scholarly journals Comprehensive analysis of immune related lncRNAs in the tumor microenvironment of stage II–III colorectal cancer

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Zan Zhang ◽  
Yixin Wu ◽  
Changyuan Yu ◽  
Zhengtai Li ◽  
Lida Xu
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Comprehensive Analysis ◽  
Stage Ii

Genome-wide analysis indicating cancer associated fibroblast (CAF) impacts on colorectal cancer (CRC) prognosis via immunosuppression.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3543-3543
Author(s):  
Yu-feng Chen ◽  
Xiaojian Wu ◽  
Feng Gao
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Adjuvant Chemotherapy ◽  
Tumor Microenvironment ◽  
Prognostic Value ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Stage Ii ◽  
Training Cohort ◽  
Cancer Associated Fibroblast

3543 Background: Cancer associated fibroblast (CAF) in tumor microenvironment is associated with poor prognosis and chemo-resistance in multiple solid tumors, however, there is lack of universal measure of CAF in colorectal cancer (CRC). The aim of this study was to assess fibroblast-signature for predicting outcome and analyze relevant mechanism. Methods: A dataset including 316 CRC patients without adjuvant chemotherapy was used as the discovery cohort for the identification of prognostic fibroblast-related genes (FRGs). A total of 1,352 CRC patients were then divided into one training cohort (n = 461) and two validation cohorts (n = 338, n = 553, respectively) for the construction of fibroblast-related gene signature (FRGS) and the verification of its prognostic value in stage II/III CRC patients. Functional annotation and analysis were performed to reveal the relevant mechanism. Results: A 11-gene signature was derived, which was prognostic for stage II/III CRC patients in two validation cohort (Validation-1 cohort: HR = 1.90, 95%CI = 1.16-3.12, P< 0.01; Validation-2 cohort: HR = 1.95, 95%CI = 1.39-2.73, P< 0.001). High CAF risk was correlated with worse prognosis in CRC patients without adjuvant chemotherapy (HR = 3.63, 95%CI = 2.24-5.88, P< 0.001), but not in patients who received adjuvant chemotherapy ( P= 0.154). Similar trends were found in Validation-1 cohort. After integrated with clinical characteristics, FRGS was confirmed as an independent prognostic factor after adjusted for TNM stage of tumor in multivariate analysis (Training cohort: HR = 3.19, 95%CI = 1.88-5.41, P< 0.001; Validation-1 cohort: HR = 5.00, 95%CI = 1.58-15.85, P= 0.007; Validation-2 cohort: HR = 2.99, 95%CI = 1.44-6.21, P= 0.003). Furthermore, enrichment analysis found that anti-tumor immune response was suppressed in the high CAF risk group. Conclusions: The 11-gene FRGS had independent prognostic value for CRC patients, as well as in prediction of benefit from chemotherapy. CAF in tumor microenvironment might impact on the prognosis of CRC patients via inhibiting immune response.

The clinical utility of a tumour microenvironment-based histopathological score in patients with primary operable colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 664-664
Author(s):  
James Hugh Park ◽  
Donald C. Mcmillan ◽  
Paul G. Horgan ◽  
Campbell S.D. Roxburgh
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Clinical Utility ◽  
Prognostic Score ◽  
Tumor Stroma ◽  
Stage Ii ◽  
Stage Iii ◽  
Inflammatory Cell Infiltrate ◽  
Cancer Specific Survival ◽  
Cumulative Score

664 Background: The tumor microenvironment is increasingly recognized as an important determinant of disease progression and outcome in colorectal cancer (CRC). The aim of the present study was to examine the clinical utility of a novel histopathological prognostic score based on both the tumor inflammatory cell infiltrate and the tumor stroma percentage, termed the Glasgow Microenvironment Score (GMS), in patients with primary operable CRC. Methods: Using routine H&E pathological sections, Klintrup-Mäkinen (KM) grade was graded as strong or weak, and tumor stroma percentage (TSP) was assessed as high (>50%) or low (≤50%) retrospectively in 319 patients undergoing resection of stage II-III CRC. The relationship between a cumulative score based on these factors and cancer-specific survival (CSS) was examined. Results: Median survival of survivors was 122 months with 106 cancer deaths. 63% of patients had stage II CRC. 5-year CSS of patients with stage II and stage III CRC was 82% and 58% respectively (p<0.001). 33% of patients were GMS=0 (strong KM/high or low TSP), 47% were GMS=1 (weak KM/low TSP), and 20% GMS=2 (weak KM/high TSP), with 5-year CSS of 86%, 74%, and 48% (p<0.001) respectively. On multivariate analysis, GMS was associated with CSS (HR 1.77, p<0.001), independent of age, emergency presentation, TNM stage and venous invasion (all p<0.01), and peritoneal involvement (p<0.05). The combination of TNM and GMS stratified 5-year CSS from 92% (stage II, GMS=0) to 35% (stage III, GMS=2) (Table). Conclusions: The present study shows the clinical utility of a novel, routinely available assessment of the tumor microenvironment in patients undergoing curative resection of CRC. [Table: see text]

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

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.

Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer

2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Risk Predictor

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

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

scholarly journals HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mahdi Golkaram ◽  
Michael L. Salmans ◽  
Shannon Kaplan ◽  
Raakhee Vijayaraghavan ◽  
Marta Martins ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Subtype ◽  
Endogenous Retroviruses ◽  
Stage Ii ◽  
Clinicopathological Factors ◽  
Whole Exome ◽  
Potential Biomarker ◽  
Whole Transcriptome Sequencing ◽  
Next Generation Sequencing Ngs ◽  
Herv Expression

AbstractColorectal cancer (CRC) is one of the most lethal malignancies. The extreme heterogeneity in survival rate is driving the need for new prognostic biomarkers. Human endogenous retroviruses (hERVs) have been suggested to influence tumor progression, oncogenesis and elicit an immune response. We examined multiple next-generation sequencing (NGS)-derived biomarkers in 114 CRC patients with paired whole-exome and whole-transcriptome sequencing (WES and WTS, respectively). First, we demonstrate that the median expression of hERVs can serve as a potential biomarker for prognosis, relapse, and resistance to chemotherapy in stage II and III CRC. We show that hERV expression and CD8+ tumor-infiltrating T-lymphocytes (TILs) synergistically stratify overall and relapse-free survival (OS and RFS): the median OS of the CD8-/hERV+ subgroup was 29.8 months compared with 37.5 months for other subgroups (HR = 4.4, log-rank P < 0.001). Combing NGS-based biomarkers (hERV/CD8 status) with clinicopathological factors provided a better prediction of patient survival compared to clinicopathological factors alone. Moreover, we explored the association between genomic and transcriptomic features of tumors with high hERV expression and establish this subtype as distinct from previously described consensus molecular subtypes of CRC. Overall, our results underscore a previously unknown role for hERVs in leading to a more aggressive subtype of CRC.

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