Clinical Implications of Early Molecular Diagnosis in Lung Cancer- brief review

Lung cancer is a major issue in oncology pathology worldwide. According to the WHO, this disease is the number one cause of death in both men and women worldwide [1]. Worldwide The countries with the highest incidence of lung cancer meet in Polynesia and Hungary [2]. in Europe in 2018 According to the data provided by GLOBOCAN, the incidence of lung cancer was 470,039 new cases, of which 311,843 men and 158 196 women [3]. The highest incidence was in Hungary, Austria, Germany, Slovenia, Latvia, Romania, the last places being Portugal, Malta, Lichtenstein [4]. For the correct analysis of the survival rate of patients diagnosed with lung cancer, the tumor stage (microcellular lung cancer and non-microcellular lung cancer) were considered; histopathological type (adenocarcinoma, squamous cell carcinoma, neuroendocrine lung tumors small cell carcinoma, carcinoid; type of treatment (surgical, surgery-chemotherapy, surgery-radiotherapy, surgery-chemo-radiotherapy) [5]. Advanced lung cancer has an extremely poor prognosis, with a 5-year survival of only 5% [6]. An early diagnosis of lung cancer is needed to increase survival. A rapid personalized diagnosis (molecular, imaging, anatomopathological, immunohistochemical) is required in order to initiate an early personalized treatment [7]. After establishing the personalized diagnosis, the therapeutic attitude in the case of lung cancer the treatment can be started [8]. In this context, Molecular diagnosis of lung cancer can be made in the early stages of the disease.


Introduction
Lung cancer is a major issue in oncology pathology worldwide. According to the WHO, this disease is the number one cause of death in both men and women worldwide [1].
Worldwide The countries with the highest incidence of lung cancer meet in Polynesia and Hungary [2]. in Europe in 2018 According to the data provided by GLOBOCAN, the incidence of lung cancer was 470,039 new cases, of which 311,843 men and 158 196 women [3]. The highest incidence was in Hungary, Austria, Germany, Slovenia, Latvia, Romania, the last places being Portugal, Malta, Lichtenstein [4]. For the correct analysis of the survival rate of patients diagnosed with lung cancer, the tumor stage (microcellular lung cancer and non-microcellular lung cancer) were considered; histopathological type (adenocarcinoma, squamous cell carcinoma, neuroendocrine lung tumors -small cell carcinoma, carcinoid; type of treatment (surgical, surgery-chemotherapy, surgery-radiotherapy, surgery-chemo-radiotherapy) [5]. Advanced lung cancer has an extremely poor prognosis, with a 5-year survival of only 5% [6]. An early diagnosis of lung cancer is needed to increase survival. A rapid personalized diagnosis (molecular, imaging, anatomopathological, immunohistochemical) is required in order to initiate an early personalized treatment [7]. After establishing the personalized diagnosis, the therapeutic attitude in the case of lung cancer the treatment can be started [8]. In this context, Molecular diagnosis of lung cancer can be made in the early stages of the disease. CEA is not a specifi c tumor marker for lung cancer, but together with other markers it can provide informations. There has been a higher increase in serum levels in Non-small cell lung cancer (NSCLC) [10,15]. Normal EAA values are 3.8 ng / ml [10].
The mutation of the TP53 tumor suppressor gene occurs in Non-small cell lung cancer in 34% of smokers patients with NSCLC [16]. The presence of this protein suggests resistance to chemotherapy [17]. TP53 detection is realised by FISH technique [18].
CYFRA 21-1 in the literature of speciality is specified to be the highest values together with levels of CEA with serum squamous cell carcinoma (SCCA) which characterizes the squamous lung cancer [19].
SCCA -squamous cell carcinoma-associated antigen -is protease serum inhibitors, is associated with the emergence and development of squamous cell carcinoma. It has very high values and is closely related to the prognosis of squamous lung cancer. [20]. The presence of the SCCA marker at the onset of the disease may suggest the diagnosis [21].
Thioredoxin (Trx) -is a protein that is very important in the redox process related to the lung tumor, in the peripheral blood under oxidative stress conditions [22]. The presence of this marker is interpreted alongside of SCCA, CYFRA21-1 and CEA [19]. NSE-Neuron-specific enolasis -is the tumor marker representative of long cell carcinoma (SLC). Its values have a strong correlation between the increased percentage of NSE and the stage of the disease [23].
Thioredoxin (Trx) -Has the highest values in small cell lung carcinoma in peripheral blood [19].
Chromogranin A (CHGA) -It is a marker specific to neuroendocrine tumors, which exhibit elevated levels in small cell lung cancer [24]. Synaptophysin (SYP) is a tumor marker specific to neuroendocrine tumors [24].
Peptide that releases gastrin (ProGRP) -It is a neuropeptide that occurs in neuroendocrine cells outside the stomach, being specific to neuroendocrine tumors [25]. Normal values for an adult are <60 ng/L, with a higher concentration in smokers [23].
In patients with small cell lung carcinoma this marker has very high values.
Serum ferritin is an iron storage protein that occurs in serum and some biological fl uids of the body [26]. Although the mechanism of occurrence of very high levels is not known, in small cell lung carcinoma (SCLC) and metastatic cancers we experience very high levels of serum ferritin [27]. The average survival time of patients with low serum ferritin was found to be longer than that of high levels [26].

Profi le of typical/atypical carcinoid tumor serum: chromogranin A (CgA), neuron-specifi c enolase (NSE), Urinary into 5-hydroxyindoleacetic acid (5-HIAA)
Chromogranin A (CHGA) -It is the most sensitive and convenient marker of neuroendocrine tumors, especially for bronchopulmonary carcinoid tumors [28]. It is an amino acid glycoprotein secreted by neuroendocrine cells [29]. The increased level predicts a generally poor prognosis of survival.
It is a tumor marker used for monitoring therapeutic effi ciency [30].
Neuron-specifi c enolase (NSE) -is an enzyme expressed by cells of neural origin and weakly different cells, refl ecting the presence of high-grade disease and the increases refl ect a high aggressiveness of the tumor [28]. It is a marker with elevated values in bronchopulmonary carcinoid but is not specifi c to this disease [31].
Urinary and plasma 5-hydroxyindoleacetic acid (5-HIAA) -It is a metabolite of serotonin that is excreted in the urine in tumors that secrete serotonin [28]. It was one of the fi rst markers used to diagnose neuroendocrine tumourspulmonary carcinoid and to monitor treatment response [32].
Plasma 5-HIAA measurement has been shown to correlate well with 5-HIAA urinary, and blood sampling is preferred by patients than in 24-hour urine collections [33,34].
Urinary serotonin and plasma -is a biogenic amine synthesized from the essential amino acid tryptophan [35].
Normally a small amount is found in the plasma [35]. Serotonin is detected in increased amounts in blood and urine tests [33].