The Prognostic Value of Preoperative Serum Tumor Markers in Non-Small Cell Lung Cancer Varies With Radiological Features and Histological Types

Chen, Haiqing; Fu, Fangqiu; Zhao, Yue; Wu, Haoxuan; Hu, Hong; Sun, Yihua; Zhang, Yawei; Xiang, Jiaqing; Zhang, Yang

doi:10.3389/fonc.2021.645159

Cited by 11 publications

(10 citation statements)

References 58 publications

(61 reference statements)

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“…Presently, only a few circulating protein-based biomarkers with relatively low specificities (e.g., cytokeratin 19 fragment (CYFRA 21-1, specificity 76%), carcinoma embryonic antigen (CEA, specificity 52%), carbohydrate antigen 125 (CA125, specificity 52%), carbohydrate antigen 153 (CA153), carbohydrate antigen 199 (CA199) and neuron-specific enolase (NSE, specificity 22%)) have been incorporated into clinical practice for NSCLC [51][52][53][54][55][56]. However, as single markers their prognostic value is controversially discussed, and their use is often limited to certain tumor subtypes [57].…”

Section: Discussionmentioning

confidence: 99%

Hsp70 in Liquid Biopsies—A Tumor-Specific Biomarker for Detection and Response Monitoring in Cancer

Werner

Stangl

Salvermoser

et al. 2021

Cancers

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In contrast to normal cells, tumor cells of multiple entities overexpress the Heat shock protein 70 (Hsp70) not only in the cytosol, but also present it on their plasma membrane in a tumor-specific manner. Furthermore, membrane Hsp70-positive tumor cells actively release Hsp70 in small extracellular vesicles with biophysical characteristics of exosomes. Due to conformational changes of Hsp70 in a lipid environment, most commercially available antibodies fail to detect membrane-bound and vesicular Hsp70. To fill this gap and to assess the role of vesicular Hsp70 in circulation as a potential tumor biomarker, we established the novel complete (comp)Hsp70 sandwich ELISA, using two monoclonal antibodies (mAbs), that is able to recognize both free and lipid-associated Hsp70 on the cell surface of viable tumor cells and on small extracellular vesicles. The epitopes of the mAbs cmHsp70.1 (aa 451–461) and cmHsp70.2 (aa 614–623) that are conserved among different species reside in the substrate-binding domain of Hsp70 with measured affinities of 0.42 nM and 0.44 nM, respectively. Validation of the compHsp70 ELISA revealed a high intra- and inter-assay precision, linearity in a concentration range of 1.56 to 25 ng/mL, high recovery rates of spiked liposomal Hsp70 (>84%), comparable values between human serum and plasma samples and no interference by food intake or age of the donors. Hsp70 concentrations in the circulation of patients with glioblastoma, squamous cell or adeno non-small cell lung carcinoma (NSCLC) at diagnosis were significantly higher than those of healthy donors. Hsp70 concentrations dropped concomitantly with a decrease in viable tumor mass upon irradiation of patients with approximately 20 Gy (range 18–22.5 Gy) and after completion of radiotherapy (60–70 Gy). In summary, the compHsp70 ELISA presented herein provides a sensitive and reliable tool for measuring free and vesicular Hsp70 in liquid biopsies of tumor patients, levels of which can be used as a tumor-specific biomarker, for risk assessment (i.e., differentiation of grade III vs. IV adeno NSCLC) and monitoring of therapeutic outcomes.

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Section: Discussionmentioning

confidence: 99%

Hsp70 in Liquid Biopsies—A Tumor-Specific Biomarker for Detection and Response Monitoring in Cancer

Werner

Stangl

Salvermoser

et al. 2021

Cancers

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“…Serum tumor markers have been widely used in the diagnosis, efficacy evaluation, and prognosis evaluation of lung cancer. Of these, serum CEA and Cyfra21‐1 are the most widely markers used in the diagnosis of lung cancer, while SCCA levels are often elevated in SCCs 24 . In our cohort, the preoperative detection of three serum tumor markers in patients found that only a few patients had elevations.…”

Section: Discussionmentioning

confidence: 64%

Clinicopathological features and survival of rare primary pulmonary lymphoepithelial carcinoma: A cohort from a single center

Nie

Tao

Zhu

et al. 2023

Journal of Surgical Oncology

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BackgroundPrimary pulmonary lymphoepithelial carcinoma (PLEC) is a rare subtype of nonsmall cell lung cancer. This study aimed to investigate the clinicopathological and prognostic characteristics of resected primary PLEC.Materials and MethodsIn this retrospective study, 95 consecutive patients with primary PLEC, who received radical surgical resection treatment, were examined from October 2009 to January 2022. The clinicopathological features and their association with survival outcomes were analyzed.ResultsPrimary PLEC predominated in relatively younger patients and nonsmokers, who lacked driver mutations and were always positive for immunohistochemical markers of the squamous cell lineage. Further, 21.1% of patients had abnormally elevated preoperative serum marker fragments of cytokeratin 19 (Cyfra21‐1). The median follow‐up time was 43.5 months. The 1‐, 3‐, and 5‐year recurrence‐free survival (RFS) rates were 96.5%, 81.8%, and 64.3%, respectively. The median RFS time was not reached. Cox univariate survival analysis showed that patients with positive lymph nodes had significantly worse RFS than those with negative ones (p = 0.017). The patients with open surgery experienced significantly worse RFS than those with video‐assisted thoracoscopic surgery (p = 0.038). The multivariate survival analysis confirmed that only lymph node involvement (hazard ratio: 2.769; 95% confidence interval: 1.171–6.548, p = 0.020) was an independent prognostic factor.ConclusionsPrimary PLEC is a rare type of lung cancer with a favorable outcome, more common in young and nonsmoking Asian populations. Driver gene mutations are rare. Regional lymph node metastasis is an independent prognostic factor for RFS after radical surgical resection.

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“…The prognostic utility of different serological markers in lung cancer has been evidenced by different authors. For instance, Chen et al ( 77 ) evaluated the preoperative levels of the serological markers CEA, CYFRA21-1, NSE, CA 19-9, CA 153 and CA125 in 2,654 patients with NSCLC who were candidates for resection surgery, demonstrating how high levels of CEA, CYFRA 21-1 or CA125 are associated with unfavorable survival and higher rates of recurrence. In this light, Bes-Scartezini and Saad Junior ( 78 ) determined that in 112 patients with non-squamous NSCLC, elevation of CA125 or Ca15-3 was associated with unfavorable survival ( 77 , 78 ).…”

Section: Serological Markersmentioning

confidence: 99%

Exploring histopathological and serum biomarkers in lung adenocarcinoma: Clinical applications and translational opportunities (Review)

et al. 2022

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Lung cancer represents one of the most common neoplasms and the main cause of cancer-associated death worldwide. Its relationship with different risk factors such as tobacco, which is its main etiological factor, has been clearly established and despite the numerous advances achieved in the diagnosis, treatment and follow-up of these patients, the life expectancy of these patients is notably limited. Furthermore, its treatment is not exempt from comorbidities and frequently it neither provides optimal control of the disease nor improve the quality of life of these patients. Despite the possibility of performing screening tests in patients at risk, their implementation in daily clinical practice is complex and most of them are diagnosed at an advanced stage of their disease where systemic radiotherapy or chemotherapy treatments slightly improve their prognosis. Lung adenocarcinoma is the most representative type of lung cancer, with specific epidemiological, molecular and clinical features. Thus, a growing number of studies are being conducted to find potential therapeutic targets based on the study of different molecular pathways, improving the outcome for these patients. In addition, a broad spectrum of serological, immunohistochemical and genetic markers are being evaluated for use in the screening and follow-up of these patients in daily clinical practice, but unlike for other tumors, they are currently not implemented in the early diagnosis of the disease. Therefore, the aim of the present review was to summarize the main advances that have occurred in the development of serological and histological markers and their therapeutic implications in patients diagnosed with lung adenocarcinoma, explaining the limitations that have been observed and analyzing the future perspectives in the clinical management of this disease. Contents 1. Introduction 2. Molecular and histological markers in lung cancer 3. Serological markers 4. Circulating tumor cells 5. MicroRNAs 6. Conclusions

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The Prognostic Value of Preoperative Serum Tumor Markers in Non-Small Cell Lung Cancer Varies With Radiological Features and Histological Types

Cited by 11 publications

References 58 publications

Hsp70 in Liquid Biopsies—A Tumor-Specific Biomarker for Detection and Response Monitoring in Cancer

Hsp70 in Liquid Biopsies—A Tumor-Specific Biomarker for Detection and Response Monitoring in Cancer

Clinicopathological features and survival of rare primary pulmonary lymphoepithelial carcinoma: A cohort from a single center

Exploring histopathological and serum biomarkers in lung adenocarcinoma: Clinical applications and translational opportunities (Review)

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