Comparison of KRAS mutation status between primary tumor and metastasis in Chinese colorectal cancer patients

Li, Zhe Zhen; Bai, Long; Wang, Feng; Zhang, Zi Chen; Wang, Fang; Zeng, Zhao Lei; Zeng, Jun; Zhang, Dong Sheng; Wang, Zhi Qiang; Li, Yu Hong; Shao, Jian Yong; Xu, Rui‐Hua

doi:10.1007/s12032-016-0787-z

Cited by 14 publications

(19 citation statements)

References 46 publications

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“…We might postulate that targeted therapy against HSP90/ Topo I molecules expressed on the tumor cells, could improve the effectiveness of CRC treatment. In the present study, the results concerning KRAS mutation in CRC are in agreement with literature (9,10,11,26). The frequency of KRAS mutation in CRC with lymph node metastasis, noted in the current study, was also observed by other authors (9,26).…”

Section: Discussionsupporting

confidence: 93%

The Association Between HSP90/topoisomerase I Immunophenotype and the Clinical Features of Colorectal Cancers in Respect to KRAS Gene Status

Bär

Lis-Nawara

Grelewski

et al. 2017

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Section: Discussionsupporting

confidence: 93%

The Association Between HSP90/topoisomerase I Immunophenotype and the Clinical Features of Colorectal Cancers in Respect to KRAS Gene Status

Bär

Lis-Nawara

Grelewski

et al. 2017

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“…Moreover, the sample size and follow-up time need to be expanded and extended. Interestingly, clinical trials have shown that the outcome of patients with wild-type KRAS is significantly better than that of patients with KRAS mutations [24,25]. Our study obtained similar results according to RAS status for poor PFS.…”

Section: Discussionsupporting

confidence: 80%

Diagnostic, clinicopathologic, therapeutic and prognostic value of Plasma Heat Shock Protein 90 levels in patients with advanced Gastrointestinal Carcinoma

Zhang¹,

Ni²,

Li³

et al. 2020

J. Cancer

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Purpose: Heat shock protein 90 (HSP90) is a critical molecular chaperone for protein folding, intracellular disposition and regulation of tumor biological behavior in the extracellular space. HSP90 has received much attention due to its specific effect in gastrointestinal cancer. This clinical study sought to determine whether HSP90 in plasma may serve as a biomarker in patients with advanced gastrointestinal carcinoma. Methods: Using human plasma samples of advanced gastrointestinal carcinoma, we investigated the specific value of HSP90 in gastrointestinal cancer from a clinical perspective. Results: In summary, plasma levels of HSP90 were shown to be higher in patients with gastric cancer (GC) or colorectal cancer (CRC) than in controls with benign gastrointestinal diseases. In both GC and CRC patients, HSP90 was significantly associated with live metastasis. Higher HSP90 levels were more frequent in CRC patients with hazardous or harmful alcohol consumption habits. Patients with RAS mutations had higher HSP90 levels in CRC. Compared with Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 19-9 (CA19-9), HSP90 benefited patients by enhancing diagnostic sensitivity and the Youden index. The levels of HSP90 were inversely associated with short-term efficacy in GC patients who had received fluorouracil/platinum-based advanced first-line treatment. When first-line therapy failed, plasma HSP90 levels in patients with GC were significantly increased. In terms of progression-free survival (PFS), patients with GC or CRC who had low levels of HSP90 were not significantly different from those with high levels of HSP90. Univariate and multivariate analyses demonstrated that HSP90 was not an independent prognostic predictor for GC and CRC patients with PFS. However, RAS mutation was an independent prognostic factor for poor PFS in CRC patients. Conclusions: Plasma HSP90 levels have potential diagnostic value in advanced gastrointestinal carcinoma and therapeutic predictive value in GC.

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“…Tumor heterogeneity has been widely reported 23 - 26 . For example, the rate of discordance of KRAS mutation status between primary and metastatic tumors was about 20% in Chinese CRC patients according to our previous study 27 . In order to help explain the mechanism of inefficient predictive value of PD-L1 expression for benefit from anti-PD-1 treatment in CRC, we conducted this study to explore the clinicopathological and biomarker relevance and heterogeneity of PD-L1 expression within primary tumors and between primary and metastatic tumors in a relatively large CRC patient sample.…”

Section: Introductionmentioning

confidence: 78%

The Clinical and Biomarker Association of Programmed Death Ligand 1 and its Spatial Heterogeneous Expression in Colorectal Cancer

Wei

Chen

et al. 2018

J. Cancer

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Background: Programmed death ligand 1 (PD-L1) expression has been shown to predict benefit from anti-PD-1 treatment in several cancers. However, its predictive value in colorectal cancer seems limited. This study was aimed to explore the clinical and biomarker association of programmed death ligand 1 and its spatial heterogeneous expression in colorectal cancer.Methods: Tissue microarrays of 422 primary colorectal cancers from our hospital were used for the interpretation of PD-L1 and programmed death 1 (PD-1) expression, cluster of differentiation 4 (CD4) and CD8 density and microsatellite instability (MSI) status by immunohistochemistry. To assess the spatial heterogeneity of PD-L1 expression, Tissue microarrays of 383 paired intra-primary-tumor tissues, and 105 paired lymph node metastatic tumors and 64 paired distant metastatic tumors were also used.Results: PD-L1 was positive in 188 (44.5%) primary colorectal cancers. PD-L1 expression was associated with less advanced N category (P<0.001), less advanced TNM stage (P<0.001) and less nervous invasion (P=0.04). Higher PD-L1 expression was associated with higher PD-1 expression (P<0.001), higher CD4 (P<0.001) and CD8 (P<0.001) density and DNA mismatch repair deficiency (P=0.01). PD-L1 expression was associated with better disease-free survival and overall survival, but it was only an independent prognostic factor for disease-free survival (hazard ratio and 95% confidence interval: 0.42 [0.25-0.72], P<0.001). The probability of inconsistent PD-L1 expression was respectively 17.8%, 31.4% and 39.1% within primary tumors, between primary tumors and lymph node metastatic tumors, and between primary tumors and distant metastatic tumors. All the three differences were statistically significant (P<0.001, P<0.001 and P=0.05, respectively).Conclusions: PD-L1 expression was a marker of pre-existing immune responses in colorectal cancer, however, it was heterogeneously expressed in colorectal cancer, especially between primary and metastatic tumors. This might partially explain the low-efficiency of its predictive value for benefit from anti-PD-1 treatment.

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Comparison of KRAS mutation status between primary tumor and metastasis in Chinese colorectal cancer patients

Cited by 14 publications

References 46 publications

The Association Between HSP90/topoisomerase I Immunophenotype and the Clinical Features of Colorectal Cancers in Respect to KRAS Gene Status

The Association Between HSP90/topoisomerase I Immunophenotype and the Clinical Features of Colorectal Cancers in Respect to KRAS Gene Status

Diagnostic, clinicopathologic, therapeutic and prognostic value of Plasma Heat Shock Protein 90 levels in patients with advanced Gastrointestinal Carcinoma

The Clinical and Biomarker Association of Programmed Death Ligand 1 and its Spatial Heterogeneous Expression in Colorectal Cancer

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