Naslov
The role of Interleukin-7 serum levels as a biological marker in breast cancer

Autori
Sermaxhaj, Faton

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, doktorska disertacija

Fakultet
Medicinski fakultet

Mjesto
Zagreb

Datum
16.02

Godina
2023

Stranica
86

Mentor
Dedić Plavetić, Natalija

Ključne riječi
interleukin 7 ; breast cancer ; serum ; Croatia ; Kosovo

Sažetak
Background: The important role that the immune system has in malignant diseases is well-known. The action of Interleukin-7(IL-7) as a cytokine, has been observed in many cellular processes, both in normal cells of the immune system and in some cancer cells. The aim of this study has been to explore whether there is any elevation of Interleukin-7 serum level in the early invasive breast cancer (EIBC) patients in comparison with healthy controls. The correlation between the IL-7 serum level and histopathological characteristics of the tumor, has been evaluated. In addition, the clinical, histopathological and molecular characteristics of primary operabale breast cancer patients from Croatia and Kosovo were explored, in order to compare the disease stage at the time of diagnosis between patients of these two countries. Methods: This cross-sectional, observational, and analytical study has included 213 consecutive patients with EIBC (113 from Croatia and 100 from Kosovo) and 62 healthy participants as the control group (30 from Croatia and 32 from Kosovo). Blood samples have been taken from patients confirmed with breast cancer (BC) by biopsy, prior to surgical intervention and other oncological treatments, as well as from healthy participants. IL-7 serum level has been measured, using “Sandwich” ELISA Immunoenzyme test. In addition, after the surgical intervention, the histopathological specimen examinations and the immunohistochemistry have been performed and analyzed. The age and menopausal status of the patients were recorded before surgery. After checking for normality of distribution, numerical variables have been presented as median and interquartile range. The differences of the distribution of the numerical variables have been analyzed with Mann-Whitney U test and Kruskal-Wallis ANOVA test. Associations between numerical variables have been analyzed as Spearman rank correlation coefficient. The diagnostic accuracy and the optimal cut point value for IL-7 level between two groups have been obtained based on the value of the area under the ROC curve. Categorical variables were compared using chi-square analysis and presented as frequencies and percentages. The results were calculated as the mean and standard deviation or median and range. Analyses have been performed with statistical software SPSS-22.0. A P-value < 0.05 was considered statistically significant. Results: The IL-7 serum level in the EIBC patients has been significantly higher compared to the control cases (P<0.001). Regarding the EIBC patients, there have been no correlations between IL-7 serum level and tumor size, age, and Ki-67 (%) (Spearman’s R = 0.5, P = 0.4, Spearman’s R = 0.5, P = 0.6 and Spearman’s R = 0.3, P = 0.7, respectively). Patients with invasive lobular carcinoma (ILC) seems to have lower IL-7 serum level compared to other histological subtypes, and the difference is significant (P=0.043). There have been no significant differences of IL-7 serum level between different stages of disease, molecular surrogate subtypes, and histological grade. Immunohistochemical expression or absence of molecular markers, such as PR, ER, amplification of Her-2/neu receptor and proliferation index as measured by Ki-67, as well as LVI and PNI, have been not correlated with IL-7 serum level. The median age at diagnosis for patients from Kosovo and Croatia was 54 and 57, respectively (P=0.17). The percentage of premenopausal women included in the study was 33% and 37% in Kosovo and Croatia, respectively (P=0.97). The median tumor size at diagnosis was significantly larger in subjects from Kosovo than in those from Croatia (P<0.01). The number of total and metastatic lymph nodes was also significantly increased in Kosovo patients (P=0.02). The rate of LVI was significantly increased in Kosovo patients (P<0.01), while the expression of PR was higher in Croatian patients, the difference is significant (P=0.01). Differences were noticed between the two cohorts regarding Her-2/neu amplification status, with higher rate in Kosovo cohort, but this tendency did not reach statistical significance (P=0.07). The histological types did not significantly differ between the two groups. Invasive breast carcinoma (NST) was the most common type with a frequency of approximately 75% in both countries. Histological grade, Ki-67 proliferation index, ER status and distribution of molecular subtypes were not significantly different when compared in subjects living in Kosovo or Croatia. Conclusion: Noticing the significant increase of the IL-7 serum level in the EIBC patients compared to healthy control group, the use of IL-7 as a potential diagnostic indicator for BC can be assumed. The lack of correlation with tumor size, lymph node metastasis, as well as all other histopathological characteristics of the tumor, questions its use as a prognostic indicator. The BC patients from Kosovo are diagnosed at a more advanced stage of the disease than BC patients from Croatia. Considering the geographical proximity between two countries and the adoption of a similar lifestyle in both countries, it may be assumed that this situation is related to the lack of community-based mammography screening, lack of education and low BC awareness in Kosovo.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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