Chemokine CXCL8 and its receptors as markers of colorectal cancer



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Abstract

BACKGROUND: The chemokine CXCL8 and its receptor are involved in the activation and transport of inflammatory mediators and regulate the proliferation and renewal of cancer stem cells in colon cancer. It is believed that CXC signaling may be associated with poor prognosis in colorectal cancer.

AIM: To study the possibilities of using CXCL8-CXCR1/2 pathway indicators as markers in colorectal cancer.

MATERIAL AND METHODS: Isolation of ribonucleic acid (RNA) from histological sections of tumors obtained intraoperatively from 59 patients diagnosed with colorectal cancer was carried out using magnetic particles, and quantitative polymerase chain reaction in real time was performed. Calculation of the normalized expression of the CXCL8 and CXCR1 genes relative to the referee gene was done using special software. Statistical data processing was performed using Statistica 3.0, BioStat v. 7.1 programs. Comparisons of characteristics were performed using the Mann–Whitney U test. Cox and Kaplan–Meier criteria were used to analyze overall and disease-free survival.

RESULTS: The expression of CXCL8 in intestinal adenocarcinoma cells with low differentiation [Me (Q1–Q3) — 8.770 (1.127–1.114)] was significantly higher than in the groups of moderately and well differentiated tumors (p=0.004 and p=0.012, respectively); and in tumor tissue refractory to chemotherapy, it was significantly higher [4.374 (2.052–7.045)] compared to resistant [2.200 (1.388–5.037); p=0.008] and sensitive [1.624 (0.739–2.586); p=0.042]. The level of CXCR1 messenger RNA in tumor tissue was increased in the presence of BRAF mutation [3.645 (0.801–1.090); p=0.009] and low tumor differentiation [6.965 (3.938–12.225); p=0.002], as well as in tumor tissue refractory to FOLFOX/XELOX chemotherapy [46.224 (27.580–83.570); p=0.0009].

CONCLUSION: Expression of components of the CXCL8-CXCR1/2 signaling pathway in tumor tissue may be a marker of sensitivity to FOLFOX/XELOX chemotherapy in colorectal cancer.

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About the authors

Irina A. Bogomolova

Federal Scientific and Clinical Center for Medical Radiology and Oncology of the Federal Medical and Biological Agency of Russia

Author for correspondence.
Email: 73bogomolova@gmail.com
ORCID iD: 0000-0003-3331-8632

M.D., Head of Depart., Depart. of Antitumor Drug Therapy

Russian Federation, Dimitrovgrad

Inna I. Antoneeva

Ulyanovsk State University; Regional Clinical Oncology Dispensary

Email: aii72@mail.ru
ORCID iD: 0000-0002-1525-2070

M.D., D. Sci. (Med.), Prof., Depart. of Oncology and Radiation Diagnostics; Head of Depart., Depart. of Gynecology

Russian Federation, Ulyanovsk; Ulyanovsk

Dinara R. Dolgova

Ulyanovsk State University

Email: dolgova.dinara@yandex.ru
ORCID iD: 0000-0001-5475-7031

Cand. Sci. (Biol.), Assoc. Prof., Depart. of Physiology and Pathophysiology, Director of the Scientific ­Research Medical and Biological Center

Russian Federation, Ulyanovsk

Tatyana V. Abakumova

Ulyanovsk State University

Email: taty-abakumova@yandex.ru
ORCID iD: 0000-0001-7559-5246

D. Sci. (Biol.), Prof., Depart. of Physiology and Pathophysiology

Russian Federation, Ulyanovsk

Tatyana P. Gening

Ulyanovsk State University

Email: Naum-53@yandex.ru
ORCID iD: 0000-0002-5117-1382

D. Sci. (Biol.), Prof., Head of Depart., Depart. of Physiology and Pathophysiology

Russian Federation, Ulyanovsk

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Supplementary files

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2. Fig. 1. Progression-free time curve of patients with colorectal cancer depending on CXCL-8 expression in the tumor

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3. Fig. 2. ROC curve characterizing the dependence of the probability of the “group” indicator on the CXCL8 indicator

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4. Fig. 3. Progression-free time curve in patients with colorectal cancer depending on CXCR1 expression in the tumor

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5. Fig. 4. ROC curve characterizing the dependence of the probability of the “group” indicator on the CXCR1 indicator

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