Evolution of lasR mutants in polymorphic Pseudomonas aeruginosa populations facilitates chronic infection of the lung.

Chronic infection with the bacterial pathogen Pseudomonas aeruginosa often leads to coexistence of heterogeneous populations carrying diverse mutations. In particular, loss-of-function mutations affecting the quorum-sensing regulator LasR are often found in bacteria isolated from patients with lung chronic infection and cystic fibrosis. Here, we study the evolutionary dynamics of polymorphic P. aeruginosa populations using isolates longitudinally collected from patients with chronic obstructive pulmonary disease (COPD). We find that isolates deficient in production of different sharable extracellular products are sequentially selected in COPD airways, and lasR mutants appear to be selected first due to their quorum-sensing defects. Polymorphic populations including lasR mutants display survival advantages in animal models of infection and modulate immune responses. Our study sheds light on the multistage evolution of P. aeruginosa populations during their adaptation to host lungs.

Involvement of the E3 ubiquitin ligase Cblb in host defense and evaluation of transcriptome during Trueperella pyogenes infection.

Trueperella pyogenes (T. pyogenes) is a versatile and ingenious bacterium that causes severe suppurative injuries in lots of economically important ruminants. The underlying pathogenesis of T. pyogenes infection remains poorly understood. In the current study, we performed transcriptome sequencing of mouse blood tissue infected with T. pyogenes. A total of 36.73 G clean data were collected, and 136 differentially expressed genes were obtained in the infection group compared to the control group. In addition, we found that the E3 ubiquitin ligase Cblb exhibited significant upregulation in the infection groups compared to the control group. Mechanistically, T. pyogenes infection markedly enhanced the expression of Cblb and regulated the host defense response. Inhibiting Cblb expression with Cblb siRNA impaired the inflammatory response and reduced the effect of phagocytosis in RAW264.7 murine macrophages. Intriguingly, overexpression of Cblb induced a strong inflammatory response and enhanced phagocytosis against T. pyogenes infection in macrophages. More importantly, the overexpression of Cblb significantly reduced the bacterial load and protected mice from the T. pyogenes infections. Therefore, our findings reveal that Cblb is a novel and potential regulator in response to T. pyogenes infection and shed new light on the development of promising treatments against T. pyogenes-related diseases.

Sintilimab combined with chemotherapy successfully treated a patient with advanced submandibular gland tumor.

Primary submandibular gland tumors are relatively rare. Due to its low incidence and broad spectrum phenotypic, biological and clinical heterogeneity types, a wide range of options have been developed to treat this tumor. To date, however, efficacious standard treatment regimens are lacking. Here, the authors present a case of a patient with an advanced submandibular gland tumor. Histological and imaging results diagnosed the case as stage IV submandibular gland adenocarcinoma with multiple metastases. The patient was subjected to systemic platinum-based chemotherapy combined with sintilimab. A primary lesion complete response was observed after six cycles of treatment. This case affirms the efficacy of the PD-1 inhibitor sintilimab combined with platinum-based chemotherapy as a first-line treatment for advanced submandibular gland tumors.

Primary submandibular gland tumors are very uncommon. There is a lack of standard treatment plans due to the low incidence and diverse clinical situations. The authors report a case of an advanced submandibular gland tumor patient who received platinum-based chemotherapy combined with sintilimab as the initial treatment plan. The tumor and multiple lung metastases significantly shrank after six cycles of treatment. This case indicates the regimen is effective for advanced submandibular gland tumor patients.

Recent Advances in DNA Vaccines against Lung Cancer: A Mini Review.

Lung cancer is regarded as the major causes of patient death around the world. Although the novel tumor immunotherapy has made great progress in the past decades, such as utilizing immune checkpoint inhibitors or oncolytic viruses, the overall 5-year survival of patients with lung cancers is still low. Thus, development of effective vaccines to treat lung cancer is urgently required. In this regard, DNA vaccines are now considered as a promising immunotherapy strategy to activate the host immune system against lung cancer. DNA vaccines are able to induce both effective humoral and cellular immune responses, and they possess several potential advantages such as greater stability, higher safety, and being easier to manufacture compared to conventional vaccination. In the present review, we provide a global overview of the mechanism of cancer DNA vaccines and summarize the innovative neoantigens, delivery platforms, and adjuvants in lung cancer that have been investigated or approved. Importantly, we highlight the recent advance of clinical studies in the field of lung cancer DNA vaccine, focusing on their safety and efficacy, which might accelerate the personalized design of DNA vaccine against lung cancer.

Repurposing Dimetridazole and Ribavirin to disarm Pseudomonas aeruginosa virulence by targeting the quorum sensing system.

Pseudomonas aeruginosa relies on its complex cellular regulatory network to produce a series of virulence factors and to cause various acute and chronic infections in a wide range of hosts. Compared with traditional antibiotics which frequently accompany with widespread antibiotic resistance, crippling the virulence system of bacteria is expected to be a promising anti-infective strategy. In this study, Dimetridazole and Ribavirin, which had poor antibacterial activities on P. aeruginosa reference isolate PAO1 in nutrient medium but significantly inhibited the growth of P. aeruginosa PAO1 in M9-adenosine, were selected from 40 marketed compounds with similar core structure (furan, benzofuran, or flavonoids) to the acyl-homoserine lactone signals of P. aeruginosa quorum sensing (QS) system. The production of QS-controlled proteases, pyocyanin, and biofilm formation of P. aeruginosa PAO1 and the clinical isolates were significantly decreased by the presence of Dimetridazole or Ribavirin. Correspondingly, the majority of QS-activated genes in P. aeruginosa, including the key regulatory genes lasR, rhlR, and pqsR and their downstream genes, were significantly inhibited by Ribavirin or Dimetridazole, as determined by RNA-sequencing and quantitative PCR. Furthermore, the susceptibilities of drug-resistant P. aeruginosa isolates to polymyxin B, meropenem, and kanamycin were remarkably promoted by the synergistic application of Dimetridazole or Ribavirin. Finally, the treatment of Ribavirin or Dimetridazole effectively protected Caenorhabditis elegans and mice from P. aeruginosa infection. In conclusion, this study reports the antivirulence potentials of Dimetridazole and Ribavirin on P. aeruginosa and provides structural basis and methodological reference for the development of anti-pseudomonal drugs.

Nutritional risk screening in malignant tumors: a study of 375 cancer inpatients.

Malnutrition is a common complication in cancer patients. It often accelerates disease progression and affects treatment outcomes. Thus, in the early census of cancer patients, examination for possible nutritional risks and correcting potential causes of malnutrition are needed to improve patients' quality of life. Our study included 375 patients diagnosed with cancer in Henan province and analyzed the relationship between nutritional risk and indicators like age, serum albumin, serum prealbumin, serum hemoglobin, tumor stage, tumor type, and inflammatory factors. We found that age, hemoglobin, and presence of gastrointestinal tumors were independent risk factors for nutritional risk. We also found significant correlation between inflammatory factors and nutritional risk in cancer patients, so as to provide new prediction indexes for clinical management of nutritional risk and dynamic changes of nutritional status.

Polyphasic Identification and Genomic Insights of Leptothermofonsia sichuanensis gen. sp. nov., a Novel Thermophilic Cyanobacteria Within Leptolyngbyaceae.

Thermal environments are an important reservoir of thermophiles with significant ecological and biotechnological potentials. However, thermophilic isolates remain largely unrecovered from their habitats and are rarely systematically identified. In this study, we characterized using polyphasic approaches a thermophilic strain, PKUAC-SCTAE412 (E412 hereafter), recovered from Lotus Lake hot spring based in Ganzi prefecture, China. The results of 16S rRNA/16S-23S ITS phylogenies, secondary structure, and morphology comparison strongly supported that strain E412 represent a novel genus within Leptolyngbyaceae. This delineation was further confirmed by genome-based analyses [phylogenomic inference, average nucleotide/amino-acid identity, and the percentages of conserved proteins (POCP)]. Based on the botanical code, the isolate is herein delineated as Leptothermofonsia sichuanensis gen. sp. nov, a genus adjacent to recently delineated Kovacikia and Stenomitos. In addition, we successfully obtained the first complete genome of this new genus. Genomic analysis revealed its adaptations to the adverse hot spring environment and extensive molecular components related to mobile genetic elements, photosynthesis, and nitrogen metabolism. Moreover, the strain was capable of modifying the composition of its light-harvesting apparatus depending on the wavelength and photoperiod, showing chromatic adaptation capacity characteristic for T1 and T2 pigmentation types. Other physiological studies showed the strain's ability to utilize sodium bicarbonate and various sulfur compounds. The strain was also shown to be diazotrophic. Interestingly, 24.6% of annotated protein-coding genes in the E412 genome were identified as putatively acquired, hypothesizing that a large number of genes acquired through HGT might contribute to the genome expansion and habitat adaptation of those thermophilic strains. Most the HGT candidates (69.4%) were categorized as metabolic functions as suggested by the KEGG analysis. Overall, the complete genome of strain E412 provides the first insight into the genomic feature of the genus Leptothermofonsia and lays the foundation for future global ecogenomic and geogenomic studies.

Agarase cocktail from agar polysaccharide utilization loci converts homogenized Gelidium amansii into neoagarooligosaccharides.

Neoagarooligosaccharides (NAOs) are drawing more and more attention because of their numerous bioactivities, yet limited number of agarases impedes NAOs production from red algae. In this study, predicted agar polysaccharide utilization loci (agar-PUL) were firstly used as inventory for agarase. 6 agarases were identified from agar-PULs and two of them were successfully expressed and analyzed. Then enzyme cocktail (GH16-1:GH16-2:Aga50D = 2:1:1) was proved to have highest synergistic effect. Finally homogenization was applied to G. amansii and proved to be an efficient way to release agar from tissues. When liquid-to-solid ratio was 9 g/150 mL, homogenization time was 20 min, and enzyme cocktail loading was 150 U/150 mL, maximum NAOs production (90.2 mg per 9 g wet G. amansii) could be achieved. Enzyme supported one-step process (ESOP) proposed in study is environment-friendly, time saving, cost saving and none-destructive, therefore has a potential industrial application in red algae utilization.

PSMD: An extensive database for pan-species microsatellite investigation and marker development.

Microsatellites are widely distributed throughout nearly all genomes which have been extensively exploited as powerful genetic markers for diverse applications due to their high polymorphisms. Their length variations are involved in gene regulation and implicated in numerous genetic diseases even in cancers. Although much effort has been devoted in microsatellite database construction, the existing microsatellite databases still had some drawbacks, such as limited number of species, unfriendly export format, missing marker development, lack of compound microsatellites and absence of gene annotation, which seriously restricted researchers to perform downstream analysis. In order to overcome the above limitations, we developed PSMD (Pan-Species Microsatellite Database, http://big.cdu.edu.cn/psmd/) as a web-based database to facilitate researchers to easily identify microsatellites, exploit reliable molecular markers and compare microsatellite distribution pattern on genome-wide scale. In current release, PSMD comprises 678,106,741 perfect microsatellites and 43,848,943 compound microsatellites from 18,408 organisms, which covered almost all species with available genomic data. In addition to interactive browse interface, PSMD also offers a flexible filter function for users to quickly gain desired microsatellites from large data sets. PSMD allows users to export GFF3 formatted file and CSV formatted statistical file for downstream analysis. We also implemented an online tool for analysing occurrence of microsatellites with user-defined parameters. Furthermore, Primer3 was embedded to help users to design high-quality primers with customizable settings. To our knowledge, PSMD is the most extensive resource which is likely to be adopted by scientists engaged in biological, medical, environmental and agricultural research.

Degradation of MCL-1 by bufalin reverses acquired resistance to osimertinib in EGFR-mutant lung cancer.

Although osimertinib, an EGFR tyrosine kinase inhibitor, has become the standard therapy for treating non-small cell lung cancer (NSCLC) patients with EGFR-activating mutation, upregulation of MCL-1 induces acquired resistance to osimertinib. Bufalin, a natural digoxin-like ingredient isolated from a traditional Chinese medicine Chan Su, has been shown to downregulate MCL-1 in NSCLC cells. However, whether bufalin reverses this acquired resistance to osimertinib in NSCLC cells remains unclear. In this study, bufalin reduced cell viability and promoted apoptosis in osimertinib-resistant cells. Moreover, co-treatment with bufalin and osimertinib restored the sensitivity of osimertinib-resistant cells to osimertinib-induced growth regression and apoptosis in vitro and in vivo. Mechanistically, MEK/ERK-dependent MCL-1 phosphorylation and Ku70-mediated MCL-1 overexpression confer osimertinib resistance in EGFR-mutant NSCLC cells. In osimertinib-resistant cells, bufalin modulates Ku70-mediated MCL-1 degradation, but not MEK/ERK/MCL-1 signaling. In conclusion, our study suggests that bufalin eliminates resistance to osimertinib by inhibiting Ku70-mediated MCL-1 overexpression, indicating that a combination of osimertinib and bufalin could be an effective additional treatment to overcome acquired resistance to osimertinib in NSCLC cells.

Notch signaling pathway regulates CD4+CD25+CD127dim/- regulatory T cells and T helper 17 cells function in gastric cancer patients.

Regulatory T cells (Tregs) and T helper 17 (Th17) cells contribute to cancer progression and prognosis. However, regulatory factors associated with Tregs-Th17 balance were not completely understood. We previously demonstrated an immune-modulatory capacity by Notch signaling inactivation to reverse Tregs-Th17 disequilibrium in chronic hepatitis C. Thus, the aim of current study was to assess the role of Notch signaling in modulation Tregs and Th17 cells function in gastric cancer (GC) patients. A total of 51 GC patients and 18 normal controls (NCs) were enrolled. Notch1 and Notch2 mRNA expressions were semiquantified by real-time polymerase chain reaction. Tregs/Th17 percentages, transcriptional factors, and cytokines production were investigated in response to the stimulation of Notch signaling inhibitor DAPT. Both Notch1 and Notch2 mRNA expressions were elevated in GC tissues and peripheral bloods in GC patients. CD4+CD25+CD127dim/- Tregs and Th17 cells percentage was also elevated in GC patients compared with in NCs. DAPT treatment did not affect frequency of either circulating Tregs or Th17 cells, however, reduced FoxP3/RORγt mRNA expression and interleukin (IL)-35/IL-17 production in purified CD4+ T cells from GC patients. Moreover, blockade of Notch signaling also inhibited the suppressive function of purified CD4+CD25+CD127dim/- Tregs from GC patients, which presented as elevation of cellular proliferation and IL-35 secretion. The current data further provided mechanism underlying Tregs-Th17 balance in GC patients. The link between Notch signaling and Th cells might lead to a new therapeutic target for GC patients.

Cyanidin-3-O-glucoside ameliorates diabetic nephropathy through regulation of glutathione pool.

Diabetic nephropathy (DN) is a common complication of diabetes and the major cause of chronic kidney disease. Cyanidin 3-glucoside (C3G) is the most widespread anthocyanin in nature. In the present study, we aimed to investigate the possible effects of C3G on DN in db/db mice. We found that body weights and high levels of fasting blood glucose, serum insulin, C-peptide, glycosylated hemoglobin A1c, and systolic blood pressure in diabetic mice were significantly reduced by C3G. C3G also reduced the ratio of kidney to body weight and the levels of blood urea nitrogen (BUN), serum creatinine, urinary albumin content and albumin/creatinine ratio (ACR), ameliorated the pathological changes of kidneys, reduced the surface area of Bowman's capsule, glomerular tuft, Bowman's space, and decreased renal expression of collagen IV, fibronectin, transforming growth factor ß 1 (TGFß1), matrix metalloprotein 9 (MMP9) and α-smooth muscle actin (α-SMA) in db/db mice. The Lee's index, perirenal white adipose tissue weight, and high levels of blood and renal triglyceride and cholesterol were decreased by C3G. Moreover, C3G reduced systemic levels and renal expression of tumor necrosis factor ɑ (TNFɑ), IL-1ɑ, and monocyte chemotactic protein-1 (MCP-1), indicating the inhibition of inflammation. Furthermore, C3G increased glutathione (GSH) level and decreased GSSG level in kidneys of diabetic mice. The renal mRNA expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM) was increased by C3G in diabetic mice. Buthionine sulphoximine (BSO), an inhibitor of GSH synthesis, inhibited the effects of C3G on glucose metabolic dysfunction and DN. The data demonstrates that enhancement of GSH pool is involved in the renal-protective effects of C3G. Overall, C3G could be a promising therapeutic option for attenuation of diabetes and DN.

Erratum: Clinical and biological effects of tumor associated lymphocytes in the presence or absence of chemotherapy for malignant ascites in ovarian cancer patients.

[This corrects the article DOI: 10.3892/ol.2017.6635.].

Interplay between long noncoding RNA ZEB1-AS1 and miR-101/ZEB1 axis regulates proliferation and migration of colorectal cancer cells.

Long noncoding RNAs (lncRNAs) are dysregulated in many diseases. MicroRNA-101 (miR-101) functions as a tumor suppressor by directly targeting ZEB1 in various cancers. However, the potential mechanism of lncRNA ZEB1-AS1 and miR-101/ZEB1 axis in CRC remains unknown. In this study, we further investigated the potential interplay between miR-101/ZEB1 axis and lncRNA ZEB1-AS1 in colorectal cancer (CRC). Results showed that ZEB1-AS1 was upregulated in CRC tissues and cells. MiR-101 was downregulated in CRC tissues and negatively correlated with ZEB1-AS1 and ZEB1 expression levels in CRC. Functional experiments showed that, consistent with ZEB1-AS1 depletion, miR-101 overexpression and ZEB1 depletion inhibited the proliferation and migration of CRC cells. Overexpression of miR-101 partially abolished the effects of ZEB1-AS1 on the proliferation and migration of these cells. Moreover, combined ZEB1-AS1 depletion and miR-101 overexpression significantly inhibited cell proliferation and migration of the CRC cells. Hence, ZEB1-AS1 functioned as a molecular sponge for miR-101 and relieved the inhibition of ZEB1 caused by miR-101. This study revealed a novel regulatory mechanism between ZEB1-AS1 and miR-101/ZEB1 axis. The interplay between ZEB1-AS1 and miR-101/ZEB1 axis contributed to the proliferation and migration of CRC cells, and targeting this interplay could be a promising strategy for CRC treatment.

Quorum-sensing molecules N-acyl homoserine lactones inhibit Trueperella pyogenes infection in mouse model.

Trueperella pyogenes is a gram-positive opportunistic pathogen normally causes mastitis, liver abscesses and pneumonia of economically important livestock. It has been suggested that gram-negative bacteria can suppress the growth and virulence of T. pyogenes in vitro by using the quorum-sensing (QS) signal molecules and cause the transition of predominant species. However, whether these QS signals can be used as potential anti-virulence drugs against T. pyogenes infection is unclear. In this study, the in vivo inhibitory effect N-acyl homoserine lactones (AHLs) from Escherichia coli and Pseudomonas aeruginosa on T. pyogenes was tested by using mouse model. Mice were first peritoneally infected with T. pyogenes followed by intravenous injection of N-Octanoyl-DL-homoserine lactone (C8HSL) or N-(3-oxododecanoyl) homoserine-l-lactone (C12HSL). The results showed that C8HSL and C12HSL significantly reduced bacterial load and increased the survival rate of mice against T. pyogenes challenge. Additionally, the treatment of AHLs promoted the secretion of IL-1ß, IL-6, IL-8 and TNF-α in mouse peritoneal fluid, and significantly decreased the expression levels of virulence genes of residual T. pyogenes. Importantly, murine macrophages rapidly phagocytosed bacteria when they were treated with AHLs compared to untreated cells. Collectively, our findings provide a major advance in understanding the inhibitory effect of AHLs in vivo and a promise for developing new clinical or veterinary treatments of T. pyogenes-related infection.

Stomatin-like protein 2 is overexpressed in cervical cancer and involved in tumor cell apoptosis.

Stomatin-like protein 2 (SLP-2) is overexpressed in numerous types of human cancer and previous studies revealed that SLP-2 may function in mitochondria. The purpose of the present study was to evaluate the expression of SLP-2 in cervical cancer and the association between SLP-2 expression and clinical features, in addition to investigating the role of SLP-2 in the apoptosis of cervical cancer cells. The expression profile of SLP-2 was determined by quantitative polymerase chain reaction, western blotting and immunohistochemical staining. The effect of SLP-2 on cell apoptosis induced by chemotherapeutics in cervical cancer cells was evaluated using Annexin V staining and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assays. The results indicated that SLP-2 expression in cervical cancer was significantly upregulated at the mRNA and protein levels, compared with that in normal cervical tissues. Immunohistochemical analysis revealed significant correlation between SLP-2 protein expression and clinical characteristics, including the squamous cell carcinoma antigen (P=0.003), deep stromal invasion (P=0.021), lymphovascular space involvement (P=0.044) and pelvic lymph node metastasis (P<0.001), which served as independent prognostic factors for predicting the shortening of overall survival time in patients with early-stage cervical cancer. In addition, TUNEL and Annexin V binding assays revealed that silencing SLP-2 expression significantly enhanced the sensitivity of cervical cancer cells to apoptosis induced by chemotherapeutics. Taken together, the results of the present study suggest that SLP-2 may be a progressive gene in the development of cervical cancer. Overexpression of SLP-2 serves an important role in the apoptosis of human cervical cancer cells.

Clinical and biological effects of tumor-associated lymphocytes in the presence or absence of chemotherapy for malignant ascites in ovarian cancer patients.

Tumor-associated lymphocytes (TALs) have been successfully isolated from ascites and solid tumors, however the clinical use of TALs in treating ovarian cancer (OC) has not yet been reported. The present study investigated the efficacy and toxicity of TALs in the presence or absence of chemotherapy in OC patients with malignant ascites (MA). A total of 32 patients were enrolled in this study. A total of 8 patients received treatment with TALs alone (TALs group), 11 patients received combined treatment of TALs and chemotherapy (combination group) and 13 patients received chemotherapy alone (chemotherapy group). The endpoints included Karnofsky performance status (KPS), ascites-associated symptoms (AAS), time to progression (TTP) and overall survival (OS). Compared with the TALs and chemotherapy group, the KPS and AAS in the combination group significantly improved following treatment. Patients in the TALs group (37.5%) and chemotherapy group (53.8%) achieved significantly fewer objective response rates of ascites compared with those in the combination group (90.9%). Furthermore, combination therapy significantly extended TTP (13 months) compared with TALs alone (1 month, P<0.001), and chemotherapy alone (6 months, P=0.027). Similar results were observed for OS between the combination group and the TALs group (25 vs. 7 months, P<0.001). The present study therefore demonstrates that combined therapy of TALs and chemotherapy is safe, feasible, and more effective than chemotherapy or TALs alone in controlling MA and improving the quality of life for OC patients.

[Overexpression of STOML-2 inhibits apoptosis of human cervical squamous carcinoma Siha cells in vitro].

OBJECTIVE: To investigate the mechanism underlying the inhibitory effect of STOML-2 overexpression on apoptosis of human cervical squamous carcinoma Siha cells. METHODS: Siha cells were transfected with an adenoviral vector carrying STOML-2, and 72 h later STOML-2 expression and the proliferation of the cells were detected by Western blotting and MTT assay. The transfected cells were treated with IC50 Cisplatin for 24 h, and the morphological changes of cells were observed using fluorescence, and the cell apoptosis was analyzed using flow cytomerty; the expression levels of proteins related with mitochondrial apoptosis pathway, including caspase-3, cleaved caspase-3, Bcl-2, Bax and cytochrome C (Cyt C), were detected by Western blotting. RESULTS: Western blotting showed a significantly increased STOML-2 expression in the transfected cells. Overexpression of STOML-2 obviously promoted the proliferation of Siha cells. The STOML-2-overexpressing cells exhibited an obvious resistance to IC50 Cisplatin-induced apoptosis as shown by both fluorescence microscopy and flow cytometry and presented with decreased expressions of cleaved caspase-3, Bax, and cytosol Cyt C and increased expressions of caspase-3, Bcl-2, and mitochondrial Cyt C. CONCLUSIONS: Overexpression of STOML-2 can enhance the proliferation of Siha cells by inhibiting cell apoptosis possibly through the mitochondrial apoptosis pathway.

Prognostic significance of pretreatment plasma fibrinogen and platelet levels in patients with early-stage cervical cancer.

BACKGROUND: Hyperfibrinogenaemia and thrombocytosis, which usually occur in cancer patients, have been shown to contribute to cancer cell growth, progression, and metastasis. The aims of the present study were to assess the prognostic significance of pretreatment plasma fibrinogen and platelet levels in early-stage cervical cancer patients. METHODS: The present study was a retrospective analysis of 220 cervical cancer patients with stage I-IIA disease. The pretreatment plasma fibrinogen and platelet levels were investigated along with clinicopathological findings and survival data. RESULTS: The incidences of hyperfibrinogenaemia and thrombocytosis were 11.8 and 25.5%, respectively. Elevated fibrinogen levels were associated with advanced tumour stage, older age, large tumour size, deep stromal invasion, and tumour recurrence, whereas higher platelet levels correlated significantly with advanced tumour stage, large tumour size, and tumour recurrence. Kaplan-Meier analysis showed that hyperfibrinogenaemia and thrombocytosis were significantly associated with shorter disease-free and overall survival. Furthermore, patients with hyperfibrinogenaemia and thrombocytosis may suffer from a higher risk of recurrence. Multivariate survival analyses showed that fibrinogen levels, but not platelet levels, were an independent prognostic factor for poor survival in early-stage patients. CONCLUSION: Hyperfibrinogenaemia and thrombocytosis may be valuable biomarkers for predicting recurrence in patients with early-stage cervical cancer.