Prognostic Indicator For Disease-free Survival Research Articles

Prognostic factors and prognostic model of non-metastatic clear cell renal cell carcinoma

IntroductionAlthough there are some established prognostic evaluation models for clear cell renal cell carcinoma (ccRCC), more robust postoperative prognostic evaluation model is urgently needed. Our study intends to explore new clinical and pathological prognostic factors related to non-metastatic ccRCC, which help to establish a better prognostic risk evaluation model in non-metastatic ccRCC.Patients and methodsA retrospective cohort study was conducted in non-metastatic ccRCC patients spanning from 2010 to 2018. Clinical and pathological factors of these patients were collected. Cox regression analysis was employed to assess the relationship between these factors and disease-free survival (DFS), and a nomogram risk prediction model was also constructed.ResultsA total of 1467 patients were ultimately included, comprising 994 men (67.8%), with 800 patients aged between 40 and 60 years old (54.5%), and 80 patients (5.5%) experiencing relapse or metastasis of ccRCC within three years after operation. The follow-up duration ranged from 39 to 146 months. Univariate and multivariate Cox regression analysis identified five independent prognostic factors of DFS (P < 0.05) including sex, tumor maximum diameter, T stage, lactate dehydrogenase (LDH), and basophils. Leveraging these five factors, we established a prognostic evaluation model demonstrating good predictive efficacy.ConclusionMale, tumor maximum diameter, T stage, LDH, and basophils serve as prognostic indicators for DFS in patients with non-metastatic ccRCC. Patients with high scores based on our model exhibit an elevated likelihood of recurrence or metastasis, thereby potentially selecting postoperative patients with high risk for adjuvant therapy.

Evaluation of forkhead-box C1 expression in breast cancer

Background Forkhead box C1 (FOXC1) is considered an important member of forkhead-box transcription factors. Previous studies have shown that FOXC1 is associated with tumor progression and represents a poor prognostic indicator in triple-negative basal-like breast cancer. Method This is a retrospective study conducted on 187 cases of invasive breast carcinoma obtained from Histopathology Laboratory in Oncology Center, Faculty of Medicine, Mansoura University, starting from 2012. Aim and objectives In this study, we aimed to study FOXC1 protein expression in molecular subtypes of breast cancer and to correlate its expression with other prognostic parameters using immunohistochemistry and tissue microarrays. Results FOXC1-positive expression was seen in 26.7% of cases. Positive FOXC1 expression was most common in triple-negative basal-like breast cancer and HER2-enriched subtypes. Positive FOXC1 expression was higher in ER-negative cases than ER-positive cases (39 vs. 21%) with statistical significance (P = 0.01). Similarly, positive FOXC1 was higher in PR-negative cases than PR-positive cases (37.5 vs. 20%), this was statistically significant (P = 0.009). In our series, FOXC1 expression was not associated with survival. Conclusion FOXC1 expression is associated with negative hormonal-receptor status in breast cancer. FOCX1 is not a prognostic indicator of disease-free survival in our patient series.

The prognostic value of combined tumor markers and systemic immune-inflammation index in colorectal cancer patients.

This study evaluated the significance of combining tumor markers (TM) and systemic immune-inflammation index (SII) for postoperative complications and long-term outcomes in colorectal cancer (CRC) patients. CRC patients (662) who underwent surgery between 2012 and 2014 were retrospectively enrolled into our study. Factors affecting postoperative complications were evaluated by logistic regression analysis. Prognostic factors were assessed using Kaplan-Meier and Cox proportional hazards models. Nomograms were constructed to predict the risk of postoperative complications and survival. A consistency index and a calibration curve were used to evaluate the predictive accuracy of nomograms. TM-SII score was established by combining TM and SII. Logistic regression analyses showed that TM-SII score was an important predictor of postoperative complications in CRC patients. Kaplan-Meier analyses showed that TM-SII score was favorable for prognostic risk stratification. In addition, multivariate analyses indicated that TM-SII score was an independent prognostic indicator for disease-free survival and overall survival. TM-SII based nomograms had a moderate prediction accuracy. TM-SII score is a good prognostic indicator for CRC patients. It may be used as a useful risk stratification tool for advanced CRC patients. TM-SII-based nomograms could be used to identify CRC patients with poor outcomes.

PD-L1 in Lung Adenocarcinoma: Insights into the Role of 18F-FDG PET/CT.

PurposeThis study aimed to evaluate the role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in expression of tumor programmed death ligand-1 (PD-L1) expression and prognostic significance of 18F-FDG PET/CT at different PD-L1 status in patients with lung adenocarcinoma.Patients and MethodsSeventy-three patients with primary lung adenocarcinoma who received 18F-FDG PET/CT before treatment were retrospectively included in this study. Expression of tumor PD-L1, programmed death-1 (PD-1) and glucose metabolic parameters were evaluated.ResultsTumor PD-L1 expression was positively correlated with maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), hexokinase II (HK-II) and glucose transporter 1 (GLUT-1) (P<0.0001 for all). SUVmax was a unique independent predictor of tumor PD-L1 expression, with an optimal cut-off value of 9.5. For all the patients, tumor stage (P<0.001) and SUVmax (P=0.009) were independent prognostic indicators of disease-free survival (DFS)/progression-free survival (PFS) while carcino-embryonic antigen (CEA) (P=0.003), Ki67 (P=0.042), PD-L1 (P=0.048) and TLG (P=0.004) were independent prognostic indicators of overall survival (OS). Tumor stage (P=0.004) and SUVmax (P=0.022) were independent prognostic indicators of DFS/PFS while TLG (P=0.012) and CEA (P=0.045) were independent prognostic indicators of OS in the PD-L1-positive group. In the PD-L1-negative group, tumor stage (P=0.002) and CEA (P=0.006) were unique independent prognostic indicators of DFS/PFS and OS, respectively.Conclusion18F-FDG PET/CT may potentially predict tumor PD-L1 expression and play a role in predicting prognosis of PD-L1/PD-1 immunotherapy in lung adenocarcinoma.

Clinicopathological Relevance and Prognostic Value of Androgen Receptor in Mammary Paget’s Disease with Underlying Invasive Ductal Carcinoma

Introduction: Mammary Paget’s disease (MPD) is a rare cutaneous manifestation. Epidemiologically, more than half of the MPD patients concurrently have underlying invasive ductal carcinoma (MPD-IDC), and their prognosis remains poor despite multimodal treatments of breast cancer have markedly improved patients’ survival. Accordingly, it is crucial to seek out novel therapeutic targets of MPD-IDC. As an emerging biological marker, the value of androgen receptor (AR) in MPD-IDC is inconsistent. Our objectives were to investigate the associations between AR and clinicopathological factors, and to explore its prognostic value in MPD-IDC. Methods: We retrospectively analyzed data from 103 MPD-IDC patients, and immunohistochemical staining was used to determine their AR statuses. Results: AR was expressed in 44 patients (42.7%), and AR expression was significantly correlated with body mass index (BMI) (p = 0.038) and axillary lymph node (ALN) status (p = 0.025). Kaplan-Meier curves showed that AR positivity was significantly associated with better overall survival (OS) in MPD-IDC patients (p = 0.019) and estrogen receptor-negative MPD-IDC patients (p = 0.039). Multivariate Cox regression analysis revealed that AR was not an independent prognostic indicator of disease-free survival (DFS) or OS in MPD-IDC patients (p = 0.395 and p = 0.073, respectively). Conclusions: In contrast to AR-negative tumors, patients with AR-positive ones were more likely to have lower BMI, no ALN metastasis, and better OS. AR-targeted treatments for MPD-IDC may add to existing therapeutic approaches to improve their effectiveness.

Long non-coding RNA ZFAS1 promotes the expression of EPAS1 in gastric cardia adenocarcinoma

IntroductionLncRNA (Long non-coding RNA) ZFAS1 (zinc finger antisense 1) functions as the oncogene in multiple cancers, including gastric cancer. However, its function and underlying mechanism in the GCA (gastric cardia adenocarcinoma), the most aggressive type of gastric cancer, remain unknown. ObjectiveIn the current study, the expression level of LncRNA ZFAS1 was quantified in 762 GCA tissues and the paired adjacent non-tumor tissues. The expression level of LncRNA ZFAS1 was quantified in 762 GCA tissues and the paired adjacent non-tumor tissues, and further confirmed using in vitro cell and animal model based assays. ConclusionWe demonstrated here that the LncRNA ZFAS1 was up-regulated in GCA tissues. Furthermore, the elevated level of ZFAS1 was significantly associated with the GCA metastasis and cancer recurrence. It was also demonstrated to be an independent prognostic indicator of disease-free survival and overall survival for GCA patients. RNA sequencing showed that the up-regulated ZFAS1 was tightly associated with the down-regulated hypoxia inducible factor 1 (HIF1) and up-regulated EPAS1 (Endothelial PAS domain protein 1, also known as HIF2). In vitro studies showed that the ZFAS1 could bind to EPAS1, enhance its abilities to epigenetically silence the HIF1, and promote its own expression in GCA cell lines. In the animal model, codelivering the EPAS1 and the ZFAS1 antisense oligos could significantly boost up their therapeutic effects on tumor growth. Thus, targeting ZFAS1 and EPAS1 might be an alternative therapeutic option in GCA.

A 10-year review of primary major salivary gland cancers.

Primary salivary gland cancers comprise a heterogeneous group of histological entities and represent less than 5% of head and neck malignancies. Surgical resection is the main treatment, and adjuvant radiotherapy is performed in selected cases. Chemotherapy is an option in metastatic or recurrent disease, with poor evidence. We aimed to review a 10-year experience of a cancer centre on major salivary gland cancers, focusing on clinical, pathological, treatment and patients’ outcomes data.A total of 93 patients were identified, median age at diagnosis was 64 years (IQR, 23), and 51.6% were male. The parotid gland was the site of origin in 76.3% of cases. The most frequent histological type was salivary duct carcinoma (21.5%). All patients were submitted to surgery and adjuvant radiotherapy was performed in 74.2%. From 26 patients diagnosed with metastatic disease, 9 were treated with systemic therapy. At 8 years, disease-free survival was 54.6% and overall survival was 48.4%. Male sex, salivary duct carcinoma, stage pT3-4, stage pN2-3, high histologic grade, lymphovascular invasion and perineural invasion were negative prognostic indicators for disease-free survival and overall survival. Extracapsular spread was a negative prognostic indicator for overall survival. In the multivariable analysis, histological type—salivary duct carcinoma—kept significant negative impact in disease-free survival and high histologic grade in overall survival.The most frequent histological type was salivary duct carcinoma, which is estimated to represent only 9% of salivary tumours. Patients with salivary duct carcinoma relapsed more than other histological types. High histologic grade was a negative prognostic indicator for overall survival.

Prognostic value of systemic inflammatory marker in patients with head and neck squamous cell carcinoma undergoing surgical resection.

Aim: To explore the prognostic value of the systemic inflammatory marker (SIM) based on neutrophil, lymphocyte and monocyte counts in head and neck squamous cell carcinoma (HNSCC) patients. Patients & methods: We retrospectively collected the data of 367 patients with HNSCC who underwent surgery. The Kaplan-Meier survival analysis and Cox regression analysis were conducted on disease-free survival and overall survival. Results: A high SIM (>1.34) was associated with larger tumor size, advanced clinical stage and shorter survival time. The survival analysis showed that only clinical stage and SIM were independent prognostic indicators of disease-free survival and overall survival. Conclusion: The SIM positively correlated with tumor progression and might be a powerful prognostic indicator of poor outcome in patients with HNSCC.

Correlation analysis of preoperative magnetic resonance cholangiopancreatography and prognosis in hilar cholangiocarcinoma

To determine the presence and extent of preoperative biliary obstructions, using magnetic resonance cholangiopancreatography (MRCP), and to determine the clinicopathological consequences of these obstructions in a group of 83 patients with hilar cholangiocarcinoma (HC). Fifty-five HC patients with biliary obstruction and 28 HC patients without biliary obstruction were included in the study. The associations between biliary obstruction (assessed using MRCP) and clinicopathological characteristics were analysed. Patients with biliary obstruction had a higher liver function and serum carbohydrate antigen than those without biliary obstruction. The Bismuth-Corlette classification, tumour stage and lymph node metastasis were identified as independent relative factors of biliary obstruction, while differentiation and biliary obstruction were identified as independent factors of overall survival. Furthermore, the size of the tumour, differentiation and biliary obstruction were independent prognostic indicators of disease-free survival for HC patients. The presence and extent of preoperative biliary obstruction, measured by MRCP, was associated with aggressive clinicopathological features and indicated poor prognosis in HC patients.

Identification and Validation of Tumor Stromal Immunotype in Patients With Hepatocellular Carcinoma.

Background: The immune landscape of hepatocellular carcinoma (HCC) is heterogeneous. This study aims to develop the immune type which could improve predictive value of HCC survival.Methods: A total of 208 HCC patients in the testing cohort, 112 patients in the validation cohort and 365 HCC patients in the TCGA database were included in this study. Immune features were assessed by immunohistochemical staining or CIBERSORT method. We constructed prognostic classifiers by LASSO COX analyses in the TCGA cohort, which identified five features out of the 22 types of immune cells.Results: The formulas based on the immunohistochemical staining are as follows: ISOS = 0.648* Macrophagestromal + 0.444*Neutrophilsstromal + 0.218*Tregsstromal – 0.703*Memory T cellsstromal; ISDFS = 0.285*B cellsstromal + 0.494*Neutrophilsstromal + 0.431*Tregsstromal – 0.736*Memory T cellsstromal. We classified HCC patients into immune type A subgroup (IS-A) and type B subgroup (IS-B) based on immune scores. The immune type was an independent prognostic indicator for disease-free survival (DFS) and overall survival (OS) in both testing and validation cohorts. Two nomograms (for OS and DFS) that integrated the immune type and clinicopathologic risk factors also showed good predictive accuracy and discriminatory power. IS-A group was correlated with higher immune checkpoint molecule expression. In addition, patients with IS-A and IS-B had distinct mutation signature.Conclusion: The immune types could predict survival and recurrence of HCC effectively. In addition, the immunosuppressive pathways and mutation signature are distinct between two immune types.

Development and Validation of Tumor Stromal Immunotype in Patients with Hepatocellular Carcinoma

Background: The immune landscape of hepatocellular carcinoma (HCC) is heterogeneous. This study aims to develop the immune type which could improve predictive value of HCC survival. Methods: A total of 208 HCC patients in the testing cohort, 112 patients in the validation cohort and 365 HCC patients in the TCGA database were included in this study. Immune features were assessed by immunohistochemical staining or CIBERSORT method. We constructed prognostic classifiers by LASSO COX analyses in the TCGA cohort, which identified five features out of the 22 types of immune cells. Results: The formulas based on the immunohistochemical staining are as follows: ISOS= 0.648* Macrophagestromal + 0.444*Neutrophilsstromal + 0.218*Tregsstromal - 0.703*Memory T cellsstromal; ISDFS = 0.285*B cellsstromal + 0.494*Neutrophilsstromal + 0.431*Tregsstromal - 0.736*Memory T cellsstromal. We classified HCC patients into immune type A subgroup (IS-A) and type B subgroup (IS-B) based on immune scores. The immune type was an independent prognostic indicator for disease-free survival (DFS) and overall survival (OS) in both testing and validation cohorts. Two nomograms (for OS and DFS) that integrated the immune type and clinicopathologic risk factors also showed good predictive accuracy and discriminatory power. IS-A group was correlated with higher immune checkpoint molecule expression. In addition, patients with IS-A and IS-B had distinct mutation signature. Conclusion: The immune types could predict survival and recurrence of HCC effectively. In addition, the immunosuppressive pathways and mutation signature are distinct between two immune types. Funding Statement: This work was supported by grants from the Science and Technology Support Program of Sichuan Province (2017SZ0003) and the Natural Science Foundation of China (81770615, 81700555, 81672882 and 81502441). Declaration of Interests: The authors declare: None. Ethics Approval Statement: The present study was performed after approval by the ethic committee of the West China Hospital, Sichuan University.

Prognostic value of advanced lung cancer inflammation index in head and neck squamous cell carcinoma

The advanced lung cancer inflammation index (ALI) is a useful tool for prediction of outcome in several malignancies. However, to date, its significance in head and neck cancer patients has not been evaluated. We retrospectively analyzed data from 93 patients who were diagnosed with head and neck squamous cell carcinoma (HNSCC) and treated with surgical resection and postoperative radiotherapy between 2002 and 2012. The aim of this study was to investigate whether the preoperative ALI is a prognostic indicator for disease-free survival and overall survival in HNSCC patients. A low ALI was significantly associated with a worse 5-year disease-free survival (47.0 vs. 83.5%, p < 0.001), and overall survival (44.4 vs. 73.6%, p = 0.008). Multivariate analysis showed that low ALI was independently associated with disease-free survival (p < 0.001) and overall survival (p = 0.02). The ALI could serve as an easily available prognostic indicator for disease-free and overall survival prediction in patients with HNSCC.

NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma.

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.

Reduced interleukin-38 in non-small cell lung cancer is associated with tumour progression.

Lung cancer continues to be the leading cause of cancer-related deaths worldwide due to its high incidence, malignant behaviour and lack of major advancements in treatment strategy. The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-38 (interleukin-38), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. We first evaluated the IL-38 expression in 384 pairs of NSCLC samples and their adjacent normal mucosa by real-time PCR, ELISA (enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-38 on patient survival rates, cancer progression and their sensitivity to chemotherapy drugs was assessed. IL-38 was barely expressed in the NSCLC tissues but highly expressed in the adjacent normal tissues. The downregulation of IL-38 was significantly correlated with the results of the American Joint Committee on Cancer stage and degree of differentiation, and it was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with NSCLC. Overexpression of IL-38 in NSCLC cells suppressed cell migration, invasion, proliferation and colony formation through suppressing β-catenin. IL-38 inhibited NSCLC formation in a mice model and sensitized the cancer cells to chemotherapy drugs. Our results show that IL-38 plays an inhibitory role in NSCLC development and functions as a novel prognostic indicator and a potential therapeutic target.

Impact of re-excision of residual adjacent vulvar intraepithelial neoplasia (VIN III) and histological tumour-free margin (hTFM) on survival in primary squamous cell carcinoma of vulva.

hTFM in primary vulvar cancer is an important prognostic factor. Ideally, a diameter of > 8mm should be achieved after primary surgery. The role of VIN III persistence after primary surgery in vulvar cancer is still unclear. The main objective of the current study was to study the role of residual VIN III re-excision and compare differences in disease-free survival among patients with different hTFM and in primary vulvar cancer. Forty-two patients with residual adjacent VIN III after primary surgery for vulvar cancer which were operated between 2000 and 2016 in our clinic were enrolled in this retrospective study. Re-excision rates for residual adjacent VIN III were calculated. According to the histological margin patients were divided into three group: < 3, 3-8 and > 8mm. Univariate and multivariate analyses were conducted using the Kaplan-Meier method and Cox proportional hazards models, respectively. The vast majority of patients had pT1b stage (57.1%), grading G2 (71.4%) and lymph node-negative (45.3%) disease at first diagnosis. The re-excision rate was 57.1%. The 5-year disease-free survival (DFS) rates in patients with < 3, 3-8 and > 8mm hTFM were 50.0, 50.0 and 81.0%, respectively (p = 0.032). The 5-year DFS rates in patients with re-excision and without re-excision for VIN III were 77.3 and 52.9%, respectively (p = 0.060). In univariate analysis was solely hTFM > 8mm a prognostic factor for DFS (p = 0.017). hTFM may be a potential prognostic indicator for DFS in vulvar cancer patients. Re-excision for residual adjacent VIN III could not be established as a prognostic factor for DFS after primary surgery in squamous cell cancer of vulva.

Sperm-Associated Antigen 5 Expression Is Increased in Hepatocellular Carcinoma and Indicates Poor Prognosis

BackgroundSperm-associated antigen 5 (SPAG5), a gene that encodes a mitotic spindle-associated protein, is closely related to tumor development and is involved in cell migration and proliferation. The objective of this research was to explore the clinical significance of SPAG5 expression in hepatocellular carcinoma (HCC) and the relationship between SPAG5 expression and HCC prognosis.Material/MethodsTwenty pairs of fresh-frozen HCC samples and samples from 95 HCC patients in a tissue microarray were subjected to quantitative real-time reverse-transcription (qRT)-PCR and immunohistochemistry (IHC), respectively, to investigate the relationship between the expression of SPAG5 and the clinicopathological features of HCC patients.ResultsPCR data showed that the messenger RNA (mRNA) expression level of SPAG5 in HCC tissue specimens was higher than that in adjacent non-tumor tissue specimens (p<0.05). IHC analyses demonstrated that SPAG5 expression was significantly correlated with tumor grade (p=0.003), tumor number (p=0.009), vascular invasion (p=0.001), and TNM stage (p=0.001). Survival analysis and Kaplan-Meier curves showed that SPAG5 expression is an independent prognostic indicator for disease-free survival (p=0.017) and overall survival (p=0.016) in HCC patients.ConclusionsOur results indicate that SPAG5 expression may be considered as an oncogenic biomarker and a novel predictor for HCC prognosis.

PODXL, negatively regulated by KLF4, promotes the EMT and metastasis and serves as a novel prognostic indicator of gastric cancer

BackgroundPodocalyxin-like 1 (PODXL) was reported to be closely associated with the development of various cancers, yet its functional roles and molecular mechanisms remain vague. The aim of our study was to investigate the clinical significance, biological function and molecular mechanism of PODXL in gastric cancer (GC).MethodsThe level of PODXL in GC tissues was detected applying GC tissues microarray, fresh GC tissues and public database (Oncomine). The invasion, metastasis and tumorigenesis role of PODXL were performed in vitro and in vivo. The correlations between KLF4 and PODXL was determined in GC tissues microarray and fresh GC tissues, and the molecular regulatory mechanism between KLF4 and PODXL was explored in vitro.ResultsThe high level of PODXL was detected in GC tissues with advanced T stage, lymph node metastasis, Union for International Cancer Control stage and poor differentiation. And Cox proportional hazards model revealed that PODXL can serve as an independent prognostic indicator for disease-free survival and overall survival of GC patients. Moreover, downregulation of PODXL could inhibit EMT and reduce invasion and metastasis in vitro as well as tumorigenesis in vivo. Additionally, our findings showed that PODXL may be a significant downstream target of KLF4.ConclusionsKLF4/PODXL signaling pathway assumes an irreplaceable role in tumorigenesis, invasion and metastasis of human GC and PODXL serves as an independent prognostic indicator for GC patients.

Carbohydrate Antigen 19-9 Increases the Predictive Efficiency of a-Fetoprotein for Prognosis of Resected Hepatocellular Carcinoma

Serum α-fetoprotein (AFP) is a classical biomarker for both diagnosis and prognosis of hepatocellular carcinoma (HCC). However, its predictive efficiency for prognosis remains unsatisfactory. This study explores whether integrating AFP and carbohydrate antigen (CA) 19-9/carcinoembryonic antigen (CEA) increase its prognostic efficiency in HCC. A total of 67 HCC patients with complete record of AFP, CA19-9, and CEA, who underwent radical hepatectomy, were included. The sole and combined evaluations for prognostic significance of the three markers were performed. In the first, it was found by one-factor analysis that AFP was a univariate prognostic indicator for disease-free survival, but not overall survival, whereas CEA and CA19-9 were not statistically significant, although the latter was of marginally predictive significance for disease-free survival. Subsequently, it was revealed that combined evaluation of AFP and CA19-9, rather than AFP and CEA, distinguished overall and disease-free survival more effectively, compared with single ones. However, this combination was not significant in multivariate Cox regression analysis, thus needing further validation, especially in large-scale prospective investigations. The addition of vascular invasion to AFP/CA19-9 combination might provide enhanced predictive power for disease-free survival. Collectively, these results preliminarily suggest that CA19-9 increases the predictive efficiency of AFP for prognosis of HCC after resection.

Prognostic significance of combined fibrinogen concentration and neutrophil-to-lymphocyte ratio in patients with resectable non-small cell lung cancer.

Objective:Cancer-associated inflammation and coagulation cascades play vital roles in cancer progression and survival. In this study, we investigated the significance of the combination of preoperative fibrinogen and the neutrophil-to-lymphocyte ratio (NLR) in predicting the survival of patients with non-small cell lung cancer (NSCLC).Methods:We retrospectively enrolled 589 patients with NSCLC who underwent surgery. The univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators, including the combination of fibrinogen and NLR (F-NLR). The cut-off values for fibrinogen, NLR, and clinical laboratory variables were defined by the receiver operating characteristic (ROC) curve analysis. According to the ROC curve, the recommended cut-off values for fibrinogen and the NLR were 3.48 g/L and 2.30, respectively. Patients with both a high NLR (≥ 2.30) and hyperfibrinogenemia (≥ 3.48 g/L) were given a score of 2, whereas those with one or neither were scored as 1 or 0, respectively.Results:Our results showed that F-NLR was an independent prognostic indicator for disease-free survival (DFS) [hazard ratio (HR), 1.466; 95% confidence interval (CI), 1.243–1.730; P < 0.001] and overall survival (OS) (HR, 1.512; 95% CI, 1.283–1.783; P < 0.001). The five-year OS rates were 66.1%, 53.5%, and 33.3% for the F-NLR = 0, F-NLR = 1, and F-NLR = 2, respectively ( P < 0.001). Correspondingly, their five-year DFS rates were 62.2%, 50.3%, and 30.4%, respectively ( P < 0.001). In the subgroup analyses of the pathological stages, the F-NLR level was significantly correlated with DFS and OS in stage I and IIIA cancers. Conclusions:Preoperative F-NLR score can be used as a valuable prognostic marker for patients with resectable early-stage NSCLC.

Interleukin-35 Expression in Non-Small Cell Lung Cancer is Associated with Tumor Progression

Lung cancer continues to be the leading cause of cancer related deaths worldwide due to its high incidence, malignant behavior and lack of major advancements in treatment strategy. The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-35 (Interleukin 35), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. We first evaluated the IL-35 expression in 384 pairs of NSCLC samples and their adjacent normal mucosa by realtime PCR, ELISA (Enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-35 on patient survival rates, cancer progression and their sensitivity to chemotherapy drugs were assessed. IL-35 was barely expressed in the NSCLC tissues but highly expressed in the adjacent normal tissues. The down-regulation of IL-35 was significantly correlated with the results of American Joint Committee on Cancer stage, differentiation and it was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with NSCLC. Overexpression of IL-35 in NSCLC cells suppressed cell migration, invasion, proliferation, colony formation through suppressing β-catenin. IL-35 inhibited NSCLC formation in the mice model and sensitize the cancer cells to chemotherapy drugs. Our results showed that IL-35 plays an inhibitory role in NSCLC development and function as a novel prognostic indicator and a potential therapeutic target.