The somatic mutation landscape of Chinese Colorectal Cancer

Ma, Rong; Jing, Changwen; Zhang, Yuan; Cao, Hongyan; Liu, Siwen; Wang, Zhuo; Chen, Dan; Zhang, Junying; Wu, Yang; Wu, Jianzhong; Feng, Jifeng

doi:10.7150/jca.37017

Cited by 20 publications

(21 citation statements)

References 46 publications

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“…Fc fragment of IgG-binding protein (FCGBP) may represent one such protein marker as its expression is low in some tumors, while high in others [ 2 – 4 ]. For example, expression of FCGBP is low in gallbladder cancer, in which it serves as a key regulator of tumor growth factor 1 (TGF-1)-induced epithelial-mesenchymal transition [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

A bioinformatic analysis: the overexpression and clinical significance of FCGBP in ovarian cancer

Wang

Guan

Shang

et al. 2021

Aging

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Fc fragment of IgG-binding protein (FCGBP) is differentially expressed in various tumors. However, the correlation between FCGBP and immune cell infiltration in ovarian cancer remains unclear. FCGBP expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data, and the ovarian cancer expression profile was analyzed using the Gene Expression Omnibus database. The clinical prognostic value of FCGBP was evaluated using clinical survival data from TCGA. Enrichment analysis of FCGBP was performed using the R package clusterProfiler. Based on known immune cell infiltration scores for samples found in TCGA, we analyzed the association between immune cell infiltration level and FCGBP expression. FCGBP was highly expressed and associated with poorer overall survival (p = 0.00051) and disease-specific survival (p = 0.0012) in ovarian cancer and other tumors. Additionally, high FCGBP expression correlated significantly with immune-related gene sets, including those involved in chemokine signaling pathways and innate and adaptive immunity. Further analysis showed that M2 macrophage infiltration increased and M1 macrophage infiltration decreased in tissues with high FCGBP expression. Our study suggests that FCGBP contributes to M2 macrophage polarization by acting as an oncogene in ovarian cancer. FCGBP may represent a clinically helpful biomarker for predicting overall survival of ovarian cancer patients.

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Section: Introductionmentioning

confidence: 99%

A bioinformatic analysis: the overexpression and clinical significance of FCGBP in ovarian cancer

Wang

Guan

Shang

et al. 2021

Aging

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“…Ma et al performed whole exome-sequencing analysis of 63 CRC cases, and found that with the deficiency of FCGBP , CRC developed and showed worse survival rates. 17 At stage I or II CRC, FCGBP was reported to be positively associated with the prognosis of CRC. 18 Onstenk et al measured CTCs of liver metastasis in CRC patients and their primary tumor tissues and found that FCGBP was down-regulated.…”

Section: Discussionmentioning

confidence: 99%

IgG Fc Binding Protein (FCGBP) is Down-Regulated in Metastatic Lesions and Predicts Survival in Metastatic Colorectal Cancer Patients

Yuan¹,

Zhao

Hu³

et al. 2021

OTT

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Background: The liver is the most frequent site for metastatic spread in colorectal cancer (CRC) patients, and these patients have much poorer prognosis than those without metastasis. Previous studies have shown that IgG Fc binding protein (FCGBP) plays important roles in tumorigenesis, progression, and prognosis, but its role in CRC metastasis remains unclear. Purpose: In this study, we are aimed to explore the significance of FCGBP in liver metastatic CRC (LMCRC) patients. Methods: We analyzed the expression of FCGBP RNA between CRC primary samples and liver metastatic samples in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA). Next, we assessed the expression of FCGBP protein in 135 paired primary CRC (PC) samples and LMCRC samples. Finally, we explored the relationship between the expression features and clinicopathological characteristics. Results: The expression data of FCGBP were obtained from the GEO and TCGA databases. FCGBP RNA expression was evaluated between primary lesions (PC) and liver metastatic lesions (LM). FCGBP RNA was down-regulated in PC and LM, and especially lower in LM (p<0.001). Next, the expression of FCGBP protein was evaluated by an immunohistochemistry array in 135 paired primary tumor tissues and metastatic tissues. We found that FCGBP protein was down-regulated in primary lesions and metastatic lesions, especially in metastatic lesions. According to the immunohistochemistry score (SI), each cohort was divided into FCGBP-positive (SI=4-12) and FCGBP-negative (SI=0-3) groups. In both groups, the levels of CEA (PC group, 3.880 vs 77.049, p<0.001; LM group, 3.890 vs 14.239, p=0.008) and CA19-9 (PC group, 8.610 vs 111.700, p<0.001; LM group, 7.660 vs 19.380, p=0.037) were lower than those in the FCGBP-negative group. FCGBP positivity in the LM cohort was an independent risk factor in both overall survival (HR 1.573, 95% Cl [1.017-2.433], p=0.042) and disease-free survival (HR 1.869, 95% Cl [1.256-2.781], p=0.002). Conclusion: This study found a relationship between FCGBP expression and clinical information of LMCRC patients, and found that FCGBP expression decreased with disease development. The expression of FCGBP in liver metastasis is associated with both the overall and progressionfree survival. Our results show that FCGBP could be a promising prognostic factor for LMCRC.

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“…Defective variants in POLD1 and POLE , essential genes in the BER pathway, are related to significantly higher mutational burden and malignancy through BER’s correlation to the MMR pathway ( 47 ). Co-mutations in the MMR and HRR pathways may also be related to hypermutated CRC with worse survival, via interruption of DNA binding and replication ( 48 ). Our study reveals that beyond each single DDR pathway mutations, the co-mutations and the number of mutated DDR pathways are also significantly related to post-operative survival, and the correlations were independent of other clinical traits.…”

Section: Discussionmentioning

confidence: 99%

Mutated DNA Damage Repair Pathways Are Prognostic and Chemosensitivity Markers for Resected Colorectal Cancer Liver Metastases

et al. 2021

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Deficiency of the DNA damage repair (DDR) signaling pathways is potentially responsible for genetic instability and oncogenesis in tumors, including colorectal cancer. However, the correlations of mutated DDR signaling pathways to the prognosis of colorectal cancer liver metastasis (CRLM) after resection and other clinical applications have not been fully investigated. Here, to test the potential correlation of mutated DDR pathways with survival and pre-operative chemotherapy responses, tumor tissues from 146 patients with CRLM were collected for next-generation sequencing with a 620-gene panel, including 68 genes in 7 DDR pathways, and clinical data were collected accordingly. The analyses revealed that 137 of 146 (93.8%) patients had at least one mutation in the DDR pathways. Mutations in BER, FA, HRR and MMR pathways were significantly correlated with worse overall survival than the wild-types (P < 0.05), and co-mutated DDR pathways showed even more significant correlations (P < 0.01). The number of mutated DDR pathways was also proved an independent stratifying factor of overall survival by Cox multivariable analysis with other clinical factors and biomarkers (hazard ratio = 9.14; 95% confidence interval, 1.21–68.9; P = 0.032). Additionally, mutated FA and MMR pathways were positively and negatively correlated with the response of oxaliplatin-based pre-operative chemotherapy (P = 0.0095 and 0.048, respectively). Mutated DDR signaling pathways can predict pre-operative chemotherapy response and post-operative survival in CRLM patients.

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The somatic mutation landscape of Chinese Colorectal Cancer

Cited by 20 publications

References 46 publications

A bioinformatic analysis: the overexpression and clinical significance of FCGBP in ovarian cancer

A bioinformatic analysis: the overexpression and clinical significance of FCGBP in ovarian cancer

IgG Fc Binding Protein (FCGBP) is Down-Regulated in Metastatic Lesions and Predicts Survival in Metastatic Colorectal Cancer Patients

Mutated DNA Damage Repair Pathways Are Prognostic and Chemosensitivity Markers for Resected Colorectal Cancer Liver Metastases

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