Partial Oxygen Pressure Affects the Expression of Prognostic Biomarkers HIF‐1 Alpha, Ki67, and CK20 in the Microenvironment of Colorectal Cancer Tissue

Zhang, Lirong; Hu, Yu; Xi, Ning; Liu, Longding; Huang, Wenjing; Song, Shanshan; Liu, Yiting; Liu, Xianying; Xie, Ying

doi:10.1155/2016/1204715

Cited by 16 publications

(20 citation statements)

References 47 publications

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“…The average oxygen partial pressure of normal mammary tissue is 60 mmHg, whereas the average oxygen partial pressure in colon cancer tumors is 30 mmHg 49 . However, in patients with colon cancer, the degree of hypoxia in colon cancer tumor tissue is more obvious, with an average oxygen partial pressure of only approximately 10 mmHg 50 , 51 . Therefore, to verify the efficacy of the two-stage PFTBA@HSA oxygen delivery system, a more hypoxic CT26 colon cancer model was chosen to study the radio-sensitization effect of PFTBA@HSA.…”

Section: Resultsmentioning

confidence: 99%

Two-stage oxygen delivery for enhanced radiotherapy by perfluorocarbon nanoparticles

et al. 2018

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Tumors are usually hypoxic, which limits the efficacy of current tumor therapies, especially radiotherapy in which oxygen is essential to promote radiation-induced cell damage. Herein, by taking advantage of the ability of perfluorocarbon (PFC) to promote red blood cell penetration, we developed a simple but effective two-stage oxygen delivery strategy to modulate the hypoxic tumor microenvironment using PFC nanoparticles.Methods: We first examined the two-stage oxygen delivery ability of PFC nanoparticles on relieving tumor hypoxia through platelet inhibition. To evaluate the effect of PFC nanoparticles on radiation sensitization, CT26 tumor and SUM49PT tumor model were used.Results: In this study, PFC was encapsulated into albumin and intravenously injected into tumor-bearing mice without hyperoxic breathing. After accumulation in the tumor, PFC nanoparticles rapidly released the oxygen that was physically dissolved in PFC as the first-stage of oxygen delivery. Then, PFC subsequently promoted red blood cell infiltration, which further released O2 as the second-stage of oxygen delivery.Conclusion: The hypoxic tumor microenvironment was rapidly relieved via two-stage oxygen delivery, effectively increasing radiotherapy efficacy. The safety of all substances used in this study has been clinically demonstrated, ensuring that this simple strategy could be rapidly and easily translated into clinical applications to solve the clinical problems associated with tumor hypoxia.

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Section: Resultsmentioning

confidence: 99%

Two-stage oxygen delivery for enhanced radiotherapy by perfluorocarbon nanoparticles

et al. 2018

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“…A lower Ki67 expression at IF was associated with poor prognosis in Duke’s stage B CRC [ 36 ]. Additionally, the expression of Ki67 combined with HIF-1α and CK20 was predicted to be as prognostic biomarkers in the microenvironment of colorectal cancer tissue [ 37 ]. Therefore, it is questionable spatial Ki67 expression and its clinical prognosis.…”

Section: Discussionmentioning

confidence: 99%

Higher Ki67 expression in fibroblast like cells at invasive front indicates better clinical outcomes in oral squamous cell carcinoma patients

et al. 2018

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Background: Ki67 has been a key role for the treatment options and prognosis evaluation in some kinds of tumors; however, the spatial expression of Ki67 in oral squamous cell carcinoma (OSCC) has not been fully-evaluated. Therefore, in the present study, we aimed to elucidate the prognosis value of Ki67 spatial expression including in different cell types and at different compartments of tumor in OSCC patients. Methods: Immunohistochemical expression of Ki67 in tumor cells (TCs) and fibroblast like cells (FLCs) at center of tumor (CT) and invasive front (IF) was evaluated in 109 OSCC patients. Then correlations of Ki67 expressions with clinicopathological parameters were analyzed by Chi-square test, and survival curves were evaluated by Kaplan–Meier methods. Furthermore, univariate and multivariate analysis were performed to assess the diagnostic values of Ki67 expression by the Cox regression model. Results: Ki67 expression in TCs was much higher than in FLCs both at CT and IF compartments, but Ki67 expression in TCs was simultaneously higher at CT than that at IF (P=0.0004), which was converse to Ki67 expression in FLCs (P<0.0001). Additionally, high Ki67 expression in FLCs at IF was significantly associated with poor tumor differentiation (P=0.003), worse depth of invasion (DOI, P=0.027) and worst pattern of invasion (WPOI, P=0.041), but Ki67 expression in TCs had no correlation with clinical parameters no matter at CT or IF. Moreover, patients with higher Ki67 expression in TCs at CT had significantly increased risk for OS (overall survival; HR:1.935, 95% CI: 1.181–4.823, P=0.0395) and DFS (disease-free survival; HR: 2.974, 95% CI:1.189–5.023, P=0.046). On contrary, higher Ki67 expression in FLCs at IF was correlated with better OS (HR: 0.15, 95% CI: 0.018–0.846, P=0.0396) and DFS (HR: 0.15, 95% CI: 0.018–0.947, P=0.0445). Whereas, Ki67 expression both at TCs in IF and at FLCs in CT had no significant prognostic value for OS and DFS. Furthermore, Cox multivariate analysis revealed that Ki67 expression in FLCs at IF could not be an independent prognostic factor for OSCC patients. Conclusion: These results show that higher Ki67 expression in FLCs at IF indicated better clinical outcomes for OSCC patients.

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“…Several studies reported that gene mutation and protein expression of P53 differed significantly between RSCC and LSCRC 26 , 28 , 29 , but others showed that no significant association was identified between p53 protein expression and tumor site 30 . Ki67 is a marker of cell proliferation, and it plays a vital role in the development of CRC 31 . High Ki67 labeling index had been reported to be an independent prognostic biomarker in TNM III and IV CRC 32 .…”

Section: Introductionmentioning

confidence: 99%

Differences of protein expression profiles, KRAS and BRAF mutation, and prognosis in right-sided colon, left-sided colon and rectal cancer

Xian

Gong

et al. 2017

Sci Rep

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To compare protein expression levels, gene mutation and survival among Right-Sided Colon Cancer (RSCC), Left-Sided Colon Cancer (LSCC) and rectal cancer patients, 57 cases of RSCC, 87 LSCC and 145 rectal cancer patients were included retrospectively. Our results demonstrated significant differences existed among RSCC, LSCC and rectal cancer regarding tumor diameter, differentiation, invasion depth and TNM stage. No significant difference was identified in expression levels of MLH1, MSH2, MSH6, PMS2, β-Tubulin III, P53, Ki67 and TOPIIα, and gene mutation of KRAS and BRAF among three groups. Progression Free Survival (PFS) of RSCC was significantly lower than that of LRCC and rectal cancer. In univariate analyses, RSCC, preoperative chemoradiotherapy, poor differentiation, advanced TNM stage, elevated serum CEA and CA19-9 level, tumor deposit, perineural and vascular invasion were found to be predictive factors of shorter PFS. In multivariate analyses, only differentiation and TNM stages were found to be independent predictors of PFS. In conclusion, compared with LSCC and rectal cancer, RSCC has larger tumor size, poor differentiation, advanced TNM stage and shorter survival. The shorter survival in RSCC might be attributed to the advanced tumor stage caused by its inherent position feature of proximal colon rather than genetic difference.

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Partial Oxygen Pressure Affects the Expression of Prognostic Biomarkers HIF‐1 Alpha, Ki67, and CK20 in the Microenvironment of Colorectal Cancer Tissue

Cited by 16 publications

References 47 publications

Two-stage oxygen delivery for enhanced radiotherapy by perfluorocarbon nanoparticles

Two-stage oxygen delivery for enhanced radiotherapy by perfluorocarbon nanoparticles

Higher Ki67 expression in fibroblast like cells at invasive front indicates better clinical outcomes in oral squamous cell carcinoma patients

Differences of protein expression profiles, KRAS and BRAF mutation, and prognosis in right-sided colon, left-sided colon and rectal cancer

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