Biomarkers in Lung Cancer
Haryati1*, Holly Diany1
1Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Lambung Mangkurat University/Ulin General Hospital, Banjarmasin
*Corresponding Author: [email protected]
Abstract
Lung cancer is described as one of the leading causes of cancer related deaths worldwide and causes around 1.6 million deaths every year. Lung cancer was classified into two groups based on its biology, histology, therapy and prognosis, namely Small Cell Lung Cancer (SCLC) and Non- Small Cell Lung Carcinoma (NSCLC). Lung cancer patients are often late to be diagnosed earlier because they already have metastasis and made treatment options are limited causing the prognosis worse and the patient’s survival rate low. Biomarkers have an important role in lung cancer. The biomarkers of cancer are present in tumor or serum tissue and cover a wide variety of molecules, including DNA, mRNA, enzymes, metabolites, transcription factors, and cell surface receptors. It can help in establishing early diagnoses so as to improve prognostics and predict responses to various therapies in lung cancer patients.
Keywords: Biomarkers, Lung Cancer, NSCLC, SCLC
Abstrak
Kanker paru merupakan salah satu penyebab utama kematian terkait kanker di seluruh dunia dan sekitar 1,6 juta kematian terjadi di setiap tahunnya. Kanker paru diklasifikasikan menjadi dua kelompok secara biologi, histologi, terapi dan prognosisnya, yaitu Small Cell Lung Cancer (SCLC) dan Non-Small Cell Lung Carcinoma (NSCLC). Pasien dengan kanker paru sering terlambat untuk didiagnosis secara dini karena telah mengalami metastasis sehingga pilihan pengobatan menjadi terbatas dan menyebabkan prognosis menjadi buruk dan tingkat kelangsungan hidup pasien menjadi rendah. Biomarker memiliki peranan penting pada kanker paru. Biomarker kanker terdapat dalam jaringan tumor atau serum dan mencakup luas berbagai molekul, termasuk DNA, mRNA, enzim, metabolit, faktor transkripsi, dan reseptor permukaan sel. Dengan adanya biomarker baru diharapkan membantu diagnosis dini sehingga meningkatkan prognostik dan memprediksi respon terapi pada pasien kanker paru.
Kata kunci: Biomarker, Kanker Paru, NSCLC, SCLC
Introduction
Lung cancer is a malignant tumor of the lung originating from the bronchial epithelium, bronchioles, and alveoli. Lung cancer is described as one of the leading causes of cancer related deaths worldwide and causes around 1.6 million deaths every year.1 Globocan data in 2018 showed the incidence of lung cancer in the world was 2,094 million (11.6% of all cancers) and lung cancer mortality in the world was 1.8 million (18.4% of all cancer-related deaths).1
According to WHO in 2015, lung cancer was classified into two groups based on its biology, histology, therapy and prognosis, namely Small Cell Lung Cancer (SCLC) and Non- Small Cell Lung Carcinoma (NSCLC). NSCLC is around 85% and another 15% is SCLC of all lung cancer cases. The most common subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. These lung cancer subtypes do not only differ molecularly but also have different morphological and therapeutic targets. 2,3
Biomarkers have an important role in lung cancer. About two-thirds of NSCLC patients are often late to be diagnosed earlier because they already have metastasis, especially in stage III or IV and at these stages the treatment options are limited causing the prognosis worse and the patient’s survival rate low. For this reason, there is a strong clinical need that has not yet been met for biomarkers in lung cancer, especially for new biomarkers that can help in establishing early diagnoses so as to improve prognostics and predict responses to various therapies.4 The biomarkers in lung cancer are based on the results of the type of lung cancer histology found.
Definition Of Biomarkers
Biomarkers have not yet had a universal definition, but biomarkers are understood as biomolecules that arise as a result of physiological or pathological processes. A biomarker that is considered as ideal is one that cannot be detected or has a low value in a non-inflammatory condition and it will increase in an inflammatory condition which will further decrease when the inflammatory process subsides.5
According to Nicollas et al, biomarker is defined as a substance or activity that can be measured and evaluated objectively as an indicator for normal or abnormal biological processes in an organism by analyzing biomolecules such as DNA, RNA, proteins, peptides, and chemical modification of biomolecules. However, it must be recognized that the definition of biomarkers has evolved over the past decade, bringing the definitions based on WHO that the biomarkers are substances, structures or processes that can be measured in the body or product and affect or predict the result or disease. The biomarkers of cancer are present in tumor or serum tissue and cover a wide variety of molecules, including DNA, mRNA, enzymes, metabolites, transcription factors, and cell surface receptors.3
Classification Of Biomarkers
Biomarkers can be classified into four types namely diagnostic, prognostic, predictive and therapeutic:
1. Diagnostic biomarker allows early detection of cancer by non-invasive way and as a secondary prevention of cancer. This biomarker can distinguish a disease with other diseases or normal condition. Examples: CYFRA 21-1 (Cytokeratin), ProGRP (Pro-Gastrin Release Peptide) are used for screening various malignancies including lung cancer. 4,5
2. Prognostic Biomarker provides information on monitoring and progress of the anti-cancer therapy, assessment of the disease, rate of development (clinical or biological characteristics) regardless the treatment and prognosis of the remission toward the disease. For example CEA which is biomarkers in all types of lung cancer whose concentration level increases in the blood. Tumors with high CEA expression have high metastatic potential which probably be caused by the adhesion of cells between the tumor and blood vessels. 5,6
3. Predictive Biomarker indicates whether or not certain treatments may provide clinical benefits for patients or can predict the response of therapy to targeted patients and define subpopulations of patients who are likely to benefit from certain therapies. Examples: EGFR, KRAS, BRAF, PDGFRA, KIT, HER2, BCR-ABL, and EML4-ALK. 6,7
4. Therapeutic Biomarker.
Therapeutic biomarker is generally protein that can be used as therapeutic target. Example:
tyrosine kinase inhibitors (TKIs) and monoclonal antibodies in NSCLC patients. 6,7
Based on the clinical application, biomarkers are divided into three namely serological biomarker, molecular biomarker and imaging biomarker. The serological biomarker can be found in body fluids (extracellular) and tumor cells/tissues of cancer patients and generally are proteins (antigens). The method used to measure the level of tumor marker serologically uses the ELISA (enzyme-linked immunosorbent assay) method with the patient’s blood material (serum). 6 While the molecular biomarker analyzes DNA, all RNA molecules, changes in protein interactions and immunological responses. The imaging biomarker also has advantages in detecting early diseases in addition to molecular biomarker. The imaging biomarker is non-invasive. Some biomarkers which are image-based namely X-Ray, Computed Tomography (CT), Positron Emission Tomography (PET), Single Photo Emission Computed Tomography (SPECT) and Magnetic Resonance Imaging (MRI).8,9,10
Biomarkers In Lung Cancer Based On The Histology
The lung cancer by its histological type is divided into two groups namely Small Cell Lung Carcinoma (SCLC) and Non-Small Cell Lung Carcinoma (NSCLC). NSCLC has various molecular features besides adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, namely adenosquamous carcinoma and large cell neuroendocrine carcinoma Adenocarcinoma originates from bronchial mucosal gland cells and this histological subtype is the dominant among other types of lung cancer. Squamous carcinoma originates from bronchial epithelial cells characterized by specific differentiation such as keratinization, keratin formation, or the presence of intercellular bridges. Аdenosquamous carcinoma is a type of cancer that contains two types of cells that contain adenocarcinoma components and squamous cell carcinomas (thin and flat cells, lining or coating certain organs and gland-like cells). Large cell carcinoma is malignant neoplasms that are not differentiated and are categorized as NSCLC subtypes derived from lung epithelial cells, while large cell neuroendocrine carcinoma is a malignant epithelial tumor consisting of large polygon cells that are not histologically clearly differentiated. (Figure 1).11
Figure 1. Classification based on WHO on histological lung cancer types.11
Carcinogenesis Process As Biomarkers Origin
The process of growth from normal cells into malignant cancer cells is called carcinogenesis. This process is usually caused by genetic instability that occurs between the oncogene group and the suppressor gene group. Oncogenes are the genes that encode
“information” of malignancies, while the suppressor genes or anti-oncogenic genes are genes that suppress the growth toward malignancy. The various mutations in the two proto oncogenic regions in normal cells can cause proto oncogenes to turn into oncogenes so that normal cells can turn into cancer cells. 12
The process of carcinogenesis is not only influenced by genetic changes but also influenced by epigenetic processes. Epigenetics are the phenotypic changes that do not involve genetic abnormalities, especially in DNA nucleotides. Epigenetic changes can be defined as order of gene expression through changes in the structure of chromatin without changing DNA sequences. DNA mutations are irreversible whereas epigenetic changes are reversible. 12
Chemicals, viruses and radiation are substances that can be carcinogenic. This carcinogen can cause mutations and these changes can become malignant due to the failure in the DNA- Repair process. If gene damage cannot be repaired, mutants can form. Mutants are genes that undergo nucleotide base sequence changes that occur due to addition, subtraction or movement of nucleotide bases. Mutations in these genes can cause abnormalities in the order, expression and deviation of protein-coding genes that affect cell vital functions such as cell proliferation and differentiation. The development of normal cells turning into cancer cells is a complex and gradual process that starts from initiation, promotion, progression, and metastasis. This process can be seen in the following figure 2. 12
Carcinoma CA
Small Cell CA 20-25%
Non Small Cell CA 75-80%
Adeno CA Adenosquamouss
CA
Large Cell CA
Squamous CA Large Cell
Neuroendocrine CA
Figure 2. Stages of Carsinogenesis 12
The initiation stage in carcinogenesis is characterized by genetic changes that cause normal cells to become cancer cells. The promotion stage is the development of tumor mass triggered by abnormal cells that survive and continue to split up, the growth becomes uncontrollable so that the size of the tumor becomes larger and cancer cells begin to spread to surrounding tissues or to other organs or metastasize.2 In the figure 3 shows that lung cancer cells occur genetic changes such as mutations, translocation, activation of oncogenes, inactivation in tumor suppression genes, and epigenetic changes through the involvement of receptors and in their domain. Furthermore, these receptors and domains can subsequently be used as molecular biomarkers. 2, 12
Serological biomarker has conventionally referred to substances, especially proteins, which are directly produced by malignant cells or produced by other cells, in response to certain malignant or other non-malignant conditions. This biomarker can be associated with malignancy in certain organs for example CYFRA 21-1 which is a cytokeratin-19 fragment dissolved in serum and known to be expressed in all body tissues, but its main expression is in the lung. 8
Figure 3. Molecular changes in lung cancer 2
SMALL CELL LUNG CANCER (SCLC) BIOMARKERS a. SCLC Molecular Biomarker
Recently the DLL3 protein has been studied as a potential biomarker that can be targeted for SCLC. This protein is usually expressed in the fetal brain where it suppresses oncogenesis and tumor growth. In 2015 Saunders et al found an association between this DLL3 expression and the neuroendocrine phenotype. The research that carried out on these human neoplastic tissues showed the order and deviant expression of DLL3 in SCLC. In SCLC tumors, the use of anti- DLL3 treatment produces effects in eradicating tumor trigger cells. Based on these results, several further studies and clinical trials investigated the role of DLL3 and the effectiveness of conjugated drug administration for target therapy in SCLC. Another known biomarker from SCLC is ProGRP (Pro-Gastrin Release Peptide). ProGRP is found in the blood plasma of SCLC patients and medullary thyroid cancer (> 200 pgmL-1). ProGRP in healthy person is 35 pgmL−1 and in patients with benign tumors is 45-103 pgmL−1. However, the use of this biomarker does not correlate with the stage of lung cancer. 13
b. SCLC Serology Biomarker
Serum biomarker has low sensitivity, specificity and reproducibility. Neuron-Specific Enolase (NSE) in SCLC has been investigated and reported to have a role in diagnosis, treatment and follow-up since the mid-eighties. NSE is a specific glycolytic polypeptide isoenzyme enolase that catalyzes the biosynthesis of dopamine produced by central and peripheral neurons and stimulation of malignant tumors. NSE is only specific to SCLC. The normal value of NSE is ≤15 ng/ml.13 The NSE level was found to have a stronger correlation with disease rates and response to treatment in patients compared with other markers. The level of NSE in SCLC patients is considered to have good specificity, while the sensitivity appears depending on the stage of the disease. The NSE measurements before therapy are also useful in evaluating response durations, as from multivariate analysis. On the other hand, according to Zhu et al CEA has a relevance of
Growth Factor Receptor
EGFR FGR-1
MET
Translocation
ALK ROS-1
RET
Oncogene Activation
K-RAS B-RAF DDR2 PIK3CA
Inactivation Of Tumor Supressor
Genes
P53 LKB-1
PTEN
Epigenic Chances
DNA Metilasyone
Histon Deasetiaz
miRNA
recently investigated as a predictor of brain metastasis and survival in SCLC prophylactic cranial irradiation patients.13
Hou et al found that CTCs (circulating tumor cells) after one cycle of chemotherapy were independent prognostic factors for SCLC. CTCs are cancer cells that are in blood vessels that originate from tumors and have the potential for the occurrence of metastatic processes. SCLC is the cancer with a higher level of CTCs. Given the potential metastasis of these cells, much research has been carried out to understand the diagnostic, prognostic and predictive value of neoplastic disease and their uses as biomarkers. The prognostic value of CTC in SCLC remained controversial until early 2000s mainly because the detection technology has not been well developed.13 Several other studies have recently confirmed the relationship between CTCs and poor prognosis in SCLC patients. But the role of CTCs as predictors of therapeutic responses is still quite debatable. Wang et al found an association between CTCs levels and NSE serum but not with the therapeutic response.13
Biomarkers For Nsclc
a. NSCLC Molecular Biomarker
The most common types of NSCLC include adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Other subtypes, including large cell neuroendocrine carcinoma represent a very small proportion of the total cases of NSCLC. Advances in molecular biology of lung cancer have led to the identification of a number of potential biomarkers that may be relevant in the clinical management of patients with NSCLC. 12,14
1. The Epidermal Growth Factor Receptor (EFGR) and the T790M Mutation
EGFR are two of the most important mutation drivers found at NSCLC. EGFR is over- expressed in 62% of NSCLC, and its expression has been associated with a poor prognosis.15 EGFR is a growth factor receptor expressed on the cell surface involved in cell growth and division after ligand binding which will lead to tumor development and growth.16 EGFR can have mutations, and one of the rare mutations is the T790M mutation in exon 20 or insertion in exon 20. This T790M mutation is related to resistance to the first generation of tyrosine kinase inhibitors (TKI).14,17
2. Anaplastic Kinase Lymphoma (ALK)
ALK is a member of receptor tyrosine kinase of the superfamily insulin receptor.16 EML4- ALK fusion has been detected in 3.7% to 7% of NSCLC, usually in adenocarcinomas and is more common in young patients who have never smoked. ALK fusion describes the population of patients with pulmonary adenocarcinoma that is very responsive (57% -74%) to crizotinib which is an ALK inhibitor. The patients who are treated with crizotinib showed significantly better response rates compared to patients who received chemotherapy. Several second-generation of ALK inhibitors targeting ALK-positive NSCLC, such as alectinib and ceritinib have been developed and are currently being evaluated in clinical trials.18,19
3. ROS1
ROS Proto-oncogenic 1 (ROS1) receptor tyrosine kinase is the receptor tyrosine kinase, a member of insulin receptor family and is located in the long arm of chromosome 6 at position 22. ROS1 plays a role in the differentiation of epithelial cells during the development of various organs. ROS1 was initially found in glioblastoma and has also been reported in
oncogenic. NSCLC with ROS1 usually occurs in young children, female, who have never smoked with a histological diagnosis of adenocarcinoma. Clinical trials have reported that patients with advanced NSCLC with ROS1 show a response rate of up to 80% with crizotinib treatment.13,18
4. Proto-oncogen RET
Proto-oncogenes RET are located in the long arm of chromosome 10 at position 11. RET was initially identified in papillary thyroid carcinoma. About 1% to 2% of NSCLC contains RET fusion. It generally occurs in adenocarcinomas with less differentiated solid formations in young patients who have never smoked. Invitro studies show that indeed RET fusion leads to the oncogenic transformation, which can be obstructed by vandetanib, sorafenib, and sunitinib.13
5. MET Proto-oncogen
The MET gene is located in the long arm of chromosome 7 at position 31. MET activates several signaling pathways that play a basic role in cell proliferation, survival, motility, and invasion. MET gene mutations were first reported in patients with papillary renal cell carcinoma. MET mutations were found 3% in SCLC and 8% in lung adenocarcinomas. In NSCLC, a high MET gene copy has been described as a poor prognosis.12 In cancer cases, it is often observed the association of MET with migration, invasion and angiogenesis. MET is currently an interesting therapeutic target in several cancer cases.13,20
6. The discoidin domain receptor tyrosine kinase 2 gene (DDR2)
DDR2 is a domain located in the long arm of chromosome 1 at position 23.3. DDR2 activates and promotes cell migration, proliferation, and viability. In cancer cases, DDR2 mutations have been reported in melanoma and cervical cancer, stomach, bladder, and colorectal. In lung cancer, DDR2 mutations occur in 3% to 4% of squamous cell lung carcinomas compared to 0.5% of adenocarcinomas that are active smokers.13
7. The Fibroblast Growth Factor Receptor (FGFR)
FGFR is located on chromosome 8 at position 12 and promotes cell viability, motility, invasive, and proliferation. The FGFR gene plays an important role in activating cancer, through the mechanism of FGFR gene amplification, somatic missense mutations, and translocation chromosomes. FGFR has been identified as an oncogenic booster in breast, stomach, endometrial, urothelial, and brain tumors. In lung cancer, the incidence of FGFR1 amplification is significantly higher in squamous cell carcinoma (20%) compared to adenocarcinoma (3%) and is more frequent in active smokers compared to those who have stop smoking or even those who have never smoked.13,20
8. The Human Epidermal Growth Factor Receptor 2 Gene (HER)
HER2 (ERBB2) is a proto oncogen located on chromosome 17 at position 12, and encodes the receptor tyrosine kinase, member of ERBB receptor family. HER2 expression or its amplification is found in many cancers including breast and gastric cancer. This mutation is found more often in adenocarcinomas especially in women, asian races, nonsmokers or light smokers. Different studies strengthen the importance of lung adenocarcinoma screening for HER2 mutations as a method for selecting patients who can benefit from targeted HER2 therapies namely afatinib and trastuzumab, which have shown a response rate of around 50%.13
9. The B-RAF proto-oncogene, serine/threonine kinase (BRAF)
BRAF is located in the long arm of chromosome 7 at position 34. When activated by oncogenic mutations, BRAF promotes cell growth, proliferation, and viability. BRAF mutations have also been reported in 1% to 3% of NSCLC. NSCLCs with BRAF mutations have been reported to be mostly adenocarcinomas. Patients with BRAF mutations are mostly current or ex-smokers. Nevertheless, patients with NSCLC and BRAF mutations have a worse prognosis and a lower response to chemotherapy. BRAF inhibitors, such as vemurafenib and dabrafenib, have selective activity against mutant-V600E of BRAF kinases, with an overall response rate of 33% to 42%. BRAF inhibitors are now tested for NSCLC, such as trametinib, selumetinib, and dasatinib, and are currently under evaluation in clinical trials.10,13,18
10. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)
PI3K is a regulator and part of several pathways involved in cell growth, transformation, adhesion, apoptosis, viability, and motility. The PIK3CA gene is located in the long arm of chromosome 3 at position 26.3. PKI3CA amplification and mutation have been reported in many tumors including lung cancer. In fact, mutations were found in 4% of patients with NSCLC. This mutation was reported more frequently in squamous cell lung carcinoma compared with adenocarcinoma (6.5% vs. 1.5%). 13
b. NSCLC Serology Biomarker
The higher neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have shown a significant relation with the poor survival of patients with NSCLC.18 In addition, previous studies in NSCLC patients have shown that changes in CEA or CYFRA21 levels -1 during chemotherapy and radiochemotherapy. CEA or CYFRA21-1 has a higher predictive value and can be used in treatment monitoring. 18,21
Specifik Biomarker Squamous Cell Carcinoma
Squamous cell carcinoma originates from bronchial epithelial cells. One characteristic feature of squamous lung cancer is high CK-19 (cytokeratin-19) and CYFRA 21-1 (cytokeratin fragment-19). CK-19 is a protein component of epithelial cells. CYFRA 21-1 increases during the process of malignancy of normal epithelial cells. Lee et al found that CYFRA 21-1 biomarkers increased in squamous cell carcinoma. Other important reports by Lai et al are that the sensitivity of CYFRA 21-1 for squamous cell carcinoma, adenocarcinoma and large cell carcinoma are 62%, 39%, and 36%, respectively. Therefore, it shows that the serum level of CYFRA 21-1 in squamous cell carcinoma is significantly higher than other types of cancer cells.22,23 Another specific protein biomarker for squamous cell lung cancer is SCCA (Serum Squamosa Cell Carcinoma Antigen) which is a 48-kDa protein found in squamous cell lung cancer. SCCA is a serine-like protease inhibitor that inhibits tumor cell apoptosis, stimulates invasion and metastasis. In addition there is FGFR (Fibroblast Growth Factor Receptor) and Discoidin Domain Reseptor‐2 (DDR2) biomarkers are seen in squamous cell carcinomas.23
Specifik Biomarker Adenocarcinoma
Adenocarcinoma originates from bronchial mucous gland cells. The diagnosis of adenocarcinoma is identified by mutational molecular biomarkers, namely EGFR (Epidermal Growth Factor Receptor), ERCC (Extracellular RNA Communication Program), BRAF (B-Raf Proto Oncogene), RRM 1 (Ribonucleoside Diphosphate Reductase), KRAS (KRAS Proto Oncogene), BRAF (B-Raf Proto Oncogene), RRM 1 (Ribonucleoside Difosfat Reductase), KRAS (KRAS Proto Oncogenes) RET (Proto-oncogene tyrosine-protein kinase receptor Ret), TS (Thymidylate Synthetase), ROS-1 (Reactive oxygen species-1), and EML4-ALK (Echinoderm Microtubule Associated Protein-Like 4). 2,25
Micro RNA (miRNA) is a small RNA molecule encoded by the microRNA gene. In a recent meta-analysis study, high miR-21 expression was associated with low survival in NSCLC.
It was reported that miR205 was specific for squamous cell carcinoma, whereas miR-124a was reported specifically for adenocarcinoma. 2,25
The serological biomarker found significant values of CEA and CYFRA 21-1 in lung adenocarcinoma shown by Ando et al, the increase of these two markers correlated with the advanced stage of the disease. Several reports have shown that CEA levels are significantly higher in patients with adenocarcinoma compared to patients with squamous cell carcinoma. The normal CEA value is ≤5.2 ng / ml, although there are 3% of people with CEA 5.2-7.5 ng/ ml.
Whereas CYFRA has a normal reference ≤ 3.3 ng / ml.23
Specifik Biomarker Large Cell Carcinoma
Large cell carcinoma is a malignant epithelial tumor consisting of large cells that are not differentiated and histologically polymorphic. Data on specific biomarkers of this type of cancer have not been found. 26,27
Table 1. The frequency of major molecular changes in adenocarcinomas and squamous cell carcinomas.13,24
Gene Alteration Adenocarcinoma Squamos Cell Carcinoma Frequency
EGFR Mutation 10% 3%
ALK Rearrangement 4-7% None
ROS Rearrangement 1-2% None
KRAS Mutation 25-35% 5%
MET Mutation 8% 3%
FGFR Amplification 3% 20%
HER2 Mutation 1,6-4% None
BRAF Mutation 1-3% 0,3%
PIK3CA Mutation 2% 7%
RET Rearrangement 1-2% None
DDR2 Mutation 0,5% 3-4%
Specifik Biomarker Large Cell Neuroendocrine Carcinoma
Large cell neuroendocrine carcinoma (LCNEC) is very rare and difficult to diagnose, often mimicking conventional non-small cell lung cancer (NSCLC) both clinically and morphologically. Commonly known biomarkers are TOP SST (Topoisomerasis Somatostatin Precursor) and ERCC1 (Excision Repair 1, Endonuclease Non-Catalytic Subunits). Some gene expressions and biomarker functional expressions in other LCNECs are CEACAM, vitamin-D binding protein and CD44. Thyroid transcription factor-1 (TTF-1) is also mentioned as a marker to distinguish LCNEC and not LCNEC. 26,27
Summary
Lung cancer is classified into two groups, namely Small Cell Lung Cancer (SCLC) and Non- Small Cell Lung Carsinoma (NSCLC). These lung cancer subtypes not only differ morphologically but also have different molecular bases and have different therapeutic targets.
Biomarkers are characteristics that can be measured and give an indication of the patient’s biological condition or the tumor. An ideal biomarker must be inexpensive, easily obtained and with minimal invasive techniques. Currently diagnostic and prognostic biomarkers can help improve management in lung cancer patients. The use of the most specific biomarkers will help improve the early diagnosis of lung cancer and can distinguish between the types of histological lung cancer.
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