A prognostic analysis of 895 cases of stage III colon cancer in different colon subsites

Zhang, Yan; Ma, Junli; Zhang, Sai; Deng, Geng; Wu, Xiaoling; He, Jingxuan; Pei, Haiping; Shen, Hong; Zeng, Shan

doi:10.1007/s00384-015-2273-z

Cited by 45 publications

(31 citation statements)

References 51 publications

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“…We did not find significant associations between NRAS mutation and patients’ survival, which was consistent with previous studies 12 13 36 . In multivariate analysis, tumor differentiation appeared independently prognostic value in colon cancer patients for stage III and combined together, poor differentiation indicated more malignant tumors, and the results were in accordance with a recent study 40 , though the tumor differentiation acted as prognostic for survival only in univariate analysis in their study.…”

Section: Discussionsupporting

confidence: 89%

Prognostic impact of mutation profiling in patients with stage II and III colon cancer

Shen

Han

Wang

et al. 2016

Sci Rep

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Development of colorectal cancer (CRC) associates with accumulation of genetic mutations include the epidermal growth factor receptor (EGFR) signaling pathway. However, whether mutations in KRAS together with downstream factors BRAF, PIK3CA and NRAS impact prognosis is still unclear for stage II-III colon cancer. In the present study a total of 228 stage II-III colon cancer samples were retrospectively collected, KRAS (codons 12, 13 and 61), BRAF (exon 11 and exon 15), PIK3CA (exon 9 and exon 20) and NRAS (codons 12, 13 and 61) status was detected by Sanger sequencing, 37.89% (86/227) tumors harbored a KRAS mutation, 7.02% (16/228) harbored a BRAF mutation, 13.18% (29/220) harbored a PIK3CA mutation and 0.89% (2/224) harbored a NRAS mutation. NRAS mutations existed only in stage II colon cancer. Older groups harbored a higher KRAS and BRAF mutation (P < 0.05), PIK3CA (exon9) mutations appeared more common in worse differentiation tumors (P = 0.032). Moreover, PIK3CA (E545K) mutation was significantly associated with tumor recurrence (P = 0.031) and acted independently prognostic for poor OS (P = 0.044), while only in stage III colon cancer. KRAS, BRAF and NRAS mutations do not have major prognostic value in stage II and III colon cancer, subtypes of gene mutations should be further investigated for a better understanding in CRC.

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Section: Discussionsupporting

confidence: 89%

Prognostic impact of mutation profiling in patients with stage II and III colon cancer

Shen

Han

Wang

et al. 2016

Sci Rep

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“…2,3 The majority of CRC patients in the advanced stage died of cancer recurrence and metastasis. 4 Epithelial-to-mesenchymal transition (EMT) is a significant molecular mechanism in the steps of distant metastasis by suppression of epithelial markers, up-regulation of mesenchymal markers. 5,6 EMT promotes cancer cells switching a polarized epithelium to a highly invasive mesenchymal phenotype, and it requires a succession of complicated cellular events including the loss of polarity and tight junctions, desmosomes and cytokeratin intermediate filaments, and the alteration in cytoskeletal architecture through the modulation of EMT-related factors.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of Beclin‐1 impairs epithelial‐mesenchymal transition of colon cancer cells

Shen

Yin

Deng

et al. 2018

J of Cellular Biochemistry

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Activation of autophagy significantly affects cancer cell behaviors, such as proliferation, differentiation, and invasiveness. Epithelial-to-mesenchymal transition (EMT) as an initial step of malignant transformation of cancer cells was linked to the activation of autophagy, but the detailed molecular mechanisms are still unknown. The present study investigates the effects of Beclin-1, a key molecule involved in activation of autophagy, on EMT of colon cancer cells. The normal colon epithelia cell line of CCD-18Co and six colon cancer cell lines with different expression levels of Beclin-1 were used in this study. The activation of autophagy and EMT markers of cancer cells were monitored by Western blotting and quantitative real-time PCR assay in the presence or absence of rapamycin (autophagy activator) and 3-MA (autophagy inhibitor). The expression of Beclin-1 in selected cell lines was modulated using small interfering RNA, and consequentially EMT markers, and cancer cell behaviors including migration and invasion, were also explored. Activation or inhibition of autophagy in colon cancer cells had positive or negative impacts on the expression of EMT markers and malignant behaviors such as cell migration and invasion. Knockdown of beclin-1 by siRNA apparently inhibited the activation of autophagy induced by rapamycin, consequentially resulted in suppression of EMT and attenuation of invasiveness of colon cancer cells. The results in this study demonstrated an association between activation of autophagy and EMT in colon cancer cells. The results showed suppression of Beclin-1 expression significantly reduced EMT and invasive behaviors in colon cancer cells.

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“…Globally colon cancer (CC) has the third highest rate of malignancy, which is associated with a high rate of mortality. In over one-third of patients with CC will evolve into metastatic disease with a five-year survival rate of only ~ 10% 1 . Chemotherapy using the third generation platinum drug oxaliplatin (OXA) improves overall survival (OS) for advanced or metastatic CC patients 2 .…”

Section: Introductionmentioning

confidence: 99%

ZEB1 Promotes Oxaliplatin Resistance through the Induction of Epithelial - Mesenchymal Transition in Colon Cancer Cells

Guo¹,

Ma²,

Deng³

et al. 2017

J. Cancer

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Background: Oxaliplatin (OXA) chemotherapy is widely used in the clinical treatment of colon cancer. However, chemo-resistance is still a barrier to effective chemotherapy in cases of colon cancer. Accumulated evidence suggests that the epithelial mesenchymal transition (EMT) may be a critical factor in chemo-sensitivity. The present study investigated the effects of Zinc finger E-box binding homeobox 1 (ZEB1) on OXA-sensitivity in colon cancer cells.Method: ZEB1expression and its correlation with clinicopathological characteristics were analyzed using tumor tissue from an independent cohort consisting of 118 colon cancer (CC) patients who receiving OXA-based chemotherapy. ZEB1 modulation of OXA-sensitivity in colon cancer cells was investigated in a OXA-resistant subline of HCT116/OXA cells and the parental colon cancer cell line: HCT116. A CCK8 assay was carried out to determine OXA-sensitivity. qRT-PCR, Western blot, Scratch wound healing and transwell assays were used to determine EMT phenotype of colon cells. ZEB1 knockdown using small interfering RNA (siRNA) was used to determine the ZEB1 contribution to OXA-sensitivity in vitro and in vivo (in a nude mice xenograft model).Result: ZEB1 expression was significantly increased in colon tumor tissue, and was correlated with lymph node metastasis and the depth of invasion. Compared with the parental colon cancer cells (HCT116), HCT116/OXA cells exhibited an EMT phenotype characterized by up-regulated expression of ZEB1, Vimentin, MMP2 and MMP9, but down-regulated expression of E-cadherin. Transfection of Si-ZEB1 into HCT116/OXA cells significantly reversed the EMT phenotype and enhanced OXA-sensitivity in vitro and in vivo.Conclusion: HCT116/OXA cells acquired an EMT phenotype. ZEB1 knockdown effectively restored OXA-sensitivity by reversing EMT. ZEB1 is a potential therapeutic target for the prevention of OXA-resistance in colon cancer.

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A prognostic analysis of 895 cases of stage III colon cancer in different colon subsites

Abstract: Stage III colon cancer located proximally carried a poorer survival than that located distally. Different efficacies of FOLFOX adjuvant chemotherapy may be an important factor affecting survival of site-specific stage III colon cancers.

Cited by 45 publications

References 51 publications

Prognostic impact of mutation profiling in patients with stage II and III colon cancer

Prognostic impact of mutation profiling in patients with stage II and III colon cancer

Knockdown of Beclin‐1 impairs epithelial‐mesenchymal transition of colon cancer cells

ZEB1 Promotes Oxaliplatin Resistance through the Induction of Epithelial - Mesenchymal Transition in Colon Cancer Cells

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