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

PLoS ONE ◽  
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.

scholarly journals Identification of EMT-related high-risk stage II colorectal cancer and characterisation of metastasis-related genes

2020 ◽  
Vol 123 (3) ◽  
pp. 410-417 ◽  
Author(s):  
Kai Wang ◽  
Kai Song ◽  
Zhigang Ma ◽  
Yang Yao ◽  
Chao Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Gene Pair ◽  
Stage Ii ◽  
Related Gene ◽  
Prognostic Signature ◽  
Mesenchymal Transition ◽  
Relapse Risk ◽  
Gene Pairs ◽  
Stage Ii Colorectal Cancer

Abstract Background Our laboratory previously reported an individual-level prognostic signature for patients with stage II colorectal cancer (CRC). However, this signature was not applicable for RNA-sequencing datasets. In this study, we constructed a robust epithelial-to-mesenchymal transition (EMT)- related gene pair prognostic signature. Methods Based on EMT-related genes, metastasis-associated gene pairs were identified between metastatic and non-metastatic samples. Then, we selected prognosis-associated gene pairs, which were significantly correlated with disease-free survival of stage II CRC using multivariate Cox regression model, as the EMT-related prognosis signature. Results An EMT-related signature composed of fifty-one gene pairs (51-GPS) for prediction-relapse risk of patients with stage II CRC was developed, whose prognostic efficiency was validated in independent datasets. Moreover, 51-GPS achieved better predictive performance than other reported signatures, including a commercial signature Oncotype Dx colon cancer and an immune-related gene pair signature. Besides, EMT-related functional gene sets achieved high enrichment scores in high-risk samples. Especially, loss-of-function antisense approach showed that DEGs between the predicted two clusters were metastasis-related. Conclusions The EMT-related gene pair signature can identify the high relapse-risk patients with stage II CRC, which can facilitate individualised management of patients.

scholarly journals KRT17 as a prognostic biomarker for stage II colorectal cancer

2019 ◽  
Vol 41 (5) ◽  
pp. 591-599 ◽  
Author(s):  
Daisuke Ujiie ◽  
Hirokazu Okayama ◽  
Katsuharu Saito ◽  
Mai Ashizawa ◽  
Aung Kyi Thar Min ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Prognostic Biomarker ◽  
Clinicopathological Features ◽  
Stage Ii ◽  
Positive Staining ◽  
Prognostic Impact ◽  
Rna Seq ◽  
Total N ◽  
Stage Ii Colorectal Cancer

Abstract Adjuvant chemotherapy is considered for patients with stage II colorectal cancer (CRC) characterized by poor prognostic clinicopathological features; however, current stratification algorithms remain inadequate for identifying high-risk patients. To develop prognostic assays, we conducted a step-wise screening and validation strategy using nine cohorts of stage II patients based on multiple platforms, including microarray, RNA-sequencing (RNA-seq) and immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) tissues. Four microarray datasets (total n = 458) were used as the discovery set to screen for single genes associated with postoperative recurrence. Prognostic values of candidate genes were evaluated in three independent microarray/RNA-seq validation cohorts (n = 89, n = 93 and n = 183, respectively), and then IHC for KRT17 was conducted in two independent FFPE series (n = 110 and n = 44, respectively). We found that high levels of KRT17 transcript expression were significantly associated with poor relapse-free survival (RFS) not only in the discovery set, but also in three validation cohorts, and its prognostic impact was independent of conventional factors by multivariate analyses. Positive staining of KRT17 protein was significantly associated with poor RFS in two independent FFPE cohorts. KRT17 protein expression had independent prognostic impact on RFS in a multivariate model adjusted for conventional variables, including high-risk clinicopathological features. In conclusion, using nine independent cohorts consisting of 997 stage II patients, we identified and validated the expression of KRT17 transcript and KRT17 protein as a robust prognostic biomarker that can discriminate postoperative stage II patients who are at high probability of disease recurrence, providing additional prognostic stratification beyond the currently available high-risk factors.

scholarly journals Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients

2018 ◽  
Vol 47 (2) ◽  
pp. 630-640 ◽  
Author(s):  
Xiang Hu ◽  
Ya-Qi Li ◽  
Qing-Guo Li ◽  
Yan-Lei Ma ◽  
Jun-Jie Peng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factor ◽  
High Risk ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Stage Ii ◽  
Prognostic Impact ◽  
Mucinous Histology ◽  
High Risk Factor ◽  
Colorectal Cancer Patients

Background/Aims: Colorectal mucinous adenocarcinoma (MA) has been associated with a worse prognosis than adenocarcinoma (AD) in advanced stages. Little is known about the prognostic impact of a mucinous histotype on the early stages of colorectal cancer with negative lymph node (LN) metastasis. In contrast to the established prognostic factors such as T stage and grading, the histological subtype is not thought to contribute to the therapeutic outcome, although different subtypes can potentially represent different entities. In this study, we aimed to define the prognostic value of mucinous histology in colorectal cancer with negative LNs. Methods: Between 2006 and 2017, a total of 4893 consecutive patients without LN metastasis underwent radical surgery for primary colorectal cancer (MA and AD) in Fudan University Shanghai Cancer Center (FUSCC). Clinical, histopathological, and survival data were analyzed. Results: The incidence of MA was 11% in 4893 colorectal cancer patients without LN metastasis. The MA patients had a higher T category, a greater percentage of LN harvested, larger tumor size and worse grading than the AD patients (p < 0.001 for each). We found that MA histology was correlated with a poor prognosis in terms of relapse in node-negative patients, and MA histology combined with TNM staging may be a feasible method for predicting the relapse rate. Additionally, MA presented as a high-risk factor in patients with negative perineural or vascular invasion and well/moderate-differentiation and showed a more dismal prognosis for stage II patients. Meanwhile, the disease-free survival was identical in MA and AD patients after neo- and adjuvant chemotherapy. Conclusion: MA histology is an independent predictor of poor prognosis due to relapse in LN-negative colorectal cancer patients. Mucinous histology can suggest a possible high risk in early-stage colorectal carcinoma.

The efficacy of adjuvant chemotherapy for resected high-risk stage II and stage III colorectal cancer in frail patients

2021 ◽  
Author(s):  
Kosuke Mima ◽  
Nobutomo Miyanari ◽  
Keisuke Kosumi ◽  
Takuya Tajiri ◽  
Kosuke Kanemitsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Stage Iii ◽  
Frail Patients

Identification of a lncRNA prognostic signature-related to stem cell index and its significance in colorectal cancer

2021 ◽  
Author(s):  
Xiao-Cheng Wang ◽  
Ya Liu ◽  
Fei-Wu Long ◽  
Liang-Ren Liu ◽  
Chuan-Wen Fan
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Markers ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Free Survival ◽  
Cancer Genome Atlas ◽  
Bioinformatic Approaches ◽  
Cell Phenotypes ◽  
The Relationship

Background: The relationship between long noncoding RNAs (lncRNAs) and the mRNA stemness index (mRNAsi) in colorectal cancer (CRC) is still unclear. Materials & methods: The mRNAsi, mRNAsi-related lncRNAs and their clinical significance were analyzed by bioinformatic approaches in The Cancer Genome Atlas (TCGA)-COREAD dataset. Results: mRNAsi was negatively related to pathological features but positively related to overall survival and recurrence-free survival in CRC. A five mRNAsi-related lncRNAs prognostic signature was further developed and showed independent prognostic factors related to overall survival in CRC patients, due to the five mRNAsi-related lncRNAs involved in several pathways of the cancer stem cells and malignant cancer cell phenotypes. Conclusion: The present study highlights the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers.

scholarly journals A symptom-based model to predict colorectal cancer in low-resource countries: Results from a prospective study of patients at high risk for colorectal cancer

Cancer ◽  
2018 ◽  
Vol 124 (13) ◽  
pp. 2766-2773 ◽  
Author(s):  
Olusegun Isaac Alatise ◽  
Omobolaji O. Ayandipo ◽  
Ademola Adeyeye ◽  
Ken Seier ◽  
Akinwunmi O. Komolafe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Prospective Study ◽  
Low Resource ◽  
A Prospective Study

Prognostic impact of interhospital variation in adjuvant chemotherapy for patients with Stage II/III colorectal cancer: a nationwide study

2018 ◽  
Vol 20 (7) ◽  
pp. O162-O172 ◽  
Author(s):  
K. Arakawa ◽  
K. Kawai ◽  
T. Tanaka ◽  
K. Hata ◽  
K. Sugihara ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Prognostic Impact ◽  
Nationwide Study

Mucinous Adenocarcinoma as a High-risk Factor in Stage II Colorectal Cancer: A Propensity Score-matched Study from Japan

2020 ◽  
Vol 40 (3) ◽  
pp. 1651-1659 ◽  
Author(s):  
LIMING WANG ◽  
YASUMITSU HIRANO ◽  
GREGORY HENG ◽  
TOSHIMASA ISHII ◽  
HIROKA KONDO ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factor ◽  
High Risk ◽  
Propensity Score ◽  
Mucinous Adenocarcinoma ◽  
Stage Ii ◽  
High Risk Factor ◽  
Stage Ii Colorectal Cancer ◽  
Matched Study

scholarly journals Prognostic Impact of the Number of Examined Lymph Nodes in Stage II Colorectal Adenocarcinoma: A Retrospective Study

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Purun Lei ◽  
Ying Ruan ◽  
Jianpei Liu ◽  
Qixian Zhang ◽  
Xiao Tang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Stage Ii ◽  
Lymph Node Status ◽  
Stage Migration ◽  
Prognostic Impact ◽  
Disease Specific Survival ◽  
Stage Ii Colorectal Cancer ◽  
Disease Specific

Background. Evaluation of lymph node status is critical in colorectal carcinoma (CRC) treatment. However, as patients with node involvement may be incorrectly classified into earlier stages if the examined lymph node (ELN) number is too small and escape adjuvant therapy, especially for stage II CRC. The aims of this study were to assess the impact of the ELN on the survival of patients with stage II colorectal cancer and to determine the optimal number. Methods. Data from the US Surveillance, Epidemiology, and End Results (SEER) database on stage II resected CRC (1988-2013) were extracted for mathematical modeling as ELN was available since 1988. Relationship between ELN count and stage migration and disease-specific survival was analyzed by using multivariable models. The series of the mean positive LNs, odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS (Locally Weighted Scatterplot Smoothing) smoother, and the structural break points were determined by the Chow test. An independent cohort of cases from 2014 was retrieved for validation in 5-year disease-specific survival (DSS). Results. An increased ELN count was associated with a higher possibility of metastasis LN detection (OR 1.010, CI 1.009-1.011, p<0.001) and better DSS in LN negative patients (OR 0.976, CI 0.975-0.977, p<0.001). The cut-off point analysis showed a threshold ELN count of 21 nodes (HR 0.692, CI 0.667-0.719, p<0.001) and was validated with significantly better DSS in the SEER 2009 cohort CRC (OR 0.657, CI 0.522-0.827, p<0.001). The cut-off value of the ELN count in site-specific surgeries was analyzed as 20 nodes in the right hemicolectomy (HR 0.674, CI 0.638-0.713, p<0.001), 19 nodes in left hemicolectomy (HR 0.691, CI 0.639-0.749, p<0.001), and 20 nodes in rectal resection patients (HR 0.671, CI 0.604-0.746, p<0.001), respectively. Conclusions. A higher number of ELNs are associated with more-accurate node staging and better prognosis in stage II CRCs. We recommend that at least 21 lymph nodes be examined for accurate diagnosis of stage II colorectal cancer.

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