Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases

Fassan, Matteo; Vianello, Luca; Sacchi, Diana; Fanelli, Giuseppe Nicolò; Munari, Giada; Scarpa, Marco; Cappellesso, Rocco; Loupakis, Fotios; Lanza, Cristiano; Salmaso, Roberta; Mescoli, Claudia; Valeri, Nicola; Agostini, Marco; D’Angelo, Edoardo; Pucciarelli, Salvatore; Veronese, Nicola; Luchini, Claudio

doi:10.1186/s12935-018-0634-8

Cited by 7 publications

(6 citation statements)

References 39 publications

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“…BRAF-mutated (BRAFmt) CRCs have specific clinicopathological and molecular features [14][15][16][17][18], identifying a distinct subset with aggressive phenotype and poor outcome ( Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

The heterogeneous clinical and pathological landscapes of metastatic Braf-mutated colorectal cancer

et al. 2020

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Colorectal cancer (CRC) is a complex and molecularly heterogeneous disease representing one of the most frequent causes of cancer-related death worldwide. About 8-15% of CRCs harbor a mutation in BRAF gene, a proto-oncogene involved in cell proliferation, differentiation and survival through the MAPK signaling cascade. The acquisition of BRAF mutation is an early event in the "serrated" CRC carcinogenetic pathway and is associated with specific and aggressive clinico-pathological and molecular features. Despite that the presence of BRAF mutation is a well-recognized negative prognostic biomarker in metastatic CRC (mCRC), a great heterogeneity in survival outcome characterizes these patients, due to the complex, and still not completely fully elucidated, interactions between the clinical, genetic and epigenetic landscape of BRAF mutations. Because of the great aggressiveness of BRAF-mutated mCRCs, only 60% of patients can receive a second-line chemotherapy; so intensive combined and tailored first-line approach could be a potentially effective strategy, but to minimize the selective pressure of resistant clones and to reduce side effects, a better stratification of patients bearing BRAF mutations is needed.

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Section: Introductionmentioning

confidence: 99%

The heterogeneous clinical and pathological landscapes of metastatic Braf-mutated colorectal cancer

et al. 2020

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“…Despite some techniques like MRI texture analysis or phenotype determinations that have been introduced to roughly assess the TDs status, an accurate prediction shaping personalized TDs features remains an arduous task. [31][32][33][34] A predictive nomogram is currently an efficient tool to improve preoperative TDs prediction and investigate related mechanisms. Our nomogram incorporated six-gene risk score system (miR-614, miR-1197, miR-4770, miR-3136, miR-3173, and miR-4636) and exhibited satisfactory performances in high-risk group identification.…”

Section: Discussionmentioning

confidence: 99%

A Six-microRNA Signature Nomogram for Preoperative Prediction of Tumor Deposits in Colorectal Cancer

Xiao

Guo

Zhang

et al. 2022

IJGM

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Purpose Tumor deposits (TDs) are acknowledged negative prognostic factors in colorectal cancer (CRC), and their pathogenesis remains a puzzle. This study aimed to construct and validate a nomogram available for preoperative TDs prediction in CRC patients. Patients and Methods Patients from the Surveillance, Epidemiology, and End Results (SEER) and the cancer genome atlas (TCGA) databases were randomly divided into training and validation sets according to the sample size ratio of 7:3. Univariate logistic regression was performed for identifying differentially expressed microRNAs between TDs and non-TDs. Nomograms for TDs prediction were developed from the multivariate logistic regression model with least absolute shrinkage and selection operator and were validated internally in terms of accuracy, calibration, and clinical utility. Based on the target genes, pathways tightly associated with TDs were selected using enrichment analysis. Results Six clinicopathologic factors and expressions of six microRNAs (miR-614, miR-1197, miR-4770, miR-3136, miR-3173, and miR-4636) differed significantly between TDs and non-TDs CRC patients from the SEER and TCGA training sets. We compared potential prediction discrimination between two nomograms: a clinicopathologic nomogram and a six-microRNA signature nomogram. The six-microRNA signature nomogram revealed better accuracy than the clinicopathologic one for TDs prediction (AUC values of 0.96 and 0.93 in the validation cohort). The calibration plots and decision curve analysis demonstrated that the six-microRNA signature nomogram had better validity and a greater prognostic benefit versus the clinicopathologic one for TDs prediction. Calcium signaling pathways were closely associated with roles of the six microRNAs in TDs of CRC patients. Conclusion The six-microRNA signature nomogram can be used as an efficient tool for preoperative TDs prediction in CRC patients.

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“…There is no final conclusion about the effect of the number of cancer nodules on prognosis. Studies have shown that the count of CD8-positive T lymphocytes in cancer nodules of patients with CRC is significantly higher than that of tumor tissue, 28 suggesting that changes in the tumor microenvironment are important for the generation of cancer nodules. The dMMR status has an important effect on the tumor microenvironment, 29 suggesting that the generation of cancer nodules may be related to the microsatellite status.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Clinicopathological Characteristics of Stage I–III Colorectal Cancer Patients Deficient in Mismatch Repair Proteins

Yue

Cai

et al. 2021

OTT

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Purpose To investigate the clinicopathological characteristics of stage I–III colorectal cancer (CRC) patients with deficient mismatch repair (dMMR) protein. Patients and Methods A retrospective analysis of 61 patients with stage I–III CRC confirmed by immunohistochemistry as dMMR after radical resection at Shenjing Hospital of China Medical University from May 2017 to June 2019 was performed. A total of 183 stage I–III CRC patients with proficient mismatch repair (pMMR) protein from the same period were randomly selected as a control group. The clinicopathological data of the two groups were investigated. Results There were significant differences between the two groups in age, sex, site of onset, maximum diameter of tumor, T stage, tumor differentiation, and histological type ( P < 0.05). No significant difference was detected in nerve vessel invasion, cancer nodules, the N stage or the TNM stage. In the dMMR group, 41 patients (66.13%) showed PMS2/MLH1 deletion, and the number of MSH2/MSH6 deletion is 21 patients (33.87%). Among them, 34 patients (54.84%) had PMS2 and MLH1 deficiency. In total, 16 patients (25.81%) had MSH2 and MSH6 deficiency. A total of 5 patients (8.06%) showed simply PMS2 deletion and 5 patients (8.06%) showed simply MSH6 deletion. In total, 2 patients (3.23%) showed concurrent loss of PMS2, MLH1 and MSH2. No significant difference were found ( P > 0.05) in the above factors among dMMR CRC patients with different MMR proteins deletions. Conclusion Our results show that dMMR status may be more likely exist in female and younger (≤55 years) patients with a greater tumor burden (>5cm), right colon, T4 stage disease, poor differentiation and mucinous adenocarcinoma. Loss of PMS2 and MLH1 is the most common pattern of MMR protein expression deficiency, followed by concurrent deletion of MSH2 and MSH6.

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Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases

Cited by 7 publications

References 39 publications

The heterogeneous clinical and pathological landscapes of metastatic Braf-mutated colorectal cancer

The heterogeneous clinical and pathological landscapes of metastatic Braf-mutated colorectal cancer

A Six-microRNA Signature Nomogram for Preoperative Prediction of Tumor Deposits in Colorectal Cancer

Analysis of the Clinicopathological Characteristics of Stage I–III Colorectal Cancer Patients Deficient in Mismatch Repair Proteins

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