expression levels of genes enriched in multiple gene sets, including ‘DNA_REPAIR’, ‘UNFOLDED_PROTEIN_RESPONSE’, ‘MYC_TARGETS_V1’, ‘OXIDATIVE_ PHOSPHORYLATION’, ‘MTORC1_SIGNALING’, ‘REACTIVE_OXYGEN_SPECIES_PATHWAY’, ‘MYC_ TARGETS_V2’, ‘E2F_TARGETS’ and ‘G2M_ CHECKPOINT’. MRPL51 expression was positively correlated with ‘cell cycle’, ‘DNA damage’, ‘DNA repair’, epithelial-mesenchymal transition (‘EMT’), ‘invasion’ and ‘proliferation’ of LUAD cells at the single-cell level. Compared to the negative control, MRPL51 knockdown decreased N-cadherin and vimentin expression but increased E-cadherin expression in A549 and Calu-3 cells. MRPL51 knockdown suppressed cell proliferation, induced G1 phase arrest and decreased cell invasion. Patients with LUAD and higher MRPL51 expression had a significantly shorter overall survival (OS). FOXM1 could bind to the MRPL51 gene promoter and activate its transcription. In conclusion, MRPL51 was transcriptionally activated by FOXM1 in LUAD and contributed to the malignant behaviors of tumor cells, including EMT, cell cycle progression and invasion. High MRPL51 expression may be a prognostic biomarker indicating poor OS.