Prognosis and Clinicopathology of CXCR4 in Colorectal Cancer Patients: a Meta-analysis

Li, Luning; Jiang, Kai-Tong; Tan, Peng; Wang, Aihua; Kong, Qing-Yin; Wang, Cui-Yue; Lu, Hua-Rong; Wang, Jing

doi:10.7314/apjcp.2015.16.9.4077

Cited by 19 publications

(11 citation statements)

References 21 publications

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“…In recent years, some molecular markers had been identified that were related to the survival rate of colorectal cancer patients, which may be helpful in the improvement of therapeutic strategies and survival rates of colorectal cancer patients. For example, APC promoter methylation may be a potential biomarker for the carcinogenesis of colorectal cancer [ 35 ], SMAD4 expression was a prognostic marker for survival in colorectal cancer patients [ 36 ], and the overexpression of CXCR4 reduced overall survival in colorectal cancer patients [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of p-STAT3 as a Prognostic and Clinicopathological Marker in Colorectal Cancer: A Systematic Review and Meta-Analysis

Zhang

Chu

et al. 2016

PLoS ONE

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ObjectiveHigh expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) has been detected in a variety of human tumors. However, the association of positive p-STAT3 expression with clinicopathological parameters and the prognosis of colorectal cancer patients remain controversial. To identify the relationship between p-STAT3 expression and clinicopathological parameters and prognosis in patients with colorectal cancer, a systematic review and meta-analysis were performed.MethodsWe performed a comprehensive literature search from PubMed, EMBASE, and SinoMed through 27 March, 2016. Hazard ratios (HRs) with 95% confidence intervals (CI) were combined to evaluate the association between p-STAT3 expression and overall survival of colorectal cancer patients. Odds ratios (ORs) with 95% CI were combined to evaluate the association between p-STAT3 expression and clinicopathological parameters in patients with colorectal cancer.ResultsSeventeen studies including a total of 2,346 colorectal cancer patients were included in this meta-analysis. The combined HR was 1.43 (95% CI: 1.23–1.67, P < 0.001), which suggested a positive relationship between p-STAT3 overexpression and poorer overall survival of colorectal cancer patients. In addition, the results indicated that positive p-STAT3 expression was significantly associated with the presence of lymph node metastasis (OR: 2.43, 95% CI: 1.18–5.01, P = 0.02) but was not associated with TNM stage, tumor differentiation or gender.ConclusionThe meta-analysis results suggest that p-STAT3 overexpression is unfavorable for the prognosis of colorectal cancer patients, and p-STAT3 overexpression is associated with the presence of lymph node metastasis among colorectal cancer patients.

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Section: Discussionmentioning

confidence: 99%

The Role of p-STAT3 as a Prognostic and Clinicopathological Marker in Colorectal Cancer: A Systematic Review and Meta-Analysis

Zhang

Chu

et al. 2016

PLoS ONE

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“…The chemokine protein CXCL12 (also known as SDF1) and its receptor CXCR4 are involved in the proliferation, differentiation, and migration of specific cells in the body. 17 The levels of CXCL12 are high in individual organs such as liver, brain, heart, and kidney. 18 Recently, studies have linked the CXCL12/CXCR4 biological axis to malignancy, 19 and elevated levels of SDF1 may be associated with an increased risk of malignancy.…”

Section: Introductionmentioning

confidence: 99%

The CXCL12 rs1801157 polymorphism and risk of colorectal cancer: a meta-analysis

Dai

Wang

et al. 2018

OTT

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BackgroundThe CXCL12 rs1801157 polymorphism is putatively associated with the risk of malignancy. However, research results are inconsistent regarding particular cancers, especially colorectal cancer (CRC).MethodsWe conducted a meta-analysis via a comprehensive literature search of the databases PubMed and Embase. Odds ratios and their corresponding 95% confidence intervals were extracted to assess comprehensively the association between the CXCL12 rs1801157 polymorphism and the risk of CRC.ResultsAccording to the following models, the correlation between the presence of the CXCL12 rs1801157 polymorphism and the risk of CRC was not statistically significant: allelic (G cf. A), heterozygous (GG cf. GA), homozygous (GG cf. AA), dominant (GG cf. GA+AA), or recessive (AA cf. GA+GG) for pooled calculating. However, in subgroup analysis, elevated risk of CRC was found in the non-Caucasian group in four genetic models, while no connection was found in the Caucasian group. The sensitivity analysis confirmed that the result of the Caucasian group was stable and analyzed the heterogeneity of the non-Caucasian group.ConclusionThis meta-analysis suggested that the CXCL12 rs1801157 polymorphism did not significantly confer a risk of CRC among Caucasians but may among non-Caucasians. These results warrant confirmation and further studies of different ethnic populations.

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“…7 The most frequent tumor differentiation was well differentiation (87.5%), this was concordant with previous meta-analysis studies. 12…”

Section: Characteristics Of Samplesmentioning

confidence: 99%

The Expression of CXCR4 and MMP13 in Colorectal Adenocarcinoma Dukes Stage A, B, C and D

Anggoro

Kusumastuti

2018

Indonesian Journal of Cancer

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Background: Colorectal adenocarcinoma is the third most common cancer in the world with increasing incidence in Indonesia. Most presented ones were in late stage with more unfavorable prognosis. It is necessary to evaluate new markers for prognosis, identify staging and new possibilities for targeted therapy. Over-proliferating tumor cells will enhance the expression of CXCR4, a chemokine receptor. Activating CXCR4 will further activate various downstream signaling pathways, including one which will increase MMP13 secretion through MAPK/ERK signaling pathway. MMP13 then will degrade extracellular matrix, thus facilitate the migration or metastasis of tumor cells. Methods: A cross sectional study, conducted on 32 samples of colorectal adenocarcinoma. The samples were divided into four groups based on the Dukes staging system (A, B, C and D) and stained immunohistochemically with antibody against CXCR4 and MMP13. The expressions were assessed using immunoreactive score (IRS) and were statistically analyzed. Results: There were positive correlation between the expression of CXCR4 and MMP13 with Dukes staging, with rs = 0,628 and rs = 0,597, respectively. The expression of CXCR4 positively correlated with the expression of MMP13 with rs = 0,670 (p = 0,05). Conclusions: CXCR4 and MMP13 expressions were proven to correlate with the depth of invasion and migration of tumor cells in colorectal adenocarcinoma, hence could be considered as prognostic markers, however both could not be used as predictive marker for staging. Tailored therapies targeting these two proteins could be an interest for further investigation. ABSTRAKLatar Belakang: Adenokarsinoma kolorektal adalah keganasan terbanyak ketiga di dunia, dengan insidensi semakin meningkat di Indonesia. Sebagian besar kasus terdeteksi pada stadium lanjut dengan prognosis buruk. Diperlukan penemuan marker baru yang dapat membantu penentuan stadium, prognosis dan kemungkinan terapi target yang baru. Sel tumor yang berproliferasi berlebihan akan menyebabkan peningkatan ekspresi CXCR4, suatu reseptor kemokin. Aktivasi CXCR4 akan meningkatkan pelepasan proteinase MMP13 melalui jalur MAPK/ERK. MMP13 akan mendegradasi matriks ekstraseluler sehingga menyebabkan migrasi atau metastasis sel tumor. Metode: Studi cross sectional, dilakukan pada 32 sampel adenokarsinoma kolorektal. Sampel dibagi menjadi 4 grup; stadium Dukes A, B, C dan D. Dilakukan pulasan imunohistokimia dengan antibodi CXCR4 dan MMP13, ekspresi keduanya dinilai menggunakan immunoreactive score (IRS) dan dianalisis secara statistik. Hasil: Didapatkan korelasi positif bermakna antara ekspresi CXCR4 dan MMP13 dengan stadium Dukes, dengan rs = 0,628 dan rs = 0,597. Ekspresi CXCR4 berkorelasi positif dengan ekspresi MMP13 dengan rs = 0,670 (p = 0,05). Kesimpulan: Ekspresi CXCR4 dan MMP13 terbukti berkorelasi dengan kedalaman invasi dan migrasi sel ganas pada adenokarsinoma kolorektal. Keduanya dapat dipertimbangkan sebagai marker prognostik namun tidak dapat digunakan sebagai marker prediktif stadium. Targeted therapy untuk kedua protein ini menarik untuk dilakukan investigasi lebih jauh.

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Prognosis and Clinicopathology of CXCR4 in Colorectal Cancer Patients: a Meta-analysis

Cited by 19 publications

References 21 publications

The Role of p-STAT3 as a Prognostic and Clinicopathological Marker in Colorectal Cancer: A Systematic Review and Meta-Analysis

The Role of p-STAT3 as a Prognostic and Clinicopathological Marker in Colorectal Cancer: A Systematic Review and Meta-Analysis

The CXCL12 rs1801157 polymorphism and risk of colorectal cancer: a meta-analysis

The Expression of CXCR4 and MMP13 in Colorectal Adenocarcinoma Dukes Stage A, B, C and D

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