Diffuse large B cell lymphoma (DLBCL) is a common and fatal hematological malignancy. Long noncoding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers. Novel lncRNA biomarker in DLBCL needs to be investigated badly, as well as its function and molecular mechanism. To further explore, microarray analysis was performed to identify the differentially expressed lncRNAs in DLBCL tissues. To investigate the biological functions of SMAD5-AS1, we performed gain- and loss-of-function experiments in vitro and in vivo. Furthermore, bioinformatics analysis, dual-luciferase reporter assays, Argonaute 2-RNA immunoprecipitation (AGO2-RIP), RNA pull-down assay, quantitative PCR arrays, western blot assay, TOPFlash/FOPFlash reporter assay, and rescue experiments were conducted to explore the underlying mechanisms of competitive endogenous RNAs (ceRNAs). We found that SMAD5-AS1 was down-regulated in DLBCL tissues and cell lines. Functionally, SMAD5-AS1 downregulation promoted cell proliferation in vitro and in vivo, whereas SMAD5-AS1 overexpression could lead to the opposite effects in vitro and in vivo. Bioinformatics analysis and luciferase assays revealed that miR-135b-5p was a direct target of SMAD5-AS1, which was validated by dual-luciferase reporter assays, AGO2-RIP, RNA pull-down assay, and rescue experiments. Also, dual-luciferase reporter assays and rescue experiments demonstrated that miR-135b-5p targeted the adenomatous polyposis coli (APC) gene directly. SMAD5-AS1/miR-135b-5p inhibits the cell proliferation via inactivating the classic Wnt/β-catenin pathway in the form of APC dependency. Our results indicated that SMAD5-AS1 inhibits DLBCL proliferation by sponging miR-135b-5p to up-regulate APC expression and inactivate classic Wnt/β-catenin pathway, suggesting that SMAD5-AS1 may act as a potential biomarker and therapeutic target for DLBCL.

Neutrophils are a significant population of infiltrated immune cells in the tumor microenvironment. Neutrophil extracellular traps (NETs) are implicated in the biological behavior of many malignant tumors. NETs can be degraded into soluble nucleosomes, leading to the release of fragments containing DNA and granule proteins into the peripheral blood (PB). Using human gastric cancer (GC) biopsies and PB samples, we investigated the specific value of NETs in GC from a clinical perspective. In summary, the formation of NETs was discovered in the tissue microenvironment and PB of GC patients. The amounts of NETs and neutrophil accumulation decreased from tumor tissue to paratumor tissue. In addition, the level of NETs in the PB gradually declined through the following patient populations: advanced disease patients, preoperative patients, postoperative patients, benign disease patients, and healthy controls. The levels of NETs in the plasma and serum were significantly correlated. As a serum biomarker, NETs had a better diagnostic value than carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in GC. The neutrophil count and neutrophil to lymphocyte ratio (NLR) were significantly associated with the level of NETs in the PB. The existence of lymph node metastasis indicated a high level of NETs in the serum. Moreover, the level of NETs in the PB was inversely correlated with short-term efficacy in GC patients who had received advanced first-line treatment. The higher baseline level of NETs in the PB of patients with negative HER2 status was correlated with worse progression-free survival (PFS). And the level of NETs in the PB was a unfavorable independent prognostic factor for PFS in patients with advanced GC who had received first-line treatment. Thus, NETs have novel diagnostic, therapeutic predictive, and prognostic value in GC patients.

Purpose: This clinical study sought to determine whether the levels of inflammatory markers predicted the survival of advanced gastric cancer (AGC) patients who underwent anti-programmed death 1 (PD-1) therapy.Methods: Using AGC patient plasma samples and baseline characteristics, we investigated the specific value of inflammatory markers in AGC from a clinical perspective in immunotherapy.Results: One hundred and six patients with AGC who underwent anti-PD-1 therapy were enrolled in this study between 20 July 2019 and 16 March 2021. A significant decrease in NLR, dNLR, and SII was noticed among the PR (P=0.023; P=0.036; P=0.001), SD (P=0.048; P=0.022; P=0.023), ORR (P=0.021; P=0.032; P=0.001), and DCR (P=0.003; P=0.001; P<0.001) groups after anti-PD-1 therapy. Additionally, a significant decline of PLR was also observed in PR (P=0.010), ORR (P=0.007), and DCR (P=0.005) after anti-PD-1 therapy. Only MLR levels increased significantly at the time of anti-PD-1 immunotherapy the failure compared to baseline (P=0.039). And statistically significant elevations in NLR (P=0.001), MLR (P=0.020), dNLR (P=0.002), and SII (P=0.019) were found in failure of anti-PD-1 treatment compared to optimal efficacy in AGC patients. In first-line treatment, the number of metastatic sites (P=0.001) was an independent prognostic factor for PFS, and peritoneal metastases (P=0.004) and platelet-to-lymphocyte ratio (PLR) level (P=0.014) were independent prognostic predictors of OS according to Cox regression analysis. In second-line or posterior treatment, the number of metastatic sites (P=0.007), ECOG (P=0.011), and PLR level (P=0.033) were independent prognostic factors for PFS in AGC patients, and the number of metastatic sites (P=0.003), differentiation (P=0.030), and NLR level (P<0.001) were independent prognostic factors for OS according to Cox regression analysis.Conclusions: NLR, PLR, MLR, dNLR, and SII can reflect the short-term efficacy of immunotherapy in patients who underwent anti-PD-1 therapy with AGC. PLR is an independent prognostic factor for OS in AGC patients receiving first-line immunotherapy and PFS in those receiving second-line or posterior immunotherapy. And NLR was an independent prognostic factor for OS in AGC patients receiving second-line or posterior immunotherapy. The number of metastatic sites was significantly associated with the prognosis of AGC patients who received immunotherapy.

As the predominant host defense against pathogens, neutrophil extracellular traps (NETs) have attracted increasing attention due to their vital roles in infectious inflammation in the past few years. Interestingly, NETs also play important roles in noninfectious conditions, such as rheumatism and cancer. The process of NETs formation can be regulated and the form of cell death accompanied by the formation of NETs is regarded as “NETosis”. A large amount of evidence has confirmed that many stimuli can facilitate the release of NETs from neutrophils. Furthermore, it has been illustrated that NETs promote tumor growth and progression via many molecular pathways. Meanwhile, NETs also can promote metastasis in many kinds of cancers based on multiple studies. In addition, some researchs have found that NETs can promote coagulation and cancer-associated thrombosis. In the present review, it will highlight how NETosis, which is stimulated by various stimuli and signaling pathways, affects cancer biological behaviors via NETs. Given their crucial roles in cancer, NETs will become possible therapeutic targets for inhibiting proliferation, metastasis and thrombosis in cancer patients.

Objective: To explore the altered expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and cell proliferation index (Ki-67) in primary and metastatic breast cancer lesions and the correlation between the primary tumor size, lymph node metastasis, Tumor Node Metastasis (TNM) stage, molecular typing, and disease-free survival (DFS) and their clinical significance.Methods: A retrospective analysis was conducted on the clinical data of 130 patients with metastatic breast cancer biopsy admitted to the Cancer Center of the Second Affiliated Hospital of Anhui Medical University in Hefei, China, from 2014–2019. The altered expression of ER, PR, HER2, and Ki-67 in primary and metastatic lesions of breast cancer was analyzed with respect to the site of metastasis, size of the primary tumor, lymph node metastasis, disease progression, and prognosis.Results: The inconsistent expression rates of ER, PR, HER2, and Ki-67 in primary and metastatic lesions were 47.69%, 51.54%, 28.10%, and 29.23%, respectively. The size of the primary lesion was not, but that accompanied by lymph node metastasis was related to the altered receptor expression. Patients with positive ER and PR expression in both primary and metastatic lesions had the longest DFS, while those with negative expression had the shortest DFS. Also, changes in HER2 expression in primary and metastatic lesions were not associated with DFS. Patients with low expression of Ki-67 in both primary and metastatic lesions had the longest DFS, while patients with high expression had the shortest DFS.Conclusion: Heterogeneity was detected in the expression levels of ER, PR, HER2, and Ki-67 in the primary and metastatic breast cancer lesions, which has a guiding significance for the treatment and prognosis of patients.

Purpose: This study aims to assess the prognostic value of inflammatory markers and clinical features in advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients receiving anti-programmed death 1 (PD-1) treatment.Methods: Based on receiver operating characteristic curve (ROC) analysis, Youden’s indexes were applied to determine the cut-off values for inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocye ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Wilcoxon test was conducted to evaluate the changes in above inflammatory markers. Kaplan-Meier method was utilized to estimate progression-free survival (PFS) and overall survival (OS), and the Log-rank test was used to compare the different survival between groups. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of inflammatory markers and clinical features.Results: 162 advanced or metastatic ESCC patients receiving anti-PD-1 treatment were enrolled in this retrospective study. The cut-off values of NLR, dNLR, MLR, PLR, and SII were 4.748, 2.214, 0.309, 250.505, and 887.895, respectively. NLR, dNLR, PLR, and SII declined significantly among the partial response (PR) (P<0.001, P<0.001, P=0.036, P<0.001), objective response rate (ORR) (P<0.001, P<0.001, P=0.036, P<0.001), and disease control rate (DCR) (P<0.001, P<0.001, P=0.038, P<0.001) groups, respectively. Significant increases were found in NLR (P<0.001), dNLR (P<0.001), MLR (P=0.001), and SII (P=0.024) when anti-PD-1 treatment failed. Multivariate Cox regression analysis indicated that NLR (P<0.001, P=0.002), lymph node metastasis (P=0.013, P=0.001), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (P=0.008, P=0.002), and treatment lines (P=0.037, P=0.048) were significant prognostic indicators of PFS and OS. Additionally, SII (P=0.016) was also significantly related to OS in ESCC patients. The risk score model showed that low risk patients prolonged PFS and OS than those with middle or high risk (P<0.001, P<0.001).Conclusion: Inflammatory markers can reflect short-term outcomes of anti-PD-1 treatment for ESCC patients. NLR, lymph node metastases, ECOG PS, and treatment lines are significant prognostic indicators for PFS and OS. And the risk score model constructed based on the above factors has favourable prognostic predictive value.