Prognostic significance of pretreatment plasma D-dimer levels in patients with spinal chordoma: a retrospective cohort study.

PURPOSE: Plasma D-dimer levels, a marker of hypercoagulation, have not only been used as an indicator for cascaded reaction in the coagulation process but are also reported to be an underlying biomarker in several types of cancers. This retrospective cohort study was designed to evaluate the prognostic value of preoperative plasma D-dimer level in patients with spinal chordoma. METHODS: We enrolled 224 patients who underwent surgery for spinal chordoma between 2002 and 2015 at Changzheng Orthopedic Oncology Center. Preoperative clinical parameters were recorded and evaluated by univariate and multivariate Cox regression models. The correlation between preoperative plasma D-dimer levels and survival was assessed using the Kaplan-Meier method. RESULTS: The optimal cutoff value of pretreatment D-dimer was 840 µg/L determined by X-tile. DFS (disease-free survival) was 64.7% and OS (overall survival) was 75% in the cohort. Multivariate Cox regression model identified D-dimer level as an independent prognostic factor of DFS and OS, as well as treatment history, preoperative Karnofsky Performance Scale, preoperative Frankel score, pathology classification and adjuvant radiotherapy (p < 0.05). In addition, D-dimer level may also be an effective supplement for defining tumor Enneking staging (p < 0.05). CONCLUSIONS: Higher pretreatment plasma D-dimer level was associated with a poor prognosis in chordoma and could be used as an independent prognostic factor for the survival of the patients with spinal chordoma. With supplementation of D-dimer level, Enneking stage may be more able to accurate stratify individualized risk and determine clinical management. These slides can be retrieved under Electronic Supplementary Material.

Genome-scale analysis to identify prognostic markers and predict the survival of lung adenocarcinoma.

Lung cancer is one of the most malignant cancers worldwide, and lung adenocarcinoma (LAC) remains the most common histologic subtype. However, the functional significance of RNA expression-based prognosis prediction in LAC is still unclear and needs to be further studied. By utilizing the Cox multivariate regression, we established a risk score staging system to predict the outcome of patients with LAC and subsequently identified 10 genes, including PTPRH, OGFRP1, LDHA, AL365203.1, LINC02178, AL512488.1, LINC01312, AL353746.1, DRAXINP1, and LINC02310, which were closely related to the prognosis of patients with LAC. The identified genes allowed us to classify patients into high-risk group with poor outcome and low-risk group with better outcome. Compared with other clinical factors, the risk score performs better in predicting the outcome of LAC patients. We used Gene-Set Enrichment Analysis to identify the differences between the 2 groups in biological pathways. In conclusion, we identified 10 genes by utilizing Cox regression model and developed a risk staging model for LAC, which might prove significant for the clinical management of LAC patients.

The Schlafen family: complex roles in different cell types and virus replication.

The Schlafen (slfn) gene family members express broadly, but the research has mainly focused on human slfn (h-slfn) and mouse slfn (m-slfn). The slfn members can be divided into three groups, and each group has its own characteristics and functions. Although the effects of slfns are still poorly understood, it has been confirmed that slfns are involved in the defense of immune system and regulate immune cells' proliferation and differentiation. In some malignant tumors, the slfn proteins can inhibit the growth and invasion of cancer cells, promote cancer cells sensibility to chemotherapeutics, and can be a promising new therapeutic target. In addition, the slfn proteins also disturb replication and virulence of viruses. In this review, we summarize the characteristics of the Schlafen family's structures and functions with the aim to achieve a more comprehensive understanding of slfns.

The epithelial to mesenchymal transition (EMT) and cancer stem cells: implication for treatment resistance in pancreatic cancer.

The mechanical properties of epithelial to mesenchymal transition (EMT) and a pancreatic cancer subpopulation with stem cell properties have been increasingly recognized as potent modulators of the effective of therapy. In particular, pancreatic cancer stem cells (PCSCs) are functionally important during tumor relapse and therapy resistance. In this review we have surveyed recent advances in the role of EMT and PCSCs in tumor progression, metastasis and treatment resistance, and the mechanisms of integrated with biochemical signals and the underlying pathways involved in treatment resistance of pancreatic cancer. These findings highlight the importance of confirming stem-cells markers and complex molecular signaling pathways controlling EMT and cancer stem cells in pancreatic cancer during tumor formation, progression, and response to therapy.

ISG15 Promotes Progression and Gemcitabine Resistance of Pancreatic Cancer Cells Through ATG7.

Chemoresistance is an obstacle of improving pancreatic cancer (PC) prognosis. However, the biological function of ISG15 in PC and whether it correlates with the resistance to chemotherapy are still unknown. Here, we aimed to reveal the clinical significance of ISG15 in PC and its regulatory mechanism in cancer progression and resistance to therapy. The level of ISG15, a protein involved in post-translational modifications, is elevated in PC tissues. Clinically, higher ISG15 expression correlates with higher PC grades, stronger resistance to treatment and poorer prognosis. Moreover, ISG15 promotes the proliferation, migration, invasion, colony formation of PC cells and resistance to Gemcitabine, a classic chemotherapeutics for PC, both in vitro and in vivo. ISG15 promotes progression and resistance to therapy in PC cells by binding to ATG7, reducing its degradation, and thereby leading to enhanced autophagy in PC cells. ISG15 may be used as both a potential diagnosis marker and sensitizer for chemotherapeutics such as Gemcitabine during PC intervention.

Selective activation of STAT3 and STAT5 dictates the fate of myeloid progenitor cells.

The molecular programs that govern the directed differentiation of myeloid progenitor cells are still poorly defined. Using a previously established immortalized, phenotypically normal myeloid progenitor cell model mEB8-ER, we unveil a new mechanism mediated by STAT5 and STAT3 at a bifurcation point of myeloid progenitor cell-fate specification. We find that myeloid progenitor cells can spontaneously differentiate into neutrophils with a basal level of STAT3 phosphorylation, which is enhanced by G-CSF treatment or STAT3 over-expression, leading to elevated neutrophil differentiation. Reduced STAT3 phosphorylation caused by GM-CSF treatment, STAT3 specific inhibitor, or STAT3 depletion leads to attenuated myeloid differentiation into neutrophils, while elevating differentiation into monocytes/macrophages. In contrast, STAT5 appears to have an antagonistic function to STAT3. When activated by GM-CSF, STAT5 promotes myeloid differentiation into monocytes/macrophages but inhibits neutrophil differentiation. At the mechanistic level, GM-CSF activates STAT5 to up-regulate SOCS3, which attenuates STAT3 phosphorylation and consequently neutrophil differentiation, while enhancing monocyte/macrophage differentiation. Furthermore, inhibition of STAT5 and STAT3 in primary myeloid progenitors recapitulates the results from the mEB8-ER model. Together, our findings provide new mechanistic insights into myeloid differentiation and may prove useful for the diagnosis and treatment of diseases related to abnormal myeloid differentiation.

The prognostic value and biological functions of HFM1 in breast cancer.

Aim: HFM1 has been reported to be associated with meiosis and ovarian insufficiency, but its role in tumors remains unknown. This study aims to explore the functions and potential mechanism of HFM1 in breast cancer. Methods: Several databases, protein-protein interactions, gene ontology and the Kyoto Encyclopedia of Genes and Genomes were used for bioinformatic analysis. Tissue microarrays and cell viability assays were used to detect the expression of HFM1 and tamoxifen resistance, respectively. Results: HFM1 was downregulated in breast cancer with poor prognosis and may modulate DNA damage repair pathways and immune infiltration. Moreover, HFM1 may mediate ovarian steroidogenesis and participate in tamoxifen resistance of estrogen receptor-positive breast cancer cells. Conclusion: We presented a first study on biological functions and potential mechanisms of HFM1 in cancers.

The role and function of the protein HFM1 in tumors remains unknown. We explored the functions and potential mechanism of HFM1 in breast cancer through several known databases, clinical samples and cell experiments. We found that HFM1 was downregulated in breast cancer with a poor prognosis. HFM1 may mediate ovarian steroidogenesis and participate in tamoxifen resistance of estrogen receptor-positive breast cancer cells. Here we first put forward the relationship between HFM1 and the prognosis of breast cancer, and provided relevant clues for mechanism exploration.

Roles of the RANKL-RANK Axis in Immunity-Implications for Pathogenesis and Treatment of Bone Metastasis.

A substantial amount patients with cancer will develop bone metastases, with 70% of metastatic prostate and breast cancer patients harboring bone metastasis. Despite advancements in systemic therapies for advanced cancer, survival remains poor for those with bone metastases. The interaction between bone cells and the immune system contributes to a better understanding of the role that the immune system plays in the bone metastasis of cancer. The immune and bone systems share various molecules, including transcription factors, signaling molecules, and membrane receptors, which can stimulate the differentiation and activation of bone-resorbing osteoclasts. The process of cancer metastasis to bone, which deregulates bone turnover and results in bone loss and skeletal-related events (SREs), is also controlled by primary cancer-related factors that modulate the intratumoral microenvironment as well as cellular immune process. The nuclear factor kappa B ligand (RANKL) and the receptor activator of nuclear factor kappa B (RANK) are key regulators of osteoclast development, bone metabolism, lymph node development, and T-cell/dendritic cell communication. RANKL is an osteoclastogenic cytokine that links the bone and the immune system. In this review, we highlight the role of RANKL and RANK in the immune microenvironment and bone metastases and review data on the role of the regulatory mechanism of immunity in bone metastases, which could be verified through clinical efficacy of RANKL inhibitors for cancer patients with bone metastases. With the discovery of the specific role of RANK signaling in osteoclastogenesis, the humanized monoclonal antibody against RANKL, such as denosumab, was available to prevent bone loss, SREs, and bone metastases, providing a unique opportunity to target RANKL/RANK as a future strategy to prevent bone metastases.

Erratum: Metformin induces cell cycle arrest, apoptosis and autophagy through ROS/JNK signaling pathway in human osteosarcoma: Erratum.

[This corrects the article DOI: 10.7150/ijbs.33787.].

Failure Patterns of Recurrence and Metastasis After Intensity-Modulated Radiotherapy in Patients With Nasopharyngeal Carcinoma: Results of a Multicentric Clinical Study.

PURPOSE: This study aimed to explore factors associated with recurrence and metastasis after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) and provide evidence for NPC treatment. METHODS: We retrospectively analysed the treatment dose and survival outcomes of 645 patients with nasopharyngeal carcinoma without distant metastases treated with IMRT for the first time at three treatment centres in the Guangxi Zhuang Autonomous Region, China, between January 2009 and December 2012. RESULTS: There were 9.3% of patients (60/645) had recurrence and 17.5% (113/645) had distant metastasis 5 years after treatment. The 1-year, 3-year and 5-year local recurrence rates were 0.9%, 6.5% and 9.0% respectively. And the 1-year, 3-year and 5-year distant metastasis rates were 3.4%, 10% and 17.2%, respectively. In the 60 patients with recurrence, the in-field, marginal-field, and out-field recurrence rates were 93.3% (56/60), 5.0% (3/60) and 1.7% (1/60), respectively. Recurrence failures occurring within the first three years after treatment accounted for 81.7% (49/60). In the 113 patients with metastasis, the size of the cervical lymph node, the presence of lower cervical lymph node metastasis, the residual cervical lymph node size and the time of residual cervical lymph node complete response (CR) were independent prognostic factors for DMFS (P <0.05). CONCLUSION: Most recurrences occured in the first three years after IMRT. In-field recurrence was the most common pattern for loco-regional failure of NPC treatment. The risk of distant metastasis was positively correlated with higher N stage, lower neck nodal metastasis, larger size of cervical lymph nodes, and longer time to response for residual NPC in cervical adenopathy.

Metformin induces cell cycle arrest, apoptosis and autophagy through ROS/JNK signaling pathway in human osteosarcoma.

Metformin, an ancient drug commonly used for treating type II diabetes, has been associated to anti-cancer capacity in a variety of developing cancers, though the mechanism remains elusive. Here, we aimed to examine the inhibitory effect of metformin in osteosarcoma. Herein, we demonstrated that metformin treatment blocked proliferation progression by causing accumulation of G2/M phase in U2OS and 143B cells. Furthermore, metformin treatment triggered programmed cell death process in osteosarcoma cell lines. Further research indicated the induction of apoptosis and autophagy triggered by metformin could remarkably attenuate after the treatment of ROS scavenger NAC and JNK inhibitor SP600125. Additionally, our results showed that NAC-suppressed JNK/c-Jun signaling pathway could have been activated through metformin treatment. Lastly, metformin could inhibit osteosarcoma growth under safe dose in vivo. Thus, we propose that metformin could induce cell cycle arrest as well as programmed cell death, including apoptosis and autophagy, through ROS-dependent JNK/c-Jun cascade in human osteosarcoma. This metformin-induced pathway provides further insights into its antitumor potential molecular mechanism and illuminates potential cancer targets for osteosarcoma.

NMIIA promotes tumor growth and metastasis by activating the Wnt/ß-catenin signaling pathway and EMT in pancreatic cancer.

Non-muscle myosin IIA (NMIIA) protein plays an important role in cell cytokinesis and cell migration. The role and underlying regulatory mechanisms of NMIIA in pancreatic cancer (PC) remain elusive. We found that NMIIA is highly expressed in PC tissues and contributes to PC poor progression by using open microarray datasets from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and PC tissue arrays. NMIIA regulates ß-catenin mediated EMT to promote the proliferation, migration, invasion, and sphere formation of PC cells in vitro and in vivo. NMIIA controls the ß-catenin transcriptional activity by interacting with ß-catenin. Moreover, MEK/ERK signaling is critical in MLC2 (Ser19) phosphorylation, which can mediate NMIIA activity and regulate Wnt/ß-catenin signaling. These findings highlight the significance of NMIIA in tumor regression and implicate NMIIA as a promising candidate for PC treatment.

The MTOR signaling pathway regulates macrophage differentiation from mouse myeloid progenitors by inhibiting autophagy.

Understanding of the mechanism for myeloid differentiation provides important insights into the hematopoietic developmental processes. By using an ESC-derived myeloid progenitor cell model, we found that CSF2/GM-CSF triggered macrophage differentiation and activation of the MTOR signaling pathway. Activation or inhibition of the MTOR signaling enhanced or attenuated macrophage differentiation, respectively, suggesting a critical function. We further showed that macroautophagy/autophagy was inhibited with the addition of CSF2. Furthermore, pharmacological inhibition and genetic modification of autophagy enhanced macrophage differentiation and rescued the inhibitory effect on differentiation caused by MTOR inhibition. Thus, the MTOR signaling pathway regulates macrophage differentiation of myeloid progenitors by inhibiting autophagy. Our results provide new insights into the mechanisms for myeloid differentiation and may prove useful for therapeutic applications of hematopoietic and myeloid progenitor cells. Abbreviations: 2-DG: 2-deoxy-D-glucose; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; BM: bone marrow; CQ: chloroquine; ECAR: extracellular acidification rate; ESC: embryonic stem cell; CSF2/GM-CSF: colony stimulating factor 2; CSF3/G-CSF: colony stimulating factor 3; HPC: hematopoietic progenitor cell; ITGAM/CD11b: integrin alpha M; LPS: lipopolysaccharide; MFI: median fluorescence intensity; MTOR: mechanistic target of rapamycin kinase; RPS6KB1/p70S6K1: ribosomal protein S6 kinase, polypeptide 1; shRNA: short hairpin RNA; SQSTM1/p62: sequestosome 1.

Prognostic role of serum total cholesterol and high-density lipoprotein cholesterol in cancer survivors: A systematic review and meta-analysis.

BACKGROUND: The alterations of lipid profile in cancer has been reported to be associated with cancer development. However, the prognostic value of serum lipid markers level in cancer is currently under debate. Here we performed a meta-analysis to investigate the prognostic significance of serum blood total cholesterol (TC), Triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) for cancer. METHODS: We systematically searched in PubMed and EMBASE for follow-up studies to evaluate the association between blood TC, TG, HDL-C, LDL-C and overall survival (OS) or disease-free survival (DFS) in patients with cancer. Pooled hazard ratio (HR) and 95% CIs were pooled using the random models. Subgroup and sensitivity analyses were also performed. RESULTS: Twenty-six studies including 24655 individuals were identified. For patients with higher TC before diagnosis, the summary HR were 0.82 (95% CI 0.75-0.90) for OS, 0.920 (95% CI, 0.849-0.997) for DFS. Patients with higher HDL-C had a 37% reduced risk of death compared with lower HDL-C (HR 0.63, 95%CI 0.47-0.86, P<0.001). As for DFS, patients with higher HDL-C level had the risk of disease relapse reduced by 35% (HR 0.65, 95% CI, 0.48-0.89, P<0.001) compared with patients with lower levels. CONCLUSIONS: After pooled analysis, only TC and HDL-C were significantly associated with cancer survival. Our findings demonstrate for the first time that serum TC and HDL-C was identified as a protective factor for overall survival in cancer patients.

Intensity-modulated radiotherapy combined with endostar has similar efficacy but weaker acute adverse reactions than IMRT combined with chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma.

The present study is to compare the efficacy and adverse effects of intensity-modulated radiotherapy (IMRT) combined with endostar and IMRT combined with concurrent chemotherapy on locally advanced nasopharyngeal carcinoma (NPC).A total of 23 patients with stage III-IVa NPC were included in the present study, and randomly divided into experimental group (10 cases treated with IMRT + endostar) and control group (13 cases treated with IMRT + chemotherapy of cis-dichlorodiamineplatinum). Endostar was intravenously administered from the first day of IMRT. The patients received a total of 2 cycles (14 days each) separating by a 7-day interval.IMRT combined with endostar did not have significantly different recent efficacy compared with IMRT combined with chemotherapy. IMRT combined with endostar and IMRT combined with chemotherapy had 2-year overall survival (OS) rates of 100.0% and 69.6%, respectively, without significant difference between each other (χ = 1.446, P = .299). The 2-year local relapse-free survival (LRFS) of the 2 groups were 100.0% and 81.3%, respectively, without significant difference between each other (χ = 1.000, P = .317). The 2-year distant metastasis-free survival (DMFS) of the 2 groups were 100.0% and 73.5% (χ = 1.591, P = .207), respectively. The 2-year progression-free survival (PFS) of the 2 groups were 100.0% and 67.3% (χ = 2.164, P = .141), respectively. However, the cumulative survival curves of OS, LRFS, DMFS, and PFS were separated between the 2 groups. The result that IMRT combined with endostar did not have significantly different long-term efficacy than IMRT combined with chemotherapy probably due to limited case number and short follow-up time. IMRT combined with endostar resulted in significantly lower grades of leucopenia, nausea/vomiting, weight loss, and oral mucositis compared with IMRT combined with chemotherapy. The grades of late adverse reactions of IMRT combined with endostar were not different from those of IMRT combined with chemotherapy.The present study demonstrates that, compared with IMRT combined with chemotherapy, IMRT combined with endostar has similar efficacy in the treatment of locally advanced NPC, but significantly weaker acute adverse reactions, which improve the life quality of NPC patients.

Platelet-to-lymphocyte ratio in advanced Cancer: Review and meta-analysis.

BACKGROUND: Inflammation biomarkers have been introduced into clinical practice for risk-rating in treatment of patients with cancer. We aimed to confirm the prognostic role of platelet-to-lymphocyte ratio (PLR) as a powerful biomarker for patients with advanced cancer. METHOD: A systematic literature search was conducted through PubMed, Embase and Web of Science databases for studies on advanced tumors. Research articles that analyzed the PLR and hazard ratios (HR) in patients with overall survival (OS) or progression-free survival (PFS) data were involved. Two authors assessed the eligibility of trials and extracted data independently. Meta-analyses were performed with random-effect models. Data heterogeneity was calculated with the I2 method. RESULTS: Thirty-three eligible cohort studies including 8215 patients were further analyzed. Elevated PLR was associated with reduced OS (HR = 1.45, 95% CI, 1.31-1.61, p < 0.001) and PFS (HR = 1.73, 95% CI, 1.31-2.29, p < 0.001) in patients with advanced cancer. A extreme result was observed in a subgroup analysis in metastatic renal cancer with the worst OS (HR = 2.47, 95% CI, 1.32-4.62, p = .005) and PFS (HR = 3.89, 95% CI, 1.23-12.28, p = 0.021). CONCLUSIONS: Patients with high pretreatment blood PLR level have poor OS and PFS. Further investigations are needed to explore the underlying mechanisms.

NLRP12 Promotes Mouse Neutrophil Differentiation through Regulation of Non-canonical NF-κB and MAPKERK1/2 Signaling.

Neutrophils are the most important component of the innate immune system. Mechanistic understanding of the mechanism underlying neutrophil differentiation remains elusive. Using genome-wide RNA-seq, we identified genes whose expression is dramatically up-regulated during neutrophil differentiation. Among them is nucleotide-binding leucine-rich repeat and pyrindomain-containing receptor 12 (NLRP12), which plays a role in immune inflammatory responses. Genetic ablation of NLRP12 suppresses NF-κB inducing kinase (NIK) stabilization, RelB nuclear translocation and neutrophil differentiation in vitro. At a mechanistic level, NLRP12 inhibits the activity of mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK1/2), relieves ERK1/2 suppression of NIK protein levels. Thus, NLRP12 enhances noncanonical NF-κB signaling through inhibition of ERK1/2 signaling, thereby promoting neutrophil differentiation.

A novel N staging system for NPC based on IMRT and RTOG guidelines for lymph node levels: Results of a prospective multicentric clinical study.

The present study aimed to investigate the cervical lymph node metastasis of nasopharyngeal carcinoma (NPC) and to establish a novel N staging standard for NPC, based on intensity modulated radiation therapy (IMRT) via a prospective multicenter clinical trial. Between January 2006 and December 2009, a total of 492 patients with NPC without distant metastasis were included in the present study. All patients were treated with IMRT. According to Radiation Therapy Oncology Group division standards, the present study proposed a novel N staging system following the review of magnetic resonance images in comparison with the 7th edition of Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system. Retropharyngeal lymph nodes, cervical lymph node level and cervical lymph node laterality were independent prognostic factors used in multivariate analyses. According to the results of the risk variety, the present study suggested that the novel N staging system included: N0 (no lymph node metastasis), N1 [retropharyngeal or/and unilateral upper cervical (I, II, III, Va, VIIb, VIII, IX and X regions) lymph node metastasis], N2 [bilateral upper cervical (I, II, III, Va, VIIb, VIII, IX and X regions) lymph node metastasis] and N3 (lymph node metastasis in IVa and Vb regions and their lower regions). The novel N staging system proposed in the present study performs better in risk difference and distribution balance. Furthermore, the differences of 5-year curves of distant metastasis-free survival and overall survival had greater statistically significant differences compared with the 7th edition of the UICC/AJCC staging system. The present study suggested a novel N staging system for cervical lymph node metastasis of NPC, which may predict the prognosis of patients with NPC in a more objective and accurate way.

Autophagy inhibition enhances celecoxib-induced apoptosis in osteosarcoma.

Osteosarcoma (OS) is the most prevalent bone malignancy in childhood and adolescence, with highly aggressive and early systemic metastases. Here, we reported that celecoxib, a selective COX-2 inhibitor in the NSAID class, exhibits strong antitumor activity in dose dependent manner in two OS cell lines-143B and U2OS. We showed that celecoxib inhibits OS cell growth, causes G0/G1-phase arrest, modulates apoptosis and autophagy and reduces migration in OS cells. In addition, the results of fluorescent mitochondrial probe JC-1 test indicated that the mitochondrial pathway mediates celecoxib-induced apoptosis. Significantly, the autophagy inhibitor CQ combined with celecoxib causes greater cell proliferation inhibition and apoptosis. Pharmacologic inhibition of autophagy with another potent autophagy inhibitor SAR405 also enhances celecoxib-mediated suppression of cell viability. These results were confirmed with shRNAs targeting the autophagy-related gene Atg5. In OS tumor xenografts in vivo, celecoxib also presents antitumor activity. Taken together, our results shed light on the function and mechanism of antitumor action of celecoxib for treatment of OS patients.

Prognostic value of pretreatment plasma D-dimer levels in patients with diffuse large B cell lymphoma (DLBCL).

BACKGROUND: We assessed the prognostic significance of D-dimer in patients of diffuse large B cell lymphoma (DLBCL). METHODS: We performed a retrospective study including 254 patients who were newly diagnosed DLBCL. X-tile was used to generate a cutoff value for D-dimer. Both univariate screen by Cox proportional hazard model and multivariable analysis by Cox regression model were used to assess the impact of pretreatment D-dimer levels on the overall survival (OS). RESULT: According to X-tile, the optimal cut-off value of D-dimer for prediction of survival was set as 1.6 µg/mL, and a D-dimer level ≥ 1.6 µg/mL was significantly associated with poor overall survival (OS) (OS: 31.7 vs. 79.1%, P < 0.001). In multivariable analysis, it was found that a higher D-dimer level was an independent predictor for worse OS (Hazard ratio (HR): 3.594 95% Confidence interval (CI): 2.296-5.267, P < 0.001). In subgroup analysis of International Prognostic Index (IPI), survival of low-risk and intermediate-risk group with a D-dimer level ≥ 1.6 µg/mL were both similar to that of the high-risk group (OS: 31.6 vs. 36.5%, P = 0.957; OS: 38.0 vs. 36.5%, P = 0.758). In addition, among patients treated with surgery, those with higher D-dimer had substantially worse survival than that with lower D-dimer (OS: 27.0 vs. 84.5%, P < 0.001). CONCLUSION: Pretreatment D-dimer is a simple but effective predictor of survival among patients with DLBCL.