Prognostic value of preoperative mean corpuscular volume in esophageal squamous cell carcinoma

AIM: To evaluate whether preoperative mean corpuscular volume (MCV) is a prognostic indicator in patients with resectable esophageal squamous cell carcinoma (ESCC). METHODS: A total of 298 consecutive, prospectively enrolled patients with histologically diagnosed ESCC who underwent surgery with curative intent from 2001 to 2011 were retrospectively evaluated. Patients were excluded if they had previous malignant disease, distant metastasis at the time of primary treatment, a history of neoadjuvant treatment, had undergone nonradical resection, or had died of a non-tumor-associated cause. Survival status was verified in September 2011. Pathological staging was performed based on the 2010 American Joint Committee on Cancer criteria. Preoperative MCV was obtained from blood counts performed routinely within 7 d prior to surgery. Receiver operating characteristic (ROC) curve analysis was used to determine a cutoff for preoperative MCV. RESULTS: The 298 patients consisted of 230 males and 68 females, with a median follow-up of 30.1 mo. ROC analysis showed an optimal cutoff for preoperative MCV of 95.6 fl. Fifty-nine patients (19.8%) had high (> 95.6 fl) and 239 (80.2%) had low (≤ 95.6 fl) preoperative MCV. Preoperative MCV was significantly associated with gender (P=0.003), body mass index (P=0.017), and preoperative red blood cell count (P<0.001). The predicted 1-, 3and 5-year overall survival (OS) rates were 72%, 60% and 52%, respectively. Median OS was significantly longer in patients with low than with high preoperative MCV (27.5 mo vs 19.4 mo, P<0.001). Multivariate analysis showed that advanced pT (P=0.018) and pN (P<0.001) stages, upper thoracic location (P=0.010), lower preoperative albumin concentration (P=0.002), and high preoperative MCV (P=0.001) were negative prognostic factors in patients with ESCC. Preoperative MCV also stratified OS in patients with T3, N1-N3, G2-G3 and stage Ⅲ tumors. CONCLUSION: Preoperative MCV is a prognostic factor in patients with ESCC.

Screening study on new tumor marker periplakin for lung cancer

Objective: The aim of this study was to use lung cancer targeting binding polypeptide ZS-9 to screen cDNA library of human lung cancer and obtain ZS-9 specific ligand to confirm tumor marker of non small-cell lung cancer. Methods: Artificially synthesize biotin labeled peptide ZS-9, anchored ZS-9 in the enzyme label plate coupled by avidin, used ZS-9 as probe to screen cDNA library of human lung cancer, after screening, obtained bacteriophage clone specifically binding with anchored polypeptide ZS-9. Extracted plasmid of bacteriophage and performed sequencing after amplified by PCR. Results: It was demonstrated by bioinformatic analysis on the sequence of ligand binded by lung cancer specific peptide ZS-9 that the ligand was the cytoskeletal protein periplakin on the surface of lung cancer cells, suggesting that periplakin might be a new marker for non-small-cell lung cancer in lung cancer. Conclusion: Use specific lung cancer binding peptide to screen new tumor marker periplakin in lung cancer and further studies on its biologic functions in genesis and development of lung cancer are still needed.

Application of phage display technology in targeted therapy of breast cancer

Phage display is a technology of gene expression and screening, it is widely used in the fields of defining antigen epitopes, signal transduction, genetic treatment, parasites research and tumor targeted therapy. Breast cancer is the most common cancer in women, we can obtain peptides specially associated with breast cancer by using phage display technology, and this method has great potential in early diagnosis of breast cancer and development new targeted drugs.

Plasma fibrinogen levels are associated with epidermal growth factor receptor gene mutation in Chinese patients with non-small cell lung cancer

Objective： The plasma fibrinogen levels had not only been used as an independent prognostic parameter for the patients with non-small cell lung cancer （NSCLC）, but also as a promising biomarker for evaluating the efficacy of chemotherapy. This study aimed to investigate the correlation between the plasma fibrinogen levels and epidermal growth factor receptor （EGFR） gene mutation and clinical-pathological characteristics of Chinese patients with NSCLC. Methods： In this retrospective study, NSCLC specimens collected from 352 patients between November 2009 and November 2011 were selected to detect EGFR gene mutation with real-time polymerase chain reaction （RT-PCR）. In these specimens, 308 ones were also detected EGFR gene copy number with fluorescence in situ hybridization （FISH）. Coagulation makers were examined prior to the operations. The association between the plasma fibrinogen levels and EGFR gene mutation and clinical-pathological characteristics were analyzed using SPSS 16.0 software. Results： The median pre-operation plasma fibrinogen level was 3.55 g/L （109/352） patients with higher plasma fibrinogen level （〉 4.0 g/L）. The lower plasma fibrinogen levels correlated significantly with EGFR gene mutations （P 〈 0.001）, the similar result was seen in platelet counts （P = 0.026）. A linear correlation was found between the plasma fibrinogen levels and the platelet counts in NSCLC patients （R^2 = 0.209, P 〈 0.001）. Pre-peration plasma fibrinogen levels correlated with gender （P 〈 0.001）, smoking status （P 〈 0.001 ）, and histology （P 〈 0.001 ）. There were significant link between the above clinical-pathological characteristics and EGFR gene mutations. In addition, EGFR gene mutation was correlated with FISH-positive status （P 〈 0.001）. Moreover, both plasma fibrinogen level （P = 0.024） and the EGFR gene copy number （P = 0.040） had significant relationships with the pathological TNM stage. Conclusion： This study showed that a significant relevance between plasma fibrinogen levels and EGFR gene mutations. The plasma fibrinogen level might be as a clinical decision parameter for evaluating the efficacy of anti-EGFR tyrosine kinase inhibitors （TKIs） in NSCLC. The patients of NSCLC had higher indicate have poor benefits from anti-EFGR TKIs. In addition, pre-operation plasma fibrinogen level could be used as an indepedent prognostic biomarker for the patients with NSCLC.

Sintilimab versus docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer:an open-label,randomized controlled phase 3 trial(ORIENT-3)

Background:Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer(sqNSCLC)after failure of first-line chemotherapy are limited.This study(ORIENT-3)aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC.Methods:ORIENT-3 was an open-label,multicenter,randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy.Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m^(2) of docetaxel intravenously every 3 weeks,stratified by the Eastern Cooperative Oncology Group performance status.The primary endpoint was overall survival(OS)in the full analysis set(FAS).Secondary endpoints included progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),duration of response(DoR)and safety.Results:Between August 25,2017,and November 7,2018,290 patients were randomized.For FAS,10 patients fromthe docetaxel armwere excluded.Themedian OS was 11.79(n=145;95%confidence interval[CI],10.28-15.57)months with sintilimab versus 8.25(n=135;95%CI,6.47-9.82)months with docetaxel(hazard ratio[HR]:0.74;95%CI,0.56-0.96;P=0.025).Sintilimab treatment significantly prolonged PFS(median 4.30 vs.2.79 months;HR:0.52;95%CI,0.39-0.68;P<0.001)and showed higher ORR(25.50%vs.2.20%,P<0.001)and DCR(65.50%vs.37.80%,P<0.001)than the docetaxel arm.The median DoRwas 12.45(95%CI,4.86-25.33)months in the sintilimab arm and 4.14(95%CI,1.41-7.23)months in the docetaxel arm(P=0.045).Treatment-related adverse events of grade≥3were reported in 26(18.1%)patients in the sintilimab arm and 47(36.2%)patients in the docetaxel arm.Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors,including OVOL2(HR:0.35;P<0.001)and CTCF(HR:3.50;P<0.001),for sintilimab treatment.Conclusions:Compared with docetaxel,sintilimab significantly improved the OS,PFS,and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.