Prognostic value of CYFRA 21 − 1 and Ki67 in advanced NSCLC patients with wild-type EGFR

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Abstract

Background

The prognostic value of cytokeratin 19 fragment (CYFRA 21 − 1) and Ki67 in advanced non-small cell lung cancer (NSCLC) patients with wild-type epidermal growth factor receptor (EGFR) remains to be explored.

Methods

In this study, 983 primary NSCLC patients from January 2016 to December 2019 were retrospectively reviewed. Finally, 117 advanced NSCLC patients with wild-type EGFR and 37 patients with EGFR mutation were included and prognostic value of CYFRA 21 − 1 and Ki67 were also identified.

Results

The patients age, smoking history and the Eastern Corporative Oncology Group (ECOG) performance scores were significantly different between CYFRA21-1 positive and negative groups ( p < 0.05), while no significant differences were found in Ki67 high and low groups. The results of over survival (OS) demonstrated that patients with CYFRA21-1 positive had markedly shorter survival time than CYFRA21-1 negative ( p < 0.001, For whole cohorts; p = 0.002, For wild-type EGFR). Besides, patients with wild-type EGFR also had shorter survival times than Ki67 high group. Moreover, In CYFRA 21 − 1 positive group, patients with Ki67 high had obviously shorter survival time compared to patients with Ki67 low (median: 24vs23.5 months; p = 0.048). However, Ki67 could not be used as an adverse risk factor for patients with EGFR mutation. Multivariate cox analysis showed that age (HR, 1.031; 95%CI, 1.003 ~ 1.006; p = 0.028), Histopathology (HR, 1.760; 95%CI,1.152 ~ 2.690; p = 0.009), CYFRA 21 − 1 (HR, 2.304; 95%CI,1.224 ~ 4.335; p = 0.01) and Ki67 (HR, 2.130; 95%CI,1.242 ~ 3.652; p = 0.006) served as independent prognostic risk factor for advanced NSCLC patients.

Conclusions

Our finding indicated that CYFRA 21 − 1 was an independent prognostic factor for advanced NSCLC patients and Ki67 status could be a risk stratification marker for CYFRA 21 − 1 positive NSCLC patients with wild-type EGFR.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12885-023-10767-9.

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Most cited references 28

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Cancer statistics, 2020

Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2020)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.

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Tumour burden and efficacy of immune-checkpoint inhibitors

Filippo Dall’Olio, Aurélien Marabelle, Caroline Caramella … (2021)

Accumulating evidence suggests that a high tumour burden has a negative effect on anticancer immunity. The concept of tumour burden, simply defined as the total amount of cancer in the body, in contrast to molecular tumour burden, is often poorly understood by the wider medical community; nonetheless, a possible role exists in defining the optimal treatment strategy for many patients. Historically, tumour burden has been assessed using imaging. In particular, CT scans have been used to evaluate both the number and size of metastases as well as the number of organs involved. These methods are now often complemented by metabolic tumour burden, measured using the more recently developed 2-deoxy-2-[18F]-fluoro-D-glucose (FDG)-PET/CT. Serum-based biomarkers, such as lactate dehydrogenase, can also reflect tumour burden and are often also correlated with a poor response to immune-checkpoint inhibitors. Other circulating markers (such as circulating free tumour DNA and/or circulating tumour cells) are also attracting research interest as surrogate markers of tumour burden. In this Review, we summarize evidence supporting the utility of tumour burden as a biomarker to guide the use of immune-checkpoint inhibitors. We also describe data and provide perspective on the various tools used for tumour burden assessment, with a particular emphasis on future therapeutic strategies that might address the issue of inferior outcomes among patients with cancer with a high tumour burden.

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Lung Cancer Staging and Prognosis.

Gavitt A Woodard, Kirk D Jones, David M Jablons (2016)

The seventh edition of the non-small cell lung cancer (NSCLC) TNM staging system was developed by the International Association for the Staging of Lung Cancer (IASLC) Lung Cancer Staging Project by a coordinated international effort to develop data-derived TNM classifications with significant survival differences. Based on these TNM groupings, current 5-year survival estimates in NSLCC range from 73 % in stage IA disease to 13 % in stage IV disease. TNM stage remains the most important prognostic factor in predicting recurrence rates and survival times, followed by tumor histologic grade, and patient sex, age, and performance status. Molecular prognostication in lung cancer is an exploding area of research where interest has moved beyond TNM stage and into individualized genetic tumor analysis with immunohistochemistry, microarray, and mutation profiles. However, despite intense research efforts and countless publications, no molecular prognostic marker has been adopted into clinical use since most fail in subsequent cross-validation with few exceptions. The recent interest in immunotherapy for NSCLC has identified new biomarkers with early evidence that suggests that PD-L1 is a predictive marker of a good response to new immunotherapy drugs but a poor prognostic indicator of overall survival. Future prognostication of outcomes in NSCLC will likely be based on a combination of TNM stage and molecular tumor profiling and yield more precise, individualized survival estimates and treatment algorithms.

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Author and article information

Contributors

Jian-Bo He: 593686765@qq.com

Xiao-Qun Zheng: jszhengxq@163.com

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date (Electronic): 31 March 2023

Publication date PMC-release: 31 March 2023

Publication date Collection: 2023

Volume: 23

Electronic Location Identifier: 295

Affiliations

[1 ]GRID grid.417384.d, ISNI 0000 0004 1764 2632, Department of Laboratory Medicine, , The Second Affiliated and Yuying Children’s Hospital of Wenzhou Medical University, ; Wenzhou, China

[2 ]GRID grid.268099.c, ISNI 0000 0001 0348 3990, School of Laboratory Medicine and Life Sciences, The Key Laboratory of Laboratory Medicine, , Wenzhou Medical University, Ministry of Education of China, ; Wenzhou, China

[3 ]GRID grid.417384.d, ISNI 0000 0004 1764 2632, Department of Respiratory Medicine, , The Second Affiliated and Yuying Children’s Hospital of Wenzhou Medical University, ; Wenzhou, China

Article

Publisher ID: 10767

DOI: 10.1186/s12885-023-10767-9

PMC ID: 10064697

PubMed ID: 37004004

SO-VID: 90bde732-d3a4-42e6-b2c5-3eebac69fb3a

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 23 April 2022

Date accepted : 23 March 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100004731, Natural Science Foundation of Zhejiang Province;

Award ID: LY18H200006

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cyfra 21 − 1,ki67,nsclc,wild-type egfr,prognosis

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cyfra 21 − 1, ki67, nsclc, wild-type egfr, prognosis

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Prognostic value of CYFRA 21 − 1 and Ki67 in advanced NSCLC patients with wild-type EGFR

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Abstract

Background

Methods

Results

Conclusions

Supplementary Information

Related collections

Karger: Oncology

Most cited references 28

Cancer statistics, 2020

Tumour burden and efficacy of immune-checkpoint inhibitors

Lung Cancer Staging and Prognosis.

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