Search

Integrin subunit alpha L (ITGAL) was found aberrantly expressed in multiple cancer types, suggesting its essential role in tumorigenesis. Hence, we aimed to explore its definite role in acute myeloid leukemia and emphasize its associations with immunity. Here, we found ITGAL was highly expressed in AML patients and elevated expression was associated with poor prognosis. ITGAL was associated with age and cytogenetic risk classifications, but not relevant to AML driver gene mutations. Univariate and multivariate Cox regression analyses determined ITGAL as an independent prognostic factor. The nomogram integrating ITGAL and clinicopathologic variables was constructed to predict 1-, 3- and 5-year overall survival (OS). Functional analyses revealed that ITGAL was mainly responsible for the production and metabolic process of cytokine. As for immunity, ITGAL was positively associated with MDSCs including iDCs, and macrophages in the TCGA-LAML cohort. We also found that ITGAL was positively associated with most immune checkpoint genes and cytokines. In addition, we found that ITGAL knockdown caused substantial inhibition of cell growth and significant induction of early apoptosis in AML cells. The xenograft study indicated that ITGAL knockdown prolonged the survival of recipient mice. Overall, ITGAL is an independent prognostic factor and is closely related to the number of MDSCs and cytokine production. [ABSTRACT FROM AUTHOR]

Background: Due to the high morbidity and poor clinical outcomes, early predictive and prognostic biomarker identification is desiderated in colorectal cancer (CRC). As a homologue of the Deleted in Colorectal Cancer (DCC) gene, the role of Neogenin-1 (NEO1) in CRC remained unveiled. This study was designed to probe into the effects and potential function of NEO1 in CRC. Methods: Online databases, Gene Set Enrichment Analysis (GSEA), quantitative real-time PCR and western blotting were used to evaluate NEO1 expression in colorectal cancer tissues. Survival analysis was performed to predict the prognosis of CRC patients based on NEO1 expression level. Then, cell proliferation was detected by colony formation and Cell Counting Kit 8 (CCK-8) assays. CRC cell migration and invasion were examined by transwell assays. Finally, we utilized the Gene Set Variation Analysis (GSVA) and GSEA to dig the potential mechanisms of NEO1 in CRC. Results: Oncomine database and The Cancer Genome Atlas (TCGA) database showed that NEO1 was down-regulated in CRC. Further results validated that NEO1 mRNA and protein expression were both significantly lower in CRC tumor tissues than in the adjacent tissues in our clinical samples. NEO1 expression was decreased with the progression of CRC. Survival and other clinical characteristic analyses exhibited that low NEO1 expression was related with poor prognosis. A gain-of-function study showed that overexpression of NEO1 restrained proliferation, migration and invasion of CRC cells while a loss-of-function showed the opposite effects. Finally, functional pathway enrichment analysis revealed that NEO1 low expression samples were enriched in inflammation-related signaling pathways, EMT and angiogenesis. Conclusion: A tumor suppressor gene NEO1 was identified and verified to be correlated with the prognosis and progression of CRC, which could serve as a prognostic biomarker for CRC patients. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to investigate the effect associated with the protein expression of VEGF, JAK2 and STAT3 on the clinicopathologic characteristics and prognosis in the development and progression of nasopharyngeal carcinoma (NPC). Methods: Fifty NPC patients in addition to 20 patients with chronic nasopharyngitis (CNP) were recruited for the purposes of the study. Western blotting and immunohistochemistry methods were employed to evaluate the protein expressions of JAK2, STAT3 and VEGF in the NPC and CNP tissues, with their respective correlations with the clinicopathologic characteristics of NPC patients subsequently analyzed. Spearman’s rank correlation coefficient and Kaplan–Meier method were conducted to evaluate the respective correlations of JAK2, STAT3 and VEGF with NPC as well as the survival rates of patients with NPC. Cox regression analyses was performed in determine the prognostic NPC factors. Results: Compared with the CNP tissues, the NPC tissues exhibited elevated levels of JAK2, STAT3 and VEGF which were subsequently determined to share a positive correlation with T stages, lymph node metastasis (LNM), N stages and clinical stages, while a negative correlation with survival rates were observed in the NPC patients. Positive correlations between the expressions of JAK2, STAT3 and VEGF were detected among the NPC tissues. NPC patients survival time with negative expressions of JAK2, STAT3 and VEGF were observed to be longer than that of NPC patients with positive expressions of JAK2, STAT3 and VEGF. T stage, LNM, N stage, clinical stage. The expressions of JAK2, STAT3 and VEGF were discovered to be independent risk factors associated with the prognosis of patients with NPC. Conclusion: The results obtained from the present study support the notion that higher expressions of JAK2, STAT3 and VEGF may be correlated with the clinicopathologic characteristics and prognosis of patients suffering from NPC. [ABSTRACT FROM AUTHOR]

Background: R-CHOP with or without radiotherapy is the standard treatment for limited-stage diffuse large B-cell lymphoma (DLBCL). To prevent overtreatment, we assessed whether four cycles of CHOP plus six applications of rituximab was adequate with negative interim PET/CT and the role of consolidation radiotherapy specifically for patients with Waldeyer's ring DLBCL. One hundred and twenty-nine patients with limited-stage DLBCL were enrolled in this open-label, nonrandomized, single-arm, phase 2 clinical trial (NCT01804127).Methods: All patients were initially treated with 4 cycles of R-CHOP and underwent interim PET/CT. Patients with negative PET/CT (Deauville scores 1-2) received 2 additional cycles of rituximab monotherapy, unless they had any risk factors (primary mediastinal large B-cell lymphoma, extranodal primary or bulky disease). Otherwise, patients received another 2 cycles of R-CHOP. Patients with partial response on interim PET/CT received another 4 cycles of R-CHOP. No radiotherapy was conducted in Waldeyer's ring DLBCL patients with negative PET/CT. The primary endpoint was 3-year progression-free survival (PFS). Overall survival (OS) in this study was compared with those from a historical study (NCT 00854568159).Results: One hundred fifteen interim PET/CT scans (89.1%) were negative after 4 cycles of R-CHOP. An elevated lactate dehydrogenase level was significantly associated with positive interim PET/CT (P < 0.05). A trend of inferior outcome was observed in patients with positive interim PET/CT in terms of 3-year PFS (78.6% vs. 91.9%, P = 0.24) and 3-year OS (85.7% vs. 95.6%, P = 0.16). There were no PFS or OS differences found between patients treated with 4R-CHOP+2R and those treated with 6R-CHOP from a historical control study. Patients with Waldeyer's ring DLBCL and negative interim PET/CT achieved a 3-year PFS of 87.2% and a 3-year OS of 89.7%.Conclusions: Our results suggested that for interim PET/CT-negative patients without risk factors, the extra 2 cycles of CHOP might be omitted, and radiotherapy might also be omitted in patients with Waldeyer's ring DLBCL without compromising the efficacy. These results need to be confirmed in a randomized study.Trial Registration: clinicaltrials.gov ,  NCT01804127 . Date of first registration: 05/03/2013. [ABSTRACT FROM AUTHOR]