Genome-wide Discovery and Identification of a Novel miRNA Signature for Recurrence Prediction in Stage II and III Colorectal Cancer

Background: Hypoxia is associated with a poorer clinical outcome and resistance to chemotherapy in solid tumors; identifying hypoxic-related colorectal cancer (CRC) and revealing its mechanism are important. The aim of this study was to assess hypoxia signature for predicting prognosis and analyze relevant mechanism.Methods: Patients without chemotherapy were selected for the identification of hypoxia-related genes (HRGs). A total of six independent datasets that included 1,877 CRC patients were divided into a training cohort and two validation cohorts. Functional annotation and analysis were performed to reveal relevant mechanism.Results: A 12-gene signature was derived, which was prognostic for stage II/III CRC patients in two validation cohorts [TCGA, n = 509, hazard ratio (HR) = 2.14, 95% confidence interval (CI) = 1.18 – 3.89, P = 0.01; metavalidation, n = 590, HR = 2.46, 95% CI = 1.59 – 3.81, P < 0.001]. High hypoxic risk was correlated with worse prognosis in CRC patients without adjuvant chemotherapy (HR = 5.1, 95% CI = 2.51 – 10.35, P < 0.001). After integration with clinical characteristics, hypoxia-related gene signature (HRGS) remained as an independent prognostic factor in multivariate analysis. Furthermore, enrichment analysis found that antitumor immune response was suppressed in the high hypoxic group.Conclusions: HRGS is a promising system for estimating disease-free survival of stage II/III CRC patients. Hypoxia tumor microenvironment may be via inhibiting immune response to promote chemoresistance in stage II/III CRC patients.

Download Full-text

Development and validation of a novel miRNA classifier as a prognostic signature for stage II/III colorectal cancer

Annals of Translational Medicine ◽

10.21037/atm-20-1751 ◽

2021 ◽

Vol 9 (9) ◽

pp. 747-747

Author(s):

Junlan Feng ◽

Qing Wei ◽

Muqing Yang ◽

Xiaodong Wang ◽

Bin Liu ◽

...

Keyword(s):

Colorectal Cancer ◽

Stage Ii ◽

Prognostic Signature ◽

Novel Mirna ◽

Development And Validation

Download Full-text

Establishment and Validation of a Novel Promising Recurrence Prediction Molecular Subtype Classification for Patients with Stage II Colorectal Cancer

SSRN Electronic Journal ◽

10.2139/ssrn.3909727 ◽

2021 ◽

Author(s):

Zheng Jiang ◽

Ran Wei ◽

Dechao Bu ◽

Shuofeng Li ◽

Guanhua Yu ◽

...

Keyword(s):

Colorectal Cancer ◽

Molecular Subtype ◽

Stage Ii ◽

Subtype Classification ◽

Recurrence Prediction ◽

Stage Ii Colorectal Cancer

Download Full-text

Abstract 5721: Genome-wide discovery and identification of a novel microrna signature for recurrence prediction in colorectal cancer

10.1158/1538-7445.am2017-5721 ◽

2017 ◽

Author(s):

Raju Kandimalla ◽

Feng Gao ◽

Naoki Takahashi ◽

Yasuhide Yamada ◽

Takatoshi Matsuyama ◽

...

Keyword(s):

Colorectal Cancer ◽

Genome Wide ◽

Recurrence Prediction

Download Full-text

Transcriptomic profiling of adjuvant colorectal cancer identifies three key prognostic biological processes and a disease specific role for granzyme B

PLoS ONE ◽

10.1371/journal.pone.0262198 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0262198

Author(s):

Anneleen Daemen ◽

Akshata R. Udyavar ◽

Thomas Sandmann ◽

Congfen Li ◽

Linda J. W. Bosch ◽

...

Keyword(s):

Colorectal Cancer ◽

High Risk ◽

Granzyme B ◽

The Cancer Genome Atlas ◽

Stage Ii ◽

Prognostic Impact ◽

Prognostic Signature ◽

Recurrence Prediction ◽

Context Specific ◽

A Prospective Study

Background Colorectal cancer (CRC) is a leading cause of cancer-related deaths, with a 5% 5-year survival rate for metastatic disease, yet with limited therapeutic advancements due to insufficient understanding of and inability to accurately capture high-risk CRC patients who are most likely to recur. We aimed to improve high-risk classification by identifying biological pathways associated with outcome in adjuvant stage II/III CRC. Methods and findings We included 1062 patients with stage III or high-risk stage II colon carcinoma from the prospective three-arm randomized phase 3 AVANT trial, and performed expression profiling to identify a prognostic signature. Data from validation cohort GSE39582, The Cancer Genome Atlas, and cell lines were used to further validate the prognostic biology. Our retrospective analysis of the adjuvant AVANT trial uncovered a prognostic signature capturing three biological functions—stromal, proliferative and immune—that outperformed the Consensus Molecular Subtypes (CMS) and recurrence prediction signatures like Oncotype Dx in an independent cohort. Importantly, within the immune component, high granzyme B (GZMB) expression had a significant prognostic impact while other individual T-effector genes were less or not prognostic. In addition, we found GZMB to be endogenously expressed in CMS2 tumor cells and to be prognostic in a T cell independent fashion. A limitation of our study is that these results, although robust and derived from a large dataset, still need to be clinically validated in a prospective study. Conclusions This work furthers our understanding of the underlying biology that propagates stage II/III CRC disease progression and provides scientific rationale for future high-risk stratification and targeted treatment evaluation in biomarker defined subpopulations of resectable high-risk CRC. Our results also shed light on an alternative GZMB source with context-specific implications on the disease’s unique biology.

Download Full-text

CT Monitoring Cuts Mortality in Stage II, III Colorectal Cancer

Internal Medicine News ◽

10.1016/s1097-8690(05)72418-5 ◽

2005 ◽

Vol 38 (23) ◽

pp. 4

Author(s):

MARY ANN MOON

Keyword(s):

Colorectal Cancer ◽

Stage Ii

Download Full-text

INVESTIGATION KRAS MUTATION IN CIRCULATION TUMOR DNA IN DIFFERENT STAGES OF COLORECTAL CANCER

Problems in oncology ◽

10.37469/0507-3758-2019-65-5-701-707 ◽

2019 ◽

Vol 65 (5) ◽

pp. 701-707

Author(s):

Vitaliy Shubin ◽

Yuriy Shelygin ◽

Sergey Achkasov ◽

Yevgeniy Rybakov ◽

Aleksey Ponomarenko ◽

...

Keyword(s):

Colorectal Cancer ◽

Plasma Volume ◽

Kras Mutation ◽

Stage Iv ◽

Circulating Tumor Dna ◽

Stage Ii ◽

Kras Gene ◽

Kras Mutations ◽

Droplet Pcr ◽

Tumor Dna

To determine mutations in the plasma KRAS gene in patients with colorectal cancer was the aim of this study. The material was obtained from 44 patients with colorectal cancer of different stages (T1-4N0-2bM0-1c). Plasma for the presence of KRAS gene mutation in circulating tumor DNA was investigated using digital droplet polymerase chain reaction (PCR). KRAS mutations in circulating tumor DNA isolated from 1 ml of plasma were detected in 13 (30%) patients with cancer of different stages. Of these, with stage II, there were 3 patients, with III - 5 and with IV - 5. Patients who did not have mutations in 1 ml of plasma were analyzed for mutations of KRAS in circulating tumor DNA isolated from 3 ml of plasma. Five more patients with KRAS mutations were found with II and III stages. The highest concentrations of circulating tumor DNA with KRAS mutation were found in patients with stage IV. The increase in plasma volume to 3 ml did not lead to the identification of mutations in I stage. This study showed that digital droplet PCR allows identification of circulating tumor DNA with the KRAS mutations in patients with stage II-IV of colon cancer. The results can be used to determine the degree of aggressiveness of the tumor at different stages of the disease, but not the 1st, and it is recommended to use a plasma volume of at least 3 ml.

Download Full-text