Significance of KRAS and BRAF mutation testing in colorectal cancer patients

Uvod. Učestalost i smrtnost od karcinoma debelog crijeva u stalnom je porastu i zato je ova bolest vodeći zdravstveni problem u svijetu i u Hrvatskoj. Nastaje složenim procesom tijekom kojeg dolazi do uzastopnih promjena u tumor supresorskim genima, onkogenima i genima za popravak krivo sparenih baza. Karcinom debelog crijeva može se pojaviti sporadično ili kao nasljedni oblik; u oba slučaja radi se o vrlo heterogenoj skupini zloćudnih tumora. Geni KRAS i BRAF spadaju u skupinu onkogena. Njihovi produkti posreduju u prijenosu signala od receptora za epidermalni čimbenik rasta (EGFR) na unutarstanične mitogenom aktivirane protein kinaze (MAPK), te na taj način sudjeluju u kontroli staničnog ciklusa. Najčešće promjene ovih gena su točkaste mutacije. Događaju se u dobroćudnoj fazi nastanka karcinoma debelog i završnog crijeva i odgovorne su za klinički značajan rast tumora. Cilj ovog rada je odrediti učestalost i vrstu mutacija gena KRAS i BRAF u uzorcima karcinoma debelog i završnog crijeva te ispitati da li postoji povezanost mutacija s patohistološkim pokazateljima lošije prognoze bolesti. Materijali i metode. U istraživanje je uključeno 113 arhivskih uzoraka (tkiva fiksirana u formalinu i uklopljena u parafin) karcinoma debelog i završnog crijeva osoba koje boluju od te bolesti, operiranih u razdoblju od 2009. do 2011. godine u KBC-u Zagreb. Za izdvajanje DNA korišteno je 6-10 rezova debljine 10 mikrometara svakog pojedinog tkiva. Sedam najčešćih točkastih mutacija gena KRAS (p.G12A, p.G12D, p.G12V, p.G12R, p.G12C, p.G12S, p.G13D) određeno je metodom kvantitativnog PCR u stvarnom vremenu, a jedna mutacija gena BRAF (p.V600E) metodom PCR u stvarnom vremenu uz analizu krivulje taljenja. Za svakog bolesnika prikupljeni su podaci o dobi, spolu, veličini tumora, histološkom gradusu tumora, stadiju po Dukes'u, angioinvaziji i smještaju tumora. Usporedba učestalosti mutacija u uzorcima podijeljenim po skupinama učinjena je Fisherovim testom, statističkom obradom podataka u programu MedCalc v9.3.2.0. Rezultati. Mutacije gena KRAS dokazane su u 39,8% uzoraka, a najčešće je dokazana mutacija p.G12V (42,2% uzoraka). Tranzicije i transverzije bile su podjednako zastupljene. Mutacija p.V600E gena BRAF dokazana je u 8,8% uzoraka i to isključivo u uzorcima s nemutiranim genom KRAS. Učestalost mutacija gena BRAF bila je viša u loše diferenciranim tumorima i tumorima klasificiranim u stadij bolesti Dukes'C (p = 0,04). Sve mutacije gena BRAF dokazane su u karcinomima debelog crijeva (p = 0,01). Zaključak. Učestalost mutacija gena KRAS i BRAF u populaciji bolesnika s karcinomom debelog i završnog crijeva iz Hrvatske nalazi se unutar granica prijavljene učestalosti istih mutacija u drugim populacijama svijeta. Ističe se visok udio mutacije p.G12V koja se povezuje s najlošijom prognozom bolesti, što bi se moglo povezati s kontinuirano visokom smrtnošću od ove bolesti u Hrvatskoj. Viša učestalost mutacija gena BRAF u tumorima lošije prognoze upućuje na njihovu ulogu u napredovanju bolesti.Introduction. Incidence and mortality of colorectal cancer are on constant increase and represent one of the major health problems in the world as well as in Croatia. The development of colon cancer is a multistep process which involves successive genetic alterations of tumor supressor genes, oncogenes and mismatch repair genes. Colon cancer can arise as sporadic or familial hereditary colon cancer, representing in both cases a very heterogeneous group of malignant tumors. KRAS and BRAF genes are oncogenes. Their products mediate and control cellular responses through mitogen activating protein kinase signal pathway (MAPK), downstream of epidermal growth factor receptor (EGFR). The most common activating mutations of these oncogenes are point mutations. They arise early during the development of colorectal cancer and are associated with the clinically significant tumor growth. The aim of this study was to determine the incidence of KRAS and BRAF gene mutations in colorectal cancer patients in Croatia and to assess whether they are linked with clinicopathological features of poor prognosis. Materials and methods. A total of 113 consecutive colorectal cancer patients were included in this research. They were operated on 2009-2011 period at University Hospital Center Zagreb. Resected tumor samples were formalin fixed and paraffin embedded and prepared for DNA extraction as four to six 10-μm sections. Seven common point mutations of KRAS gene (p.G12A, p.G12D, p.G12V, p.G12R, p.G12C, p.G12S, p.G13D) were identified using quantitative real-time PCR, and the most common mutation of BRAF gene (p.V600E) was detected using real-time PCR by fluorescence melting curve analysis. Clinical and pathological data such as age, sex, tumor size, histologic grade, Dukes’stage, angioinvasion and tumor position were collected for each patient. Differences in clinical and pathological variables between the groups of patients with and without BRAF and KRAS mutations were analyzed using Fisher exact tests performed using MedCalc v9.3.2.0. Results. KRAS gene mutations were detected in 39.8% samples, and the most frequent mutation was p.G12V detected in 42.2% positive samples. Transitions and transversions were equally present. BRAF gene mutation p.V600E was detected in 8.8% samples, exclusively in tumors without KRAS mutations. Incidence of BRAF gene mutation was higher in poor differentiated and Dukes'C tumors (p = 0.04). All BRAF gene mutations were detected in colon cancers (p = 0.01). Conclusion. The incidence of KRAS and BRAF gene mutations in colorectal cancer patients from Croatia is within commonly accepted limits. High percentage of p.G12V aggressive mutation can be related to high mortality from colorectal cancer in Croatia. High incidence of BRAF gene mutations in tumors with poor prognostic markers shows that BRAF mutations play a role in the progression of this disease

UTJECAJ KORIŠTENJA SREDSTAVA IZ EU FONDOVA NA RAZVOJ RURALNOG TURIZMA NA PODRUČJU SPLITSKO – DALMATINSKE ŽUPANIJE : Diplomski rad

Tema ovog diplomskog rada je utjecaj korištenja sredstava iz EU fondova na razvoj ruralnog turizma Splitsko-dalmatinske županije. Rad prezentira teorijske spoznaje usko vezane za temu rada, a to se odnosi na definiranje sredstava iz EU fondova (IPARD i EAFRD program) koji su namijenjeni ruralnom turizmu, kao i definiranje ruralnog turizma općenito. IPARD je pretpristupni program pomoći, za razdoblje 2007.-2013. g.,a EAFRD je novi program pomoći, za razdoblje 2014.-2020. g. Uz ove programe Europske pomoći, postoje i državne potpore uz pomoć kojih država pomaže poduzetnicima. Turizam se u Republici Hrvatskoj počeo razvijati 80-ih godina prošlog stoljeća ali tijekom Domovinskog rata sve je uništeno. Bilo je potrebno određeno vrijeme da se turizam ponovo razvije i dosegne dobru razinu. U njegovom razvoju EU programi pomoći su uvelike pomogli. Sada se turizam dijeli na više vrsta i oblika. U ovom radu detaljno je analiziran ruralni turizam koji se također može podijeliti na nekoliko oblika. Nadalje, putem anketnog istraživanja provedenog u svrhu pisanja rada, dolazi se do zaključaka vezanih za utjecaj korištenja sredstava iz EU fondova na razvoj ruralnog turizma. Provedena su dva anketna upitnika. Jedan anketni upitnik odnosi se na korisnike mjera a drugi na djelatnike koji su izravno ili neizravno uključeni u turizam u svrhu utvrđivanja njihovih stavova i percepcija. Nakon teorijskog i empirijskog dijela, napisan je zaključak koji obuhvaća cijeli rad.The topic of this graduate thesis is the influence of the using resources from EU funds for the development of rural tourism in the Split-Dalmatia County. The paper presents theoretical notions closely related to the topic of work, relating to the definition of resources from EU funds (IPARD and EAFRD program) for rural tourism, as well as the definition of rural tourism in general. IPARD is a pre-accession assistance program for the period of 2007-2013. The EAFRD is a new aid program for the period of 2014-2020. In addition to these European aid programs, there are state aids with the help of which the state helps entepreneurs. Tourism in the Republic of Croatia began to develop in the 80s of the last century, but during Homeland War, everything was destroyed. It took a while for tourism to re-develop and reach a good level. In its development, EU programs have helped greatly. Tourism is now divided into several types and shapes. In this paper, rural tourism has been analyzed in detail, which can also be divided into several forms. Furthermore, through a survey conducted for the purpose of writing the paper, there is a conclusion regarding the impact of the use of resources from EU funds on the development of rural tourism. Two questionnaire were conducted. One survey questionnare has been sent to users of measures and other to employees directly or indirectly involved in tourism in order to determine their attitudes and perceptions. After the theoretical and empirial part, a conclusion has been written that covers the whole work

UTJECAJ KORIŠTENJA SREDSTAVA IZ EU FONDOVA NA RAZVOJ RURALNOG TURIZMA NA PODRUČJU SPLITSKO – DALMATINSKE ŽUPANIJE : Diplomski rad

Tema ovog diplomskog rada je utjecaj korištenja sredstava iz EU fondova na razvoj ruralnog turizma Splitsko-dalmatinske županije. Rad prezentira teorijske spoznaje usko vezane za temu rada, a to se odnosi na definiranje sredstava iz EU fondova (IPARD i EAFRD program) koji su namijenjeni ruralnom turizmu, kao i definiranje ruralnog turizma općenito. IPARD je pretpristupni program pomoći, za razdoblje 2007.-2013. g.,a EAFRD je novi program pomoći, za razdoblje 2014.-2020. g. Uz ove programe Europske pomoći, postoje i državne potpore uz pomoć kojih država pomaže poduzetnicima. Turizam se u Republici Hrvatskoj počeo razvijati 80-ih godina prošlog stoljeća ali tijekom Domovinskog rata sve je uništeno. Bilo je potrebno određeno vrijeme da se turizam ponovo razvije i dosegne dobru razinu. U njegovom razvoju EU programi pomoći su uvelike pomogli. Sada se turizam dijeli na više vrsta i oblika. U ovom radu detaljno je analiziran ruralni turizam koji se također može podijeliti na nekoliko oblika. Nadalje, putem anketnog istraživanja provedenog u svrhu pisanja rada, dolazi se do zaključaka vezanih za utjecaj korištenja sredstava iz EU fondova na razvoj ruralnog turizma. Provedena su dva anketna upitnika. Jedan anketni upitnik odnosi se na korisnike mjera a drugi na djelatnike koji su izravno ili neizravno uključeni u turizam u svrhu utvrđivanja njihovih stavova i percepcija. Nakon teorijskog i empirijskog dijela, napisan je zaključak koji obuhvaća cijeli rad.The topic of this graduate thesis is the influence of the using resources from EU funds for the development of rural tourism in the Split-Dalmatia County. The paper presents theoretical notions closely related to the topic of work, relating to the definition of resources from EU funds (IPARD and EAFRD program) for rural tourism, as well as the definition of rural tourism in general. IPARD is a pre-accession assistance program for the period of 2007-2013. The EAFRD is a new aid program for the period of 2014-2020. In addition to these European aid programs, there are state aids with the help of which the state helps entepreneurs. Tourism in the Republic of Croatia began to develop in the 80s of the last century, but during Homeland War, everything was destroyed. It took a while for tourism to re-develop and reach a good level. In its development, EU programs have helped greatly. Tourism is now divided into several types and shapes. In this paper, rural tourism has been analyzed in detail, which can also be divided into several forms. Furthermore, through a survey conducted for the purpose of writing the paper, there is a conclusion regarding the impact of the use of resources from EU funds on the development of rural tourism. Two questionnaire were conducted. One survey questionnare has been sent to users of measures and other to employees directly or indirectly involved in tourism in order to determine their attitudes and perceptions. After the theoretical and empirial part, a conclusion has been written that covers the whole work

Effect of different pre-analytical conditions on plasma lactate concentration

Introduction: Plasma lactate is a frequently used and important parameter for medical decision making. To setup a pre-analytical algorithm, we aimed to investigate the influence of different test tube additives, aliquoting, ice storage and haemolysis on plasma lactate concentrations for possible sparing critically ill (ICU) patients of additional blood drawing. Materials and methods: In our study (N = 177), lactate concentration and haemolysis index (HI) were measured in aliquoted (AHP) and unaliquoted (HP) Li-heparin, NaF/K3EDTA and NaF/KOX plasma, centrifuged within 15 minutes after venipuncture, on Cobas c501 analyzer. Differences were tested using the Wilcoxon’s test and Passing-Bablok regression. Clinical accuracy of results was assessed in 107 ICU patients based on reference interval and clinical decision limits. Results: Lactate concentrations did not differ in NaF/K3EDTA and NaF/KOX plasma (P = 0.855). No clinically significant difference of AHP compared to NaF/K3EDTA lactate was found (y = 0.13 (0.08 to 0.19) + 1.02 (0.99 to 1.08) x) if samples were aliquoted within 30 minutes after venipuncture. On contrary, lactate concentrations in HP showed significant proportional difference (y = 0.07 (- 0.12 to 1.24) + 1.37 (1.22 to 1.56) x) and were clinically incorrect in 14% of patients. Transport in ice bath increases HI in NaF/K3EDTA (P < 0.001), but without influencing lactate results compared to room temperature (y = 0.03 (- 0.06 to 1.00) + 1.05 (0.99 to 1.11) x). Conclusions: Lactate determination in HP is unacceptable because of high proportional error and high risk of clinical inaccuracy compared to NaF/ K3EDTA. If pre-analytical conditions are met, AHP, NaF/K3EDTA and NaF/KOX plasma can be used interchangeably. Aliquoted Li-heparin samples alow measurement of other biochemical tests from a single tube and can spare ICU patients from additional blood drawing. Storage in ice bath provides no additional stabilization in NaF/K3EDTA tubes

THE ROLE OF KRAS GENE MUTATION TESTING IN COLORECTAL CANCER – A PREDICTIVE BIOMARKER OF RESPONSE TO EGFR INHIBITORS THERAPY

Aktivacija onkogena KRAS značajna je u kolorektalnoj karcinogenezi, a prisutnost KRAS-mutacije može se dokazati u više od 30% uzoraka kolorektalnog karcinoma (CRC). Među novijim lijekovima za liječenje metastatskog CRC-a jesu i pripravci koji sadržavaju protutijela na receptor za epidermalni čimbenik rasta (EGFR), cetuksimab i panitumumab. Nedavna istraživanja pokazuju da bolesnici s metastatskim CRC-om s mutacijama gena KRAS na 12. i 13. kodonu nemaju koristi od terapije inhibitorima EGFR-a. S ciljem određivanja statusa gena KRAS kao prediktivnog biomarkera testirana su 44 uzorka CRC-a na sedam poznatih mutacija gena KRAS. Nakon izdvajanja DNA iz tumorskog tkiva uklopljenog u parafinske blokove, prisutnost KRAS-mutacija određena je metodom PCR u stvarnom vremenu postupkom apsolutne kvantifikacije prvi put u Hrvatskoj, međunarodno certificiranom metodom. Mutacije su dokazane u 12 uzoraka tumora: pet bolesnika imalo je mutaciju Gly12Val (GGT>GTT), tri bolesnika Gly12Asp (GGT>GAT), dva bolesnika Gly13Asp (GGC>GAC) te po jedan bolesnik mutaciju Gly12Ser (GGT>AGT) i Gly12Cys (GGT>TGT). Naši nalazi pokazuju da je incidencija KRAS-mutacije u uzorcima bolesnika oboljelih od CRC-a 27%, što je podudarno s do sada objavljenim rezultatima u svijetu. Testiranje na KRAS-mutaciju prije primjene imunoterapije inhibitorima EGFR-a jedini je ispravni put u liječenju bolesnika s metastatskim CRC-om čime se poboljšava klinički ishod bolesti, a izbjegavaju se nepotrebne toksičnosti lijeka, nuspojave i financijski troškovi.Activation of KRAS oncogene has been implicated in colorectal carcinogenesis. KRAS mutations can be detected in more than 30% of all patients with colorectal cancer (CRC). Most recently, regimens that include anti-epidermal growth factor receptor (EGFR) targeted antibodies, cetuximab and panitumumab, for metastatic CRC have been developed. Several recent studies have shown that patients with KRAS mutations in codons 12 and 13 in metastatic CRC do not benefit from anti-EGFR therapy. With the aim to determine KRAS status as predictive biomarker, 7 known mutations of KRAS gene in codons 12 or 13 on 44 CRC samples were tested. After DNA extraction from paraffin-embedded tumor tissue blocks, KRAS mutations were analysed using quantitative real-time PCR with internationally certified method, for the first time in Croatia. Mutations were detected in 12 tumor samples: five patients with Gly12Val (GGT>GTT), three with Gly12Asp (GGT>GAT), two patients with Gly13Asp (GGC>GAC), one patient with Gly12Ser (GGT>AGT) and one with Gly12Cys (GGT>TGT) mutation in tumor. Our data about KRAS mutational status in the sample of Croatian population diagnosed with CRC have shown that incidence of KRAS mutation is 27%, which is consistent with results already reported worldwide. The final result must be a proper selection of the correct therapy with EGFR inhibitors for the patients with CRC which is critical for improving clinical outcomes, unnecessary toxicities, side effects and financial cost

Cystic Fibrosis – results of CFTR modulators in Croatia

Cistična fibroza najčešća je nasljedna bolest, koja skraćuje životni vijek, a uzrokuje je defekt u genu za transmembranski regulator provodljivosti cistične fibroze (eng. cystic fibrosis transmembrane regulator – CFTR). Poremećena je homeostaza elektrolita, što se očituje simptomima u više organskih sustava. Plućne manifestacije, s kroničnim infekcijama, upalom i, na kraju, respiratornim zatajenjem, ostaju i dalje najvažnija prijetnja životnom vijeku bolesnika. Do prije jednog desetljeća bilo je dostupno samo simptomatsko liječenje. Od 2012. g. dostupno je liječenje tzv. modulatorima CFTR-proteina i njihovim kombinacijama za osobe s cističnom fibrozom koje nose različite varijante CFTR-gena. Pojavom tih lijekova uvelike se promijenila perspektiva i kvaliteta života ljudi s cističnom fibrozom, ali postavljeni i novi izazovi u vezi s dugoročnim komplikacijama, pitanje eventualnog smanjenja konvencionalnog liječenja, ali i financiranja terapije, koja je mnogim bolesnicima nedostupna. Iznesene su bazične spoznaje o cističnoj fibrozi i funkciji CFTR-proteina, klasifikaciji varijanata CFTR-gena, mogućnostima liječenja CFTR-modulatorima te osnovni ishodi liječenja bolesnika s cističnom fibrozom u Hrvatskoj, gdje se ta terapija primjenjuje od jeseni 2021. godine.Cystic fibrosis, the most frequent lifespan shortening hereditary disease in Caucasians, is caused by a defect in the CFTR (cystic fibrosis transmembrane regulator) gene. Disturbed electrolyte homeostasis leads to the development of different symptoms in multiple organs. Pulmonary manifestations with chronic infections and inflammation result in respiratory failure and remain the most important life-shortening factor. Until recently only symptomatic treatment was available. In year 2012. a new treatment approach with small molecules that modulate the CFTR protein was introduced. Different combinations of CFTR modulators are applicable to certain patients carrying different variants of the CFTR gene. CFTR modulators made a huge difference in the quality of life and perspectives of people with cystic fibrosis. At the same time, new challenges emerged regarding long term complications and possible reduction of conventional treatment options, as well as financial issues that are an obstacle to the use of these drugs for many patients. This paper brings basic insight into cystic fibrosis, the function of CFTR protein, the classification of CFTR gene variants and possibilities of treatment with CFTR modulators as well as basic outcomes of CFTR modulators treatment in Croatia, where this therapy was introduced in autumn 2021

Uric acid and uric acid to creatinine ratio in the assessment of chronic obstructive pulmonary disease: Potential biomarkers in multicomponent models comprising IL-1beta.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease, with oxidative stress and inflammation implicated in its development. Uric acid (UA) could exert anti-oxidative, pro-oxidative or pro-inflammatory effects, depending on the specific context. It was recently shown that soluble UA, and not just its crystals, could activate the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to interleukin (IL)-1β secretion. We aimed to assess the differences in blood levels of UA and its ratio with creatinine (UCR) between COPD patients and healthy subjects, as well as their association with disease severity, smoking status, common COPD comorbidities and therapy regimes. The diagnostic characteristics of UA and UCR were also explored. This study included 109 stable COPD patients and 95 controls and measured white blood cells (WBC), C-reactive protein (CRP), fibrinogen (Fbg), IL-1β, creatinine (CREAT) and UA. All of the parameters were increased in COPD patients, except for CREAT. UA and UCR were positively associated with WBC, CRP and IL-1β. COPD smokers had lower UA and UCR values. Common COPD therapy did not affect UA or UCR, while patients with cardiovascular diseases (CVD) had higher UA, but not UCR, levels. Patients with higher UCR values showed worse disease-related outcomes (lung function, symptoms, quality of life, history of exacerbations, BODCAT and BODEx). Also, UCR differentiated patients with different severity of airflow limitation as well as symptoms and exacerbations. The great individual predictive potential of UCR and IL-1β was observed with their odds ratios (OR) being 2.09 and 5.53, respectively. Multiparameter models of UA and UCR that included IL-1β were able to correctly classify 86% and 90% of cases, respectively. We suggest that UA might be a useful biomarker when combined with IL-1β, while UCR might be even more informative and useful in overall COPD assessments

Platelet indices in stable chronic obstructive pulmonary disease – association with inflammatory markers, comorbidities and therapy

Introduction: Chronic obstructive pulmonary disease (COPD) is a complex inflammatory condition that can affect haemostasis. This study aimed to determine differences in platelet-related parameters between controls and COPD subjects. The hypothesis was that platelet indices are disturbed in COPD patients, and this would be accompanied by increased C-reactive protein (CRP), fibrinogen (Fbg) and white blood cells (WBC). Therefore, platelet count (Plt), platelet-related parameters – mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (Pct), their ratios (MPV/Plt, MPV/Pct, PDW/Plt, PDW/Pct), platelet to lymphocyte ratio (PLR), Plt index as well as CRP, Fbg and WBC were assessed. Materials and methods: Study included 109 patients with stable COPD and 95 control subjects, recruited at Clinical Department for Lung Diseases Jordanovac, University Hospital Centre Zagreb (Zagreb, Croatia). Complete blood count was performed on Sysmex XN-1000, CRP on Cobas c501, and Fbg on BCS XP analyser. Data were analysed with MedCalc statistical software. Results: Platelet (P = 0.007) and PLR (P = 0.006) were increased, while other platelet indices were decreased in COPD patients compared to controls. Combined model that included PLR, PDW and WBC showed great diagnostic performances, and correctly classified 75% of cases with an AUC of 0.845 (0.788 – 0.892), P < 0.001. Comorbidities (cardiovascular or metabolic diseases) had no effect on investigated parameters, while inhaled corticosteroids/long-acting β2-agonists (ICS/LABA) therapy increased MPV and PDW values in COPD patients. Conclusion: Platelet indices were altered in COPD patients and they could be valuable as diagnostic markers of COPD development, especially if combined with already known inflammatory markers

Profiling Colorectal Cancer in the Landscape Personalized Testing—Advantages of Liquid Biopsy

Drug-specific therapeutic approaches for colorectal cancer (CRC) have contributed to significant improvements in patient health. Nevertheless, there is still a great need to improve the personalization of treatments based on genetic and epigenetic tumor profiles to maximize the quality and efficacy while limiting cytotoxicity. Currently, CEA and CA 19-9 are the only validated blood biomarkers in clinical practice. For this reason, laboratories are trying to identify new specific prognostics and, more importantly, predictive biomarkers for CRC patient profiling. Thus, the unique landscape of personalized biomarker data should have a clinical impact on CRC treatment strategies and molecular genetic screening tests should become the standard method for diagnosing CRC. This review concentrates on recent molecular testing in CRC and discusses the potential modifications in CRC assay methodology with the upcoming clinical application of novel genomic approaches. While mechanisms for analyzing circulating tumor DNA have been proven too inaccurate, detecting and analyzing circulating tumor cells and protein analysis of exosomes represent more promising options. Blood liquid biopsy offers good prospects for the future if the results align with pathologists’ tissue analyses. Overall, early detection, accurate diagnosis and treatment monitoring for CRC with specific markers and targeted molecular testing may benefit many patients

Molecular Detection of Colorectal Cancer

Drug-specific therapeutic approaches for colorectal cancer (CRC) have contributed to a significant improvement in the health status of patients. However, a great need to improve personalization of treatments based on genetic and epigenetic tumor profiles to maximize quality and efficacy while limiting cytotoxicity remains. Currently, CEA and CA 19- 9 are the only validated blood biomarkers in clinical practice. For this reason, laboratories are trying to identify new specific prognostic and, more importantly, predictive biomarkers for CRC patient profiles. Thus, the unique landscape of personalized biomarker data should have a clinical impact on CRC treatment strategies and molecular genetic screening tests should become the standard method for CRC diagnosis, as well as detection of disease progression