# Genetic Alteration Profiling in North Macedonian Lung Cancer Patients

## TL;DR

This study examines genetic mutations in lung cancer patients from North Macedonia to guide more effective treatment strategies.

## Contribution

The study provides a detailed genetic alteration profile of lung cancer in a specific regional population.

## Key findings

- 36.65% of patients had at least one genetic alteration, with KRAS and EGFR mutations being the most common.
- PD-L1 overexpression was observed in 10.45% of patients, while no ROS-1 rearrangements were detected.
- Co-occurring mutations were frequently found in KRAS and PIK3CA, KRAS and BRAF, or EGFR and PIK3CA.

## Abstract

Background/Objectives: Late diagnosis and inefficient treatment regimens lead to poor prognosis, with a low 5-year survival rate for both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). New targeted therapeutic agents can be developed and introduced only by first discovering new driver oncogenes and with a thorough investigation of the known driver genes. The aim of the current study is to investigate the prevalence of alterations in the eight most frequently altered genes in lung cancer—BRAF, EGFR, KRAS, ALK, ROS1, HER2, PD-L1 and PIK3CA. Methods: Real-time polymerase chain reaction (RT-PCR) was used to detect KRAS and EGFR mutations, multiplex PCR and microarray hybridization for KRAS/BRAF/PIK3CA mutations. Immunohistochemical analysis was performed for the detection of ALK, HER2/NEU, ROS-1 and PD-L1 alterations. Results: Overall, 221/603 patients (36.65%) had at least one genetic alteration, of which 22 patients (3.65%) had two genetic alterations and two patients had more than two genetic alterations. Additionally, 50 patients were identified with one or more KRAS mutations (8.29%), 45 patients with EGFR mutations (7.46%), and 1.82% with PIK3CA mutations and 0.66% with BRAF mutations. Furthermore, 50% of the co-occurring alterations were either on KRAS and PIK3CA genes (3/6), on KRAS and BRAF genes (2/6, 33.33%) or on EGFR and PIK3CA genes (1/6, 16.67%), and 10.45% of the patients exhibited PD-L1 overexpression, 5.31% ALK rearrangements, and 2.36% HER2/NEU expression, with no ROS-1 rearrangements detected. Conclusions: Comprehensive testing for somatic alterations in EGFR, BRAF, KRAS, and PIK3CA is significant in guiding therapeutic decisions in lung cancer management. Such testing should be routinely conducted to establish a thorough genetic profile of lung cancers in a manner that is both time-efficient and cost-effective.