Pingping Hu

Tumor-Associated Neutrophils as a New Prognostic Factor in Cancer: A Systematic Review and Meta-Analysis

Purpose Tumor-associated neutrophils (TAN) have been reported in a variety of malignancies. We conducted an up-to-date meta-analysis to evaluate the prognostic role of TAN in cancer. Method Pubmed, Embase and web of science databases were searched for studies published up to April 2013. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. The impact of neutrophils localization and primary antibody were also assessed. Results A total of 3946 patients with various solid tumors from 20 studies were included. High density of intratumoral neutrophils were independently associated with unfavorable survival; the pooled HRs were 1.68 (95%CI: 1.36–2.07, I2 = 55.8%, p<0.001) for recurrence-free survival (RFS)/disease-free survival (DFS), 3.36 (95%CI: 2.08–5.42, I2 = 0%, p<0.001) for cancer-specific survival (CSS) and 1.66 (95%CI: 1.37–2.01, I2 = 70.5%, p<0.001) for overall survival (OS). Peritumoral and stromal neutrophils were not statistically significantly associated with survival. When grouped by primary antibody, the pooled HRs were 1.80 (95%CI: 1.47–2.22, I2 = 67.7%, p<0.001) for CD66b, and 1.44 (95%CI: 0.90–2.30, I2 = 45.9%, p = 0.125) for CD15, suggesting that CD66b positive TAN might have a better prognostic value than CD15. Conclusion High levels of intratumoral neutrophils are associated with unfavorable recurrence-free, cancer-specific and overall survival.

Prognostic Significance of Systemic Inflammation-Based Lymphocyte- Monocyte Ratio in Patients with Lung Cancer: Based on a Large Cohort Study

Increasing evidence indicates cancer-related inflammatory biomarkers show great promise for predicting the outcome of cancer patients. The lymphocyte- monocyte ratio (LMR) was demonstrated to be independent prognostic factor mainly in hematologic tumor. The aim of the present study was to investigate the prognostic value of LMR in operable lung cancer. We retrospectively enrolled a large cohort of patients with primary lung cancer who underwent complete resection at our institution from 2006 to 2011. Inflammatory biomarkers including lymphocyte count and monocyte count were collected from routinely performed preoperative blood tests and the LMR was calculated. Survival analyses were calculated for overall survival (OS) and disease-free survival (DFS). A total of 1453 patients were enrolled in the study. The LMR was significantly associated with OS and DFS in multivariate analyses of the whole cohort (HR = 1.522, 95% CI: 1.275–1.816 for OS, and HR = 1.338, 95% CI: 1.152–1.556 for DFS). Univariate subgroup analyses disclosed that the prognostic value was limited to patients with non-small-cell lung cancer (NSCLC) (HR: 1.824, 95% CI: 1.520–2.190), in contrast to patients with small cell lung cancer (HR: 1.718, 95% CI: 0.946–3.122). Multivariate analyses demonstrated that LMR was still an independent prognostic factor in NSCLC. LMR can be considered as a useful independent prognostic marker in patients with NSCLC after complete resection. This will provide a reliable and convenient biomarker to stratify high risk of death in patients with operable NSCLC.

Prognostic role of Twist or Snail in various carcinomas: a systematic review and meta-analysis

Twist and Snail are considered as key transcriptional repressors of E‐cadherin tightly related to epithelial‐to‐mesenchymal transition (EMT) and cancer progression. Numerous studies have investigated the prognostic value of Twist and Snail. However, the published results were controversial or even opposite. Our article aimed to evaluate the prognostic role of Twist and Snail in patients with cancer.

The Number of Resected Lymph Nodes (nLNs) Combined with Tumor Size as a Prognostic Factor in Patients with Pathologic N0 and Nx Non-Small Cell Lung Cancer

Background The prognostic role of the number of resected lymph nodes (nLNs) in pathologic N0 (lymph node negative) and Nx (no lymph node examined) non-small cell lung cancer (NSCLC) patients remains uncertain. Guidelines for optimal nLNs have not been established. In the current study, we evaluated whether a higher number of resected lymph nodes (LNs) results in better survival in different tumor size categories among NSCLC patients without metastatic LNs. Method A retrospective study was conducted. Based on nLNs (LN = 0, 1–7, >7) and tumor size (Ta: ≤3.5cm, Tb: >3.5cm) during surgery, patients were categorized into 6 groups (LN0Ta, LN0Tb, LN1–7Ta, LN1–7Tb, LN7-Ta and LN7-Tb). Survival and multivariate analyses were carried out to determine whether nLNs combined with tumor size was significant for overall survival (OS) or disease free survival (DFS) after adjusting for potential confounders. Results A total of 428 patients were enrolled in the study. Multivariate analysis demonstrated that nLNs, tumor size and pathological stage were the independent prognosticators for OS and DFS. Data from our study suggested that lung cancer lymphadenectomy with more than 7 LNs removed should be considered a benchmark for surgery or pathology at an early stage. Survival was significantly better in the LN7-Ta group, compared with other 5 groups (p<0.001). Conclusions The combined predictor (nLNs combined with tumor size) is an independent prognostic factor and a reasonable stratification criterion in patients with pathologic N0 and Nx NSCLC. The validation of our finding is warranted in further investigation.

Invasion Types Are Associated With Poor Prognosis in Lung Squamous Carcinoma Patients

AbstractAlthough the prognostic significance of the histologic patterns in lung adenocarcinoma is being identified, no significant prognostic indicators in lung squamous carcinoma are accepted as a standard universally. The aim of this study was to evaluate the histologic characteristics incorporating the defined invasion types and distinguish the features that can reflect prognosis.We reviewed all slices of 132 patients with lung squamous carcinoma. The cases were classified according to the World Health Organization (WHO) classification and were evaluated for tumor budding, single cell invasion, large cell invasion, cytologic atypia degree, mitotic count, number of buds, tumor nest size, fibrosis, and necrosis.In univariate analysis, overall survival was associated significantly with age (P = 0.023), lymph nodes metastasis (P < 0.001), distant organ metastasis (P < 0.001), pleural invasion (P < 0.001), tumor budding (P = 0.003), single cell invasion (P = 0.001), mitotic count (P < 0.001), and the cytologic atypia degree (P = 0.009). However, the subtypes of 2004 WHO classification showed no association with outcome (P = 0.209). In multivariate analysis, the independent significant prognostic indicators of lung squamous carcinoma were tumor budding (hazard ratio [HR] = 0.466, P = 0.005), single cell invasion (HR = 0.447, P = 0.003), mitotic count (HR = 0.502, P = 0.048) and cytologic atypia degree (HR = 0.479, P = 0.024).Lung squamous carcinomas with the invasion types were associated with a poor prognosis.

Haemoptysis as a prognostic factor in lung adenocarcinoma after curative resection.

Background:Haemoptysis is a common symptom of lung cancer. Its prognostic role and mechanisms are still poorly understood.Methods:We retrospectively reviewed 666 consecutive patients with primary lung adenocarcinoma who underwent complete resection. The prognostic value of haemoptysis with respect to overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) was analysed. To further explore the possible mechanisms of haemoptysis, we evaluated vascular endothelial growth factor (VEGF) expression, tumour necrosis, vascular invasion and extratumoural microvessel density (MVD) in 112 randomly selected patients.Results:Haemoptysis predicted poor OS, DSS and DFS in operable lung adenocarcinoma (all P<0.001). In addition, haemoptysis was associated with high white blood cell (WBC) count (P=0.032), high fibrinogen (Fib; P<0.001), high tumour greatest dimension (P<0.001), severe vascular invasion (P=0.002) and central tumour location (P<0.001). We obtained no statistically significant differences of VEGF expression, tumour necrosis and extratumoural MVD in haemoptysis and non-haemoptysis groups.Conclusion:Our study demonstrates that haemoptysis predicts poor OS, DSS and DFS in lung adenocarcinoma after curative resection. Vascular invasion rather than angiogenesis or tumour necrosis could be the most important mechanism of haemoptysis in lung adenocarcinoma.

Albumin and Neutrophil Combined Prognostic Grade as a New Prognostic Factor in Non-Small Cell Lung Cancer: Results from a Large Consecutive Cohort

Objectives It has been reported nutritional status and systemic inflammation were associated with the outcome of patients with malignancies. However, the prognostic value of combination of them was really scarce, especially in non-small cell lung cancer (NSCLC). In order to find a more simple and efficient predictor, we hypothesized that pretreatment albumin and neutrophil combined prognostic grade (ANPG) could offer an improved prognostic ability in NSCLC patients. Methods We collected pretreatment albumin and neutrophil, clinicopathological, treatment and follow-up data of 1033 consecutive NSCLC patients treated between 2006 and 2011 in this retrospective study. The ANPG was calculated according to pretreatment albumin and neutrophil levels dichotomized by the optimal cut-off values, the quartile values and the clinical reference values. Kaplan-Meier (K-M) curves and Cox proportional regression were used for survival analyses. All the data was analyzed by SPSS 20.0. Results According to optimal cut-off values and quartile values, significant differences were found in different pretreatment albumin, neutrophil levels and ANPG from the K-M curve (all p<0.05). Univariate analyses and multivariate analyses disclosed ANPG was a more sensitive independent predictor for both overall survival (OS) and progression free survival (PFS) than either albumin level or neutrophil level (HRs were higher for ANPG). As for clinical reference values, no significant difference of pretreatment albumin levels was found in K-M curve and univariate analyses. All three indexes lost their significance in multivariate analyses. Conclusion Higher ANPG predicts worse OS and PFS in NSCLC patients independently, and it is more sensitive than hypoalbuminaemia and neutrophilia. It might be used as a reliable, convenient and more sensitive predictor to assist the identification of patients with poor prognosis and be a hierarchical factor in the future NSCLC clinical trials.

Intratumoral polymorphonuclear granulocyte is associated with poor prognosis in squamous esophageal cancer by promoting epithelial–mesenchymal transition

AIM The role of polymorphonuclear granulocyte (PMN) infiltration in tumor remains unclear in esophageal cancer (EC). MATERIALS & METHODS We conducted a retrospective study on consecutive patients with primary squamous EC. The potential roles of PMN infiltration into tumor nests were assessed by immunohistochemistry. The interactions of PMNs and tumor cells were investigated in an in vitro coculture system. RESULTS Intratumoral PMN is an independent prognostic factor. PMN infiltration induces epithelial-mesenchymal transition of cancer cells with the initiation of TGF-β/Smad signaling pathway. CONCLUSION Our study demonstrates intratumoral PMN is an independent unfavorable predictor in squamous EC. PMN promotes cancer progression partly by its ability to induce epithelial-mesenchymal transition via TGF-β/Smad signaling pathway.

The Synergistic Effect of Humanized Monoclonal Antibodies Targeting Insulin-Like Growth Factor 1 Receptor (IGF-1R) and Chemotherapy

IGF-1R, an important member of the IGF signaling system, is a plasma-membrane-bound receptor composed of two α-subunits and two β-subunits. IGF-1R has been revealed to play a pivotal role in cancer cell proliferation, differentiation, apoptosis and phenotype transformation, resulting uncontrolled tumor-cell growth. During the last decades, IGF-1R monoclonal antibody combined with chemotherapeutic agents as a novel cancer treatment approach has shown synergistic effect in cancer treatment in some preclinical and clinical trials. Prolonged progression-free survival rate, objective response rate and stable disease were shown in some sorts of cancer patients compared to those implemented traditional standard chemotherapy. However, not all related clinical trials demonstrated expected promising outcomes. Most treatment-related adverse events in those studies are mild and manageable. The most frequently happened side effect is hyperglycemia in majorities of combined cancer therapy studies. Herein, we summarized the recent online and published literatures concerning the safety, tolerability, anti-tumor activity and adverse events of this novel strategy. Besides, this work attempts to provide convincible evidence to warrant further investigation to identify prognostic biomarkers on neoplasm.

Predictive value of inflammatory indexes on the chemotherapeutic response in patients with unresectable lung cancer: A retrospective study

Chemotherapy is widely administered to patients with advanced lung cancer; however, data regarding chemotherapeutic sensitivity are limited. The present study aimed to investigate the predictive value of inflammatory indexes for chemotherapeutic efficacy in advanced lung cancer. Patients with stage III and IV unresectable lung cancer that were treated with first-line chemotherapy between January 2007 and December 2011 were retrospectively identified, and chemotherapeutic response was evaluated following 2 or 3 chemotherapy cycles. Prior to chemotherapy, hematologic data and clinicopathological parameters were collected using electronic medical records. The associations between the main inflammatory indexes [which included the pretreatment neutrophil count (PNC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR)] and the chemotherapeutic efficacy, as well as the prognostic value of the indexes, were analyzed. According to the receiver operating characteristic curve, PLR failed to reach diagnostic accuracy for overall chemotherapeutic response. PNC and NLR were each classified into two groups according to the cut-off values (4.635×109/l for PNC and 2.443 ×109/l for NLR). The overall response rate was significantly higher in the low PNC [odds ratio, 3.261; 95% confidence interval (CI), 2.102-5.060; P<0.001, vs. high PNC] and low NLR groups (odds ratio, 1.596; 95% CI, 1.037-2.454; P=0.033, vs. high NLR). Univariate analyses showed that the high PNC (HR, 1.487) and high NLR groups (HR, 1.288) were associated with poor progression-free survival (PFS); however, NLR was considered statistically insignificant in multivariate analysis. In summary, high PNC and NLR values are associated with chemoresistance and an unfavorable prognosis, with the present study demonstrating that PNC has increased sensitivity when compared with other inflammatory indexes in predicting chemotherapeutic efficacy. Therefore, PNC has the potential to be used as a reliable and suitable predictor to stratify a high risk of chemoresistance in patients with stage III and IV unresectable lung cancer.