Features of the immunophenotype of cancer stem cells in different stages of colorectal cancer

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Abstract

This study examines the immunophenotype characteristics of the stem cell population in colon adenocarcinoma at various stages of the disease and evaluates their impact on the prevalence of the oncological process. The research involved analyzing surgical specimens from 67 patients with histologically confirmed colon adenocarcinoma using microscopic and immunohistochemical techniques. The patients were divided into two groups based on the extent of the neoplastic process. The first group consisted of 32 patients with localized colorectal cancer (T3–4aN0M0), while the second group included 35 patients with colorectal cancer with synchronous monoorgan liver metastases (T3–4aN0–2M1a (hep)).The study assessed the immunophenotype of the tumor and investigated its correlation with the disease stage. The analysis revealed no significant correlation between the proliferative activity index of the immunohistochemical marker Ki67 and the stage of the disease (p = 0.108). However, when comparing the immunophenotype of stem tumor cells in the group of patients with metastatic colorectal cancer, statistically significantly higher levels of expression were observed for the following immunohistochemical markers: ALDH1+ (p = 0.028), ALDH1+Ki67+ (p = 0.0002), and CXCR4+ (p = 0.005). These results indicate a strong association between immunohistochemical markers characterizing the stem cell population and the prevalence of the tumor. Therefore, markers such as ALDH1+, ALDH1+Ki67+, and CXCR4+ can provide valuable insights into the molecular and biological properties of stem tumor cells, aiding in the clinical assessment of the potential aggressiveness of colon adenocarcinoma. The study also found that the median stem cell proliferation index, which considers the proportion of proliferating cells only within the stem cell population and not the entire cell pool, in the group of patients with localized colorectal cancer was 16%. Notably, none of the patients in stage II of the disease had a stem cell proliferation level below 50%, and the stem cell proliferation index ranged from 0% to 50%. Notably, none of the patients in stage II of the disease had a stem cell proliferation level below 50%, and the stem cell proliferation index varied from 0% to 50%. In contrast, the median index of stem cell proliferation in the group of patients with metastatic colorectal cancer was 45.5%, with values ranging from 7% to 100%. The stem cell proliferation index in this group was significantly higher (p = 0.00001) than that in the group with localized tumor processes. Considering the small population of stem tumor cells, determining the index of stem cell proliferation is advisable for a more accurate assessment of their proliferative activity.

About the authors

Nikolay A. Maistrenko

Kirov Military Medical Academy

Email: nik.m.47@mail.ru
ORCID iD: 0000-0002-1405-7660
SPIN-code: 2571-9603

MD, Dr. Sci. (Med.), professor

Russian Federation, Saint Petersburg

Vadim S. Chirsky

Kirov Military Medical Academy

Email: v_chirsky@mail.ru
ORCID iD: 0000-0003-3215-3901
SPIN-code: 7295-3369

MD, Dr. Sci. (Med.), professor

Russian Federation, Saint Petersburg

Alina A. Erokhina

Kirov Military Medical Academy

Author for correspondence.
Email: lokitrikster@yandex.ru
ORCID iD: 0000-0001-7343-5089
SPIN-code: 1768-8760

pathologist

Russian Federation, Saint Petersburg

Aleksey A. Sazonov

Kirov Military Medical Academy

Email: sazonov_alex_doc@mail.ru
ORCID iD: 0000-0003-4726-7557
SPIN-code: 4042-7710

MD, Dr. Sci. (Med.)

Russian Federation, Saint Petersburg

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Supplementary files

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2. Fig. 1. Differential components of colon adenocarcinoma. Double immunohistochemical staining with antibodies to ALDH1 and Ki-67, with hematoxylin counterstaining. Magnification × 400. The arrows indicate the studied populations of tumor cells: 1 — stem proliferating (ALDH1+Ki-67+); 2 — stem nonproliferating (ALDH1+Ki-67−); 3 — progenitor cells (ALDH1–Ki-67+); 4 — differentiating (ALDH1–Ki-67–)

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3. Fig. 2. IImmunohistochemical study of type 4 chemokine receptors (CXCR4). Positive cytoplasmic granular reaction. Magnification × 200

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4. Fig. 3. Expression of ALDH1 at various stages of colorectal cancer (p = 0.028)

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5. Fig. 4. Structure of tumor components at various stages of colorectal cancer

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6. Fig. 5. Stem cell proliferation index at various stages of colorectal cancer

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7. Fig. 6. Expression of CXCR4 at various stages of colorectal cancer

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8. Fig. 7. Correlation of the stem cell proliferation index with the index of CXCR4 metastasis potential in patients with stage II colorectal cancer

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9. Fig. 8. Correlation of the stem cell proliferation index with the index of CXCR4 metastasis potential in patients with stage IV colorectal cancer

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