Glucose metabolism and systemic inflammation have been associated with cancer aggressiveness and patient prognosis in various malignancies. This study aimed to evaluate the prognostic significance of pretreatment GLR(glucose to lymphocyte ratio) and systemic immune inflammation in patients with pancreatic cancer. We studied 360 patients with pathologically diagnosed pancreatic adenocarcinoma that was clinically unresectable. Baseline clinicopathological characteristics and laboratory investigations including fasting blood glucose, platelet count, lymphocyte count, neutrophil count, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA199), and follow-up data were collected for further analysis. The patients were randomly divided into a training cohort (n = 238) and a validation cohort (n = 122). Univariate and multivariate Cox proportional hazard regression analyses were performed to identify the prognostic value of GLR, systemic immune-inflammation markers, and tumor biomarkers. A nomogram model was developed based on the identified prognostic factors, and we used the C-index to evaluate the accuracy of the Cox regression model prediction. Multivariate analysis revealed that GLR [hazard ratio (HR): 2.597; 95% confidence interval (CI): 1.728–3.904)] and CA199 (HR: 2.484; 95% CI: 1.295–4.765) are independent predictors of poor overall survival in the training cohort and were incorporated into the nomogram for OS as independent factors. Moreover, the C-index analyses demonstrated that the C-indexes in the training cohort and the validation cohort were 0.674 and 0.671, respectively. The nomogram model predicts overall survival relatively accurately. We found that the baseline GLR is an independent prognostic factor for patients with pancreatic cancer, and the proposed nomogram can be used as an effective tool for predicting the outcomes of prognosis of patients with pancreatic cancer.
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type of non-Hodgkin lymphoma (NHL). It is strongly correlated to the host immunity and infection status.
Lung cancer is one of the leading causes of death among cancer patients worldwide. Carbon‐ion radiotherapy is a radical nonsurgical treatment with high local control rates and no serious adverse events. N6‐methyladenosine (m6A) modification is one of the most common chemical modifications in eukaryotic messenger RNA (mRNA) and has important effects on the stability, splicing, and translation of mRNAs. Recently, the regulatory role of m6A in tumorigenesis has been recognized more and more. However, the dysregulation of m6A and its role in carbon‐ion radiotherapy of non‐small‐cell lung cancer (NSCLC) remains unclear. In this study, we found that the level of methyltransferase‐like 3 (METTL3) and its mediated m6A modification were elevated in NSCLC cells with carbon‐ion radiotherapy. Knockdown of METTL3 in NSCLC cells impaired proliferation, migration, and invasion in vitro and in vivo. Moreover, we found that METTL3‐mediated m6A modification of mRNA inhibited the decay of H2A histone family member X (H2AX) mRNA and enhanced its expression, which led to enhanced DNA damage repair and cell survival.
1 August 2016 in Biochemical and Biophysical Research Communications
Two hundred twenty-four breast cancer patients with paired tissue and plasma samples were enrolled from 3 clinical centers to evaluate sensitivity and specificity of a digital PCR HER2 amplification assay. All patients were histologically confirmed diagnosis of locally advanced and recurrent or metastatic breast cancer with stage III/IV and had tissue HER2 status determinations using IHC/FISH. For the whole 224 advanced breast cancer patients, the sensitivity between dPCR in plasma and IHC/FISH in tissue samples is 43.75% (42/96), the specificity is 84.38% (108/128) and the overall concordance is 66.96% (150/224). Interestingly, when we looked at stage III, stage IV and recurrent or metastatic breast cancer separately, compared with IHC/FISH in tissue samples, the sensitivity of dPCR in plasma increases from 37.93% (11/29) for stage III to 41.67% (15/36) for stage IV cancer. Recurrent breast cancer patient had an increased sensitivity of 51.61% (16/31). This is consistent with our expectation sensitivity would increase concordantly as tumor burden goes up. On the other hand, specificity decreased from 92.68% (38/41) for stage III to 86.44% (51/59) for stage IV cancer. Recurrent breast cancer patient had a specificity of only 67.86% (19/28). This is, in part, due to inter- and intra-tumor heterogeneity. Many patients determined to be negative for HER2 amplification in tissue biopsy could have HER2 positive tumors at other sites, which was detected by the liquid biopsy. This study suggested the necessity of liquid biopsy for HER2 amplification detection and demonstrated digital PCR can be used as a companion diagnostic tool to determine HER2 amplification status. It also suggested that a liquid biopsy should follow a negative result from tissue biopsy to avoid false negative results especially for late-stage breast cancer patients and ones who experienced relapse or became resistant to current therapy. Future studies should focus on therapeutic effects on patients determined to be HER2 positive through liquid biopsy and collecting additional tissue biopsies to identify HER2 positive tumor when the original tissue biopsy and liquid biopsy don't agree.