scholarly journals Costimulatory Molecule Expression Profile as a Biomarker to Predict Prognosis and Chemotherapy Response for Patients With Small-cell Lung Cancer

2021 ◽  
Author(s):  
Zhihui Zhang ◽  
Peng Wu ◽  
Zhaoyang Yang ◽  
Chaoqi Zhang ◽  
Yuejun Luo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Expression Profile ◽  
Cell Lung Cancer ◽  
Costimulatory Molecule ◽  
Costimulatory Molecules ◽  
Small Cell ◽  
Chemotherapy Response ◽  
Small Cell Lung ◽  
Independent Cohort

Abstract Background: Small cell lung cancer (SCLC) is the deadliest pathological subtype of lung cancer with few precise treatment options. Owing to the paucity of specimens, progress in identifying prognostic and therapeutic biomarkers for SCLC has been stagnant for decades. Considering the costimulatory molecules are essential elements in modulating anti-tumor immune responses and determining therapeutic response, we decided to conduct a comprehensive analyses of costimulatory molecule expression profile with regard to prognosis and chemotherapy response for SCLCs for the first time. Methods: We systematically explored the molecular characteristics and clinical relevance of costimulatory molecules in SCLC. Using a univariate Cox and LASSO Cox model, we then constructed a molecule-based signature (CMS) based on our examination of 208 cases with SCLC from two different cohorts—including an independent cohort that contained 131 cases with qPCR data, to predict the outcome and chemotherapy response for SCLCs. Relationships between the CMS and adjuvant chemotherapy (ACT) benefits and inflammatory landscape were also evaluated.Results: We found T cell activation was restrained in SCLCs, and costimulatory molecules exhibited widespread abnormal genetic alterations and expression. Then, the CMS containing 7 molecules (ICOSLG, EDA2R, TNFRSF25, CD276, RELT, PDCD1, and TNFSF14) was built with a training cohort of 77 cases, which successfully divided patients into high- or low-risk groups with significantly different prognosis and chemotherapy benefit (both P<0.001). The CMS was well validated in the independent cohort with qPCR data. ROC and C-index analysis confirmed the superior predictive performance of the CMS in comparison with other clinicopathological parameters from different cohorts. Importantly, the CMS was confirmed as a significantly independent prognosticator for clinical outcomes and chemotherapy response in SCLCs through multivariate Cox analysis. Further analysis revealed that low-risk patients were characteristic by an activated immune phenotype with distinct expression of immune checkpoints.Conclusions: We firstly uncovered the expression heterogeneity of costimulatory molecules in SCLC, and successfully constructed a novel predictive CMS. The identified signature contributed to more accurate patient stratification and provided robust prognostic value in estimating survival and the clinical response to chemotherapy, allowing optimization of treatment and prognosis management for patients with SCLC.

scholarly journals An Immune-related Lncrna Signature Predicts Prognosis and Adjuvant Chemotherapeutic Response in Patients With Small-cell Lung Cancer

2021 ◽  
Author(s):  
Zhihui Zhang ◽  
Yuejun Luo ◽  
Chaoqi Zhang ◽  
Peng Wu ◽  
Guochao Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Expression Profiles ◽  
Small Cell ◽  
Low Risk ◽  
Chemotherapy Response ◽  
Clinical Parameters ◽  
Small Cell Lung ◽  
Independent Cohort

Abstract BackgroundPatients with small-cell lung cancer (SCLC) are burdened by limited treatment options and the disease’s dismal prognosis. Long non-coding RNAs (lncRNAs) are essential regulators of genetic alteration and are actively involved in tumor immunity. However, owing to the paucity of specimens, few studies have examined the interaction between immune genes and lncRNAs in SCLCs. MethodsThe immune-related lncRNAs (irlncRNAs) expression profiles and clinical significance were comprehensively explored. We enrolled 227 patients with SCLC, including 79 cases from GSE65002 and 148 cases from an independent cohort with corresponding qPCR data. A least absolute shrinkage and selection operator (LASSO) was performed to identify the most prognostic irlncRNAs to construct an irlncRNAs-based signature in SCLC. We additionally investigated the potential and immune landscapes of the signature using bioinformatic methods. ResultsTotally, 316 irlncRNAs were filtered out in SCLCs. Then, an 8-irlncRNAs-based signature (ENOX1-AS1, AC005162, LINC00092, RPL34-AS1, AC104135, AC015971, AC126544, and AP001189) was established for patients with SCLC in the training cohort. The classifier successfully divided patients into high- or low-risk groups with dramatically different survival rates and chemotherapy benefit (both P<0.001). The signature was also well-validated in an independent cohort and various clinical subgroups. Compared to other important clinical parameters, this signature exhibited superior predictive performance for chemotherapy response and prognosis. Importantly, the signature also acts as an independent prognostic factor in the two cohorts after adjusting with other clinical parameters. Interestingly, functional analysis revealed that multiple activated immune-related pathways were abundant in the low-risk group. Additionally, the signature was found closely associated with inflammatory responses and various immune checkpoints. ConclusionWe constructed the first irlncRNAs-based signature for prognosis and survival benefit of chemotherapy outcome prediction for patients with SCLC. The irlncRNAs signature was a reliable and robust prognostic classifier that could be useful for clinical management and determination of potential chemotherapy benefit for patients with SCLC.

scholarly journals Reduction of Elevated Plasma Osteopontin Levels With Resection of Non–Small-Cell Lung Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 936-941 ◽  
Author(s):  
Justin D. Blasberg ◽  
Harvey I. Pass ◽  
Chandra M. Goparaju ◽  
Raja M. Flores ◽  
Suzie Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Independent Cohort

Purpose Plasma osteopontin (OPN) levels in advanced non–small-cell lung cancer (NSCLC) correlate with therapeutic response and survival, but the utility of plasma OPN for diagnosis and monitoring of early-stage NSCLC has not been investigated. We hypothesize that plasma OPN levels are elevated in early-stage NSCLC and decrease with resection. Patients and Methods Presurgery plasma OPN levels (in ng/mL) were measured by enzyme-linked immunosorbent assay (ELISA) in a discovery set of 60 patients with early-stage NSCLC and were compared with data from 56 cancer-free smokers. Presurgery OPN was validated in an independent cohort of 96 patients with resectable NSCLC. The presurgery levels in the latter cohort were compared with matched postsurgery levels. Perioperative OPN levels were correlated with demographics, tumor characteristics, and perioperative events. OPN was monitored during follow-up. Results Discovery set presurgery NSCLC OPN (271 ± 31 ng/mL) was higher than smokers (40 ± 2 ng/mL; P = .001). Presurgery OPN was similar in the NSCLC validation cohort (324 ng/mL ± 20 ng/mL; P = .134). Postsurgery OPN (256 ng/mL ± 21 ng/mL) measured at mean of 9.8 weeks (range, 2 to 46 weeks) was lower than presurgery OPN (P = .005). Time from surgery significantly impacted postsurgery OPN: OPN ≤ 6 weeks postsurgery (303 n/mL ± 26 ng/mL) was higher than OPN greater than 6 weeks postsurgery (177 ng/mL ± 29 ng/mL; P = .003). Multivariate analysis noted correlations between albumin and creatinine to presurgery OPN and use of thoracotomy to postsurgery OPN. Recurrence rate was 5% at 29 weeks mean follow-up. OPN at recurrence was elevated from postsurgery nadir. Conclusion Plasma OPN levels are elevated in early-stage NSCLC. They are reduced after resection and appear to increase with recurrence. Plasma OPN may have utility as a biomarker in early-stage NSCLC.

scholarly journals Microarray expression profile of long non-coding RNAs in EGFR-TKIs resistance of human non-small cell lung cancer

2014 ◽  
Vol 33 (2) ◽  
pp. 833-839 ◽  
Author(s):  
NINGNING CHENG ◽  
XUEFEI LI ◽  
CHAO ZHAO ◽  
SHENGXIANG REN ◽  
XIAOXIA CHEN ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Expression Profile ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Non Coding Rnas ◽  
Microarray Expression ◽  
Microarray Expression Profile ◽  
Egfr Tkis

Differential expression profile of MAGE family in non-small-cell lung cancer

Lung Cancer ◽  
2007 ◽  
Vol 56 (2) ◽  
pp. 185-192 ◽  
Author(s):  
Jong-Rung Tsai ◽  
Inn-Wen Chong ◽  
Yan-Hua Chen ◽  
Ming-Je Yang ◽  
Chau-Chyun Sheu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Differential Expression ◽  
Expression Profile ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Differential Expression Profile

Phase II study of docetaxel and S-1 combination therapy in patients with previously treated non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18122-18122
Author(s):  
S. Atagi ◽  
M. Kawahara ◽  
A. Kubo ◽  
T. Kawaguchi ◽  
K. Yumine ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Controlled Trial ◽  
Small Cell ◽  
Stage Iiib ◽  
Chemotherapy Response ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

18122 Background: Docetaxel is active against chemotherapy-pretreated non-small-cell lung cancer (NSCLC). S-1 is a novel oral fluoropyrimidine, composed of tegafur, 5-chloro-2,4-dihydroxypyridine (dihydropyrimidinedehydrogenase inhibitor), and potassium oxonate (orotate phosphoribosyl transferase inhibitor). It has been commercially available and used for NSCLC in Japan. We conducted this study to evaluate the efficacy and safety of docetaxel combined with S-1 in NSCLC patients (pts) who were previously treated with one or more regimens. Methods: Eligible pts were required to have histologically or cytologically confirmed measurable or evaluable stage IIIB or IV NSCLC, age= 20 years, one or more previous chemotherapy, a performance status (PS) 0–1, and adequate organ function and bone marrow reserve. In this study, pts received S-1 (80 mg/m2 orally on days 1–14) and docetaxel (40mg/m2 IV on days 1). Treatment was repeated every 3 weeks. Results: Between January 2005 and May 2006, 30 pts were enrolled on this study. 29 pts were eligible and evaluable. Median age was 67 (48–79), male/female (23/6), PS 0/1 (9/20), stage IIIB/IV (7/22), and prior chemotherapy regimen 1/2/3 (23/4/2). 28 pts received a platinum-based chemotherapy. Response: PR=7(24%), SD=13, PD=7, NE=2. Median survival time was 10.2 months. Grade 3/4 toxicities (% of pts) were as follows: leukocytes 6/0 (20.6%), neutrophils 7/3 (34.4%), platelets 0/0, infection 0/1 (3.4%), fever 2/0 (6.9%), diarrhea 1/0 (3.4%), neurology 0/1 (3.4%), and mucositis 1/0 (3.4%). There were no treatment-related deaths. Conclusions: The combination of docetaxel and S-1 was effective with acceptable toxicity in pts with previously treated NSCLC. These results warrant further investigations of this regimen a randomized controlled trial as a second-line treatment for NSCLC. No significant financial relationships to disclose.

Predicting Chemotherapy Response to Paclitaxel-Based Therapy in Advanced Non-Small-Cell Lung Cancer (Stage IIIb or IV) with a Higher T Stage (> T2)

Oncology ◽  
2002 ◽  
Vol 63 (2) ◽  
pp. 173-179 ◽  
Author(s):  
Wu-Huei Hsu ◽  
Ruoh-Fang Yen ◽  
Chia-Hung Kao ◽  
Shih-Chih Shiun ◽  
Nan-Yung Hsu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iiib ◽  
Chemotherapy Response ◽  
Cancer Stage ◽  
Small Cell Lung ◽  
T Stage

scholarly journals Prognostic Factors in Advanced Non-Small-Cell Lung Cancer Patients: Patient Characteristics and Type of Chemotherapy

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Salah Abbasi ◽  
Ahmed Badheeb
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Smoking Status ◽  
Performance Status ◽  
Forced Expiratory Volume ◽  
Small Cell ◽  
Chemotherapy Response ◽  
Small Cell Lung

Eleven prognostic factors were retrospectively analyzed in 270 newly diagnosed patients with advanced non-small-cell lung cancer including age, sex, performance status, histology, stage, smoking status, hemoglobin level, forced expiratory volume in one second (FEV1), weight loss >5% in 3 months preceding therapy, number of involved organs, and type of first-line chemotherapy. Response rate was 35.6%, and median survival was 8.2 months (95% CI, 7.8 to 8.7) for the whole group. Age ≤60 years (), (), and the use of platinum/docetaxel () were significantly associated with an improved survival. Histology did not affect outcome in the absence of targeted therapies.

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