Cancer Biomarkers - Volume 23, issue 3

Authors: Kuroda, Hiroaki | Yoshida, Tatsuya | Arimura, Takaaki | Mizuno, Tetsuya | Sakakura, Noriaki | Yatabe, Yasushi | Sakao, Yukinori

Article Type: Research Article

Abstract: BACKGROUND: One of the known risk factors for non-small cell lung cancer (NSCLC) is somatic mutation in the Kirsten rat sarcoma (KRAS ) gene. The relationship with smoking is well known. METHODS: We retrospectively studied the data of 92 patients who underwent pulmonary resection January 2003 and June 2012 and were diagnosed as KRAS -mutated pathological stage I adenocarcinoma. RESULTS: Among them, 33 patients who were non to light smoker (NLS) (smoking index, 0 to 400) were compared with 59 middle to heavy smoker (MHS) (> 400). The 5-year overall survival (OS) …was significantly better in NLS (96.9%) than in MHS (80.0%); however, no significant difference was observed compared with wild-type KRAS (92.8%) (p = 0.66). The presence of p53 was significantly associated with smoking history (p < 0.01). The 5-year OS for NLS with p53 -negative KRAS codon 12-mutated NSCLC (n = 28) was significantly better (96.3%) than that for MHS with both p53 -positive and -negative KRAS mutation (p = 0.03 and p < 0.03, respectively). CONCLUSIONS: A non to light smoking habit might contribute to an improvement in prognosis that is equivalent to that of wild-type KRAS , and p53 mutation did not affect survival in smokers harboring KRAS codon 12. Show more

Keywords: NSCLC, KRAS, smoking, clinical stage I, codon 12

DOI: 10.3233/CBM-181483

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 419-426, 2018

Authors: Zhang, Hao | He, Bin | Cui, Jun | Zhao, Mingzhang | Zhang, Zengwang

Article Type: Research Article

Abstract: PURPOSE: The need for less invasive procedures for lung cancer probing is critically needed to better understand the disease. The purpose of the current study aims to explore the use of circulating tumor DNA (ctDNA) derived from plasma and urine specimens. METHODS: Matched peripheral blood and morning urine specimens were obtained from 160 late stage NSCLC patients. The amount of ctDNA was quantified for each of the patients. Activating and sensitizing EGFR mutations commonly found in NSCLC patients were profiled. Longitudinal analysis was performed to compared DNA variations during disease progression. RESULTS: Measurement …of EGFR mutations in NSCLC patients using plasma and urinal DNA demonstrated strong concordance to conventional tissue biopsy profiling. Baseline matched tumor samples yielded 82.8% and 84.0% for plasma and urinal DNA respectively. For these measurements, the positive predictive value was 100% for plasma and urinal DNA. In the longitudinal study, we observed strong links to disease severity and survival analysis showed a clear trend with patients having higher DNA concentrations to have worse outcome especially for urinal DNA. HR for patients stratified using plasma and urinal DNA were 1.23 and 2.55 respectively. CONCLUSION: Measurements of circulating DNA within body fluids presented potentially new tools for the disease management of NSCLC patients with EGFR mutations. We demonstrated both plasma and urinal DNA correlated well to tissue biopsies and were potentially prognostic to address patients’ survival outcome. Show more

Keywords: NSCLC, ctDNA, EGFR, T790M, plasma DNA, urinal DNA

DOI: 10.3233/CBM-181511

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 427-436, 2018

Authors: Feng, Runhua | Sah, Birendra K. | Li, Jianfang | Lu, Sheng | Yuan, Fei | Jin, Xiaolong | Yan, Min | Liu, Bingya | Li, Chen | Zhu, Zhenggang

Article Type: Research Article

Abstract: BACKGROUND: Few biomarkers are available for the prediction of prognosis and recurrence in lymph node (LN)-negative gastric cancer (GC) currently. miR-126 functions as a tumor suppressor in GC, however, its clinical significance in LN-negative GC remains unknown. AIM: To investigate the associations of tissue miR-126 level with the clinicopathological characteristics and clinical outcome of LN-negative GC patients. METHODS: Quantitative real-time polymerase chain reaction was performed to examine the tissue miR-126 level in 315 LN-negative GC patients who underwent curative gastrectomy with D2 lymphadenectomy. The associations of tissue miR-126 level with clinicopathological characteristics and …clinical outcome were evaluated. RESULTS: Compared with matched adjacent non-tumor tissues, miR-126 expression was significantly down-regulated in tumor tissues. A reduced tissue miR-126 level statistically correlated with aggressive clinicopathological characteristics, including larger tumor size, deeper local invasion, and poorer prognosis. Notably, multivariate analysis identified advanced T stage and low miR-126 level as independent predictors of the unfavorable prognosis and recurrence of LN-negative GC. CONCLUSIONS: These results indicate for the first time that advanced T stage and low miR-126 level are predictors of unfavorable prognosis and recurrence in LN-negative GC patients. These parameters should be taken into account to stratify patients for adjuvant therapy and close follow-up. Show more

Keywords: Gastric cancer, lymph node negative, prognosis, recurrence, miR-126

DOI: 10.3233/CBM-181526

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 437-445, 2018

Authors: Song, Tiejun | Yan, Lei | Cai, Kerui | Zhao, Tianshu | Xu, Meiling

Article Type: Research Article

Abstract: BACKGROUND: Drug resistance in clinical cancer treatment has become an issue. OBJECTIVE: We focus on abnormally expressed lncRNAs in glioma and investigating the function of PVT1. METHODS: The paclitaxel-resistant glioma cells SHG-44 RE was obtained through screening the SHG 44 cells that were cultured in medium containing a certain concentration of paclitaxel. Cell survival of SHG 44 RE and SHG 44 cells under the treatment of paclitaxel was detected by MTT assay. The aberrant expressed lncRNAs were screened out with microarray analysis. Further qRT-PCR was utilized to validate the expression of lncRNA PVT1 in the two …cells. After manipulating the expression of PVT1, cell viability and apoptosis were measured by MTT and flow cytometry respectively. RESULTS: LncRNA PVT1 was overexpressed in glioma cells SHG-44 RE compared with parent SHG-44 cells. Down-regulation of lncRNA PVT1 inhibited the SHG-44 RE cell viability and increased glioma SHG-44 RE cells apoptosis after paclitaxel treatment, suggesting that inhibition of lncRNA PVT1 improved paclitaxel sensibility in human glioma cells. CONCLUSION: Down-regulation of PVT1 could enhance chemosensitivity of paclitaxel, induce apoptosis of glioma cells and noteworthy inhibit glioma cells proliferation. Our findings of PVT1 could contribute to attenuate paclitaxel resistance in clinical medicine. Show more

Keywords: Glioma, lncRNA, PVT1, paclitaxel resistance

DOI: 10.3233/CBM-181573

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 447-453, 2018

Authors: Guo, Liyin | Chen, Li | Wang, Hongxiang

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to explore the correlation of CD45 expression with clinicopathological features and treatment outcomes in elderly acute myeloid leukemia (AML) patients. METHODS: One hundred and twenty one elderly patients with de novo AML were consecutively recruited in this prospective cohort study, bone marrow samples from all patients were collected and CD45 expression were measured with flow cytometry. Complete remission (CR), event-free survival (EFS) and overall survival (OS) were evaluated. The median follow-up duration was 15.0 (range 2.0–36.0) months. RESULTS: CD45 high expression (CD45 high ) was …associated with higher risk stratification in elderly AML patients (P = 0.021). The percentage of CD45 high cases in CR patients was 16.4%, which was lower compared to non-CR patients (35.2%, P = 0.017), while no difference in percentage of CD45 high cases was found between allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients and non-allo-HSCT patients (16.7% vs. 25.7%, P = 0.492). As to survival profiles, median EFS in CD45 high patients was 6.0 (95% CI: 2.9–9.1) months, which was shorter than that in CD45 low expression (CD45 low ) patients (10.0 (95% CI: 7.2–12.8) months) (P = 0.002), and OS in CD45 high patients was 16.0 (95% CI: 13.4–18.6) months, which was worse compared to CD45 low patients (22.0 (95% CI: 17.0–27.0) months) (P = 0.010). In subgroup analysis, no difference of EFS and OS was found between CD45 high patients and CD45 low patients in favorable, intermediate or adverse risk subgroups. CONCLUSIONS: CD45 correlates with adverse risk stratification, decreased treatment response and unfavorable survival profiles in elderly AML patients. Show more

Keywords: Acute myeloid leukemia, elderly, CD45, prognosis

DOI: 10.3233/CBM-181602

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 455-463, 2018

Article Type: Other

DOI: 10.3233/CBM-179987

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 465-467, 2018