Large Bowel Genetic Background and Inflammatory Processes in Carcinogenesis – Systematic Review

Szylberg, Łukasz; Janiczek, Marlena; Popiel, Aneta; Marszałek, Andrzej

doi:10.17219/acem/31239

Cited by 13 publications

(4 citation statements)

References 34 publications

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“…37 Tumor-associated macrophages (TAMs) are one of the sources of cytokines, and their released IL-10 levels increase in patients with CRC, especially in advanced stages. 65 Yan et al found a correlation between a high TAM count in gastric cancer and its progression, related to EMT. 66 IL-4, one of the anti-inflammatory cytokines produced by T cells, inhibits the expression of E-cadherin and carcinoembryonic antigen (CEA), and its levels are increased in patients with CRC compared to healthy patients.…”

Section: Discussionmentioning

confidence: 99%

<p>The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma</p>

Briede¹,

Štrumfa²,

Vanags³

et al. 2020

JIR

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Background: Inflammation plays an important albeit dual role in carcinogenesis. Survival studies have highlighted the prognostic significance of peritumorous inflammation. Currently, the theoretical background allows inflammation, epithelial mesenchymal transition (EMT) and the closely associated stem cell differentiation in colorectal carcinoma (CRC) to be linked. However, there is scarce direct morphological evidence. Purpose and methods: The aim of our study was to investigate the role of inflammation in cancer growth and invasion by analyzing the association between inflammation and known morphological prognostic features of colorectal cancer, EMT, stemness and mismatch repair (MMR) protein expression. The study was designed as a retrospective morphological and immunohistochemical assessment of 553 consecutive cases of surgically treated primary CRC. Results: There were statistically significant associations between high-grade inflammation and lower pT (p = 0.002), absence of lymph node metastases (p < 0.001) and less frequent lymphatic (p = 0.003), venous (p = 0.017), arterial (p = 0.012), perineural (p = 0.001) and intraneural (p = 0.01) invasion. In contrast, Crohn's like reaction (CLR) by density of lymphoid follicles in the invasive front lacked significant differences in regard to pT, pN, tumor invasion into surrounding structures (blood or lymphatic vessels, nerves), grade or necrosis (all p > 0.05). The expression of E-cadherin, CD44 and MMR proteins yielded no statistically significant associations with peritumorous inflammation by Klintrup-Mäkinen score or the density of lymphoid follicles. Nevertheless, E-cadherin levels were significantly associated with the density of eosinophils (p = 0.007). Conclusion: High-grade peritumorous inflammation is associated with beneficial morphologic CRC features, including less frequent manifestations of invasion, and is not secondary to tissue damage and necrosis. CLR is not associated with cancer spread by pTN; this finding indirectly suggests an independent role of CLR in carcinogenesis. Further, inflammation by Klintrup-Mäkinen grade and CLR is not dependent on epithelial-mesenchymal transition and stem cell differentiation. Our study highlights the complex associations between inflammation, tumor morphology, EMT, stemness and MMR protein expression in human CRC tissues.

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Section: Discussionmentioning

confidence: 99%

<p>The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma</p>

Briede¹,

Štrumfa²,

Vanags³

et al. 2020

JIR

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“…Although genetics likely play an important role in tumorigenesis, the inflammatory process is initiated by the movement of innate immune system cells to the microenvironment, followed by the secretion of proinflammatory cytokines, growth factors, and reactive oxygen species, causing DNA damage and promoting neoplastic development, as has been found in many tumor types [6]. Our multivariable analysis revealed that five independent baseline factors (neutrophilia, thrombocytosis, hypoalbuminemia, body mass index <30 kg/m 2 , and the absence of lung metastasis) were able to predict individual outcome not only in patients with KRAS+ / TP53+ mutant cancer who had received therapy in a phase I clinical trial, but also in those who had not received therapy.…”

Section: Discussionmentioning

confidence: 99%

“…However, KRAS mutation alone, which occurs in the early process of tumorigenesis, is not sufficient to induce malignant transformation of normal epithelial cells [5, 6]. Additional loss of tumor suppressor genes, such as TP53 [7, 8], is required for cancer development, which arises through sequential accumulation of oncogenic mutations and loss of tumor suppressor genes.…”

Section: Introductionmentioning

confidence: 99%

Antiangiogenesis and gene aberration-related therapy may improve overall survival in patients with concurrent KRAS and TP53 hotspot mutant cancer

et al. 2017

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PurposeGenetic alterations such as activating KRAS and/or inactivating TP53 are thought to be the most common drivers to tumorigenesis. Therefore, we assessed phase I cancer patients with KRAS+/TP53+ mutations.ResultsApproximately 8% of patients referred to phase I clinical trials harbored concurrent KRAS and TP53 mutations. Patients who received a phase I trial therapy (n = 57) had a median OS of 12 months, compared with 4.6 months in those who were not treated (n = 106; p = 0.003). KRAS G13 and TP53 R273 mutations were associated with poor overall survival (OS), while antiangiogenesis and gene aberration-related therapies were associated with prolonged OS. A prognostic model using neutrophilia, thrombocytosis, hypoalbuminemia, body mass index <30 kg/m2, and the absence of lung metastasis was established and validated. Phase I cancer patients in the low-risk group had a median OS of 16.6 months compared with 5.4 months in the high-risk group (p < 0.001). Untreated patients in the low-risk group had a median OS of 6.7 months compared with 3.6 months in the high-risk group (p = 0.033).Experimental DesignWe analyzed 163 consecutive patients with advanced KRAS+/TP53+ mutant cancer who were referred to phase I clinical trials, to identify molecular aberrations, clinical characteristics, survivals, and potentially effective treatment regimens.ConclusionsThis study provided preliminary evidence that besides modulation of the proinflammatory state, antiangiogensis and concomitant gene aberration-related therapies may improve the treatment of KRAS+/TP53+ mutant cancer.

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“…Another important cytokine is IL-4. It is secreted by activated T-cells and is associated with CRC progression [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Expression of COX-2, IL-1β, TNF-α and IL-4 in epithelium of serrated adenoma, adenoma and hyperplastic polyp

Szylberg¹,

Janiczek²,

Popiel³

et al. 2016

aoms

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IntroductionColon polyps and inflammatory process play the key role in neoplasia of colorectal cancer. In recent years there have been many publications on the malignancy of hyperplastic polyp (HP) which according to the WHO classification is a non-neoplastic polyp. The aim of this study is to determine the expression of inflammatory proteins COX-2, IL-1β, TNF-α and IL-4 in the epithelium of colorectal polyps.Material and methodsIn the study, 144 colorectal polyps were analyzed. The groups of HP, classical (A) and serrated adenomas (SA) and normal mucosa (control) according to histopathological studies were selected. Immunohistochemical examinations Rusing antibodies against COX-2, IL-1β, TNF-α and IL-4 were performed. The expression of analyzed protein was evaluated using modified Remmele-Stegner scale (0-16).ResultsStatistical analysis revealed higher expression of TNF-α (16 ±3.87 vs. 1 ±5.06), IL-1β (12 ±4 vs 8 ±2.72), COX-2 (9 ±2.54 vs. 8 ±3.14) and IL-4 (12 ±3.45 vs. 4 ±3.35) in SA polyps compared to the control (p < 0.001). The HP had an increased level of expression of TNF-α (12 ±3.72 vs. 1 ±5.06, p < 0.005), COX-2 (8.5 ±1.97 vs. 8 ±3.14, p < 0.012) and IL-4 (12 ±3.46 vs. 4 ±3.35, p < 0.001). Significantly higher expression of IL-4 (12 ±2.32 vs. 4 ±3.35, p < 0.001) and IL-1β (16 ±4.32 vs. 8 ±2.72, p < 0.044) in A compared to the control were observed.ConclusionsExpression of inflammatory factors differed between polyps. Inflammation accompanied the serrated structures which occur in polyps. The inflammatory process affects the development of colorectal polyps. The HP may predispose to malignancy.

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Large Bowel Genetic Background and Inflammatory Processes in Carcinogenesis – Systematic Review

Cited by 13 publications

References 34 publications

<p>The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma</p>

<p>The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma</p>

Antiangiogenesis and gene aberration-related therapy may improve overall survival in patients with concurrent KRAS and TP53 hotspot mutant cancer

Expression of COX-2, IL-1β, TNF-α and IL-4 in epithelium of serrated adenoma, adenoma and hyperplastic polyp

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