Microsatellite instability, disease-free survival and role of tumour infiltrating lymphocytes (Invited editorial on ‘Predictors of disease-free survival in colorectal cancer with microsatellite instability: An AGEO multicenter study’)

2015 ◽  
Vol 51 (8) ◽  
pp. 922-924 ◽  
Author(s):  
Henry T. Lynch ◽  
Stephen J. Lanspa ◽  
Carrie L. Snyder ◽  
Kristen M. Drescher
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Multicenter Study ◽  
Disease Free Survival ◽  
Free Survival ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes ◽  
Disease Free

scholarly journals STIL-a novel link in Shh and Wnt signaling, endowing oncogenic and stem like attributes to colorectal cancer

2020 ◽  
Author(s):  
Tapas Pradhan ◽  
Vikas Kumar ◽  
H Evangeline Surya ◽  
R Krishna ◽  
Samu John ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Importance ◽  
Disease Free Survival ◽  
Drug Resistant ◽  
Free Survival ◽  
Over Expression ◽  
Disease Free

AbstractDiscovery of potent gene regulating tumorigenesis and drug resistance is of high clinical importance. STIL is an oncogene, however its molecular insights and role in colorectal oncogenesis are unknown. In this study we have explored role of STIL in tumorigenesis and studied its molecular targets in colorectal cancer (CRC). STIL silencing reduced proliferation and tumor growth in CRC. Further, STIL was found to regulate stemness markers CD133 & CD44 and drug resistant markers Thymidylate synthase, ABCB1 & ABCG2 both in in-vitro and in-vivo CRC models. In addition, over expression of STIL mRNA was found to be associated with reduced disease free survival in CRC cases. To our surprise we observed an Shh independent regulation of stemness and drug resistant genes mediated by STIL. Interestingly, we found an Shh independent regulation of β-catenin mediated by STIL via p-AKT, which partially answers Shh independent regulatory mechanism of CSC markers by STIL. Our study suggest an instrumental role of STIL in molecular manifestation of CRC and progression.

MicroRNAs for Diagnosis and Treatment of Colorectal Cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Haitao Mei ◽  
Yugang Wen
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Diagnosis And Treatment ◽  
High Morbidity ◽  
Circulating Micrornas ◽  
Free Survival ◽  
The Past ◽  
Common Cancer ◽  
Disease Free

: Colorectal cancer (CRC) is the third most common cancer worldwide, with high morbidity and mortality rates. The diagnosis and treatment of CRC have the most significant value for disease-free survival. Early diagnosis and early surgical resection are generally considered to be the most effective ways to reduce CRC mortality. In the past few years, many researchers have focused on the role of microRNAs in different tumors, making the functions of microRNAs gradually clear. The present study reviews the role of microRNAs in the diagnosis and treatment of colorectal cancer. Compared with the usual diagnosis methods and biomarker, circulating microRNAs can be promising new effective biomarkers for CRCdiagnosis and treatment.

scholarly journals Prognostic and Immunological Role of THBS2 in Colorectal cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Bin Deng ◽  
Xiu-Ping Liu ◽  
Xiong Wang
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Bioinformatic Analysis ◽  
Histological Subtype ◽  
Free Survival ◽  
Immune Infiltration ◽  
Prognostic Analysis ◽  
Functional Mechanisms ◽  
Disease Free

Objective. Thrombospondin 2 (THBS2) acts as oncogenic or tumor suppressive gene in diverse cancers. Here we studied the prognostic and immunological role of THBS2 in colorectal cancer (CRC) using bioinformatic analysis. Methods. The genetic and protein expression of THBS2 in CRC were explored across several databases, including ONCOMINE, GEPIA2, TIMER 2.0, UALCAN and HPA databases. Correlation between THBS2 expression and clinical features in CRC was assessed using UALCAN tool. Prognostic analysis was performed using GEPIA2 and PrognoScan. Immune infiltration correlation with THBS2 in CRC was investigated with TIMER 2.0 and TISIDB. THBS2 binding and correlated genes were analyzed using String, GEPIA2, and TIMER 2.0. Results. THBS2 was significantly higher in CRC across multiple databases. Age and histological subtype were correlated with THBS2 level. High THBS2 expression correlated with short overall and disease-free survival. THBS2 expression was positively correlated with immune infiltrates in CRC. Moreover, extracellular matrix structural constituent and organization, PI3K-Akt pathway, were involved in the functional mechanisms of THBS2. Conclusions. THBS2 correlates with poor prognosis and immune infiltration in CRC. THBS2 may act as a prognostic and immunological biomarker for CRC.

scholarly journals INFLUENCE OF SOMATIC MUTATIONS OF KRAS, NRAS, BRAF AND MICROSATELLITE INSTABILITY STATUS ON SURVIVAL OF COLORECTAL CANCER PATIENTS WITH PERITONAL CARCINO

2020 ◽  
Vol 19 (5) ◽  
pp. 61-67
Author(s):  
V. P. Shubin ◽  
Yu. A. Shelygin ◽  
S. I. Achkasov ◽  
O. I. Sushkov ◽  
A. A. Ponomarenko ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Peritoneal Carcinomatosis ◽  
Cancer Patients ◽  
Somatic Mutations ◽  
Disease Free Survival ◽  
Free Survival ◽  
The Status ◽  
Colorectal Cancer Patients ◽  
Disease Free

Purpose: to evaluate the effect of somatic mutations of the KRAS, NRAS, BRAF genes and the status of microsatellite instability on the overall and disease-free survival of patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.Material and Methods. From 2012 to 2018, the study included 45 patients who underwent surgery for synchronous peritoneal carcinomatosis with colorectal cancer. In all patients, mutations of the KRAS, NRAS, BRAF genes and MSI status of the tumor and peritoneum metastases were determined using Sanger sequencing, fragment analysis and digital droplet polymerase chain reaction. The effect of mutations on patient survival was evaluated.Results. The prevalence of somatic mutations was 69 % of patients. The discordance between the tumor and peritoneum metastases was 9 %. All tumors and peritoneum metastases were microsatellite stable. KRAS, NRAS, BRAF mutations did not affect the overall and disease-free survival (p=0.87 and p=0.85, respectively).Conclusion. Somatic mutations in the KRAS, NRAS, or BRAF genes are not a prognostic factor affecting the overall and relapse-free survival of colorectal cancer patients with peritoneal carcinomatosis. The molecular status of primary tumor may differ from the status of peritoneal metastasis. It should be taken into account when prescribing targeted drugs. 

scholarly journals STIL Endows Oncogenic and Stem-Like Attributes to Colorectal Cancer Plausibly by Shh and Wnt Signaling

2021 ◽  
Vol 11 ◽  
Author(s):  
Tapas Pradhan ◽  
Vikas Kumar ◽  
Evangeline Surya H ◽  
R. Krishna ◽  
Samu John ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Importance ◽  
Disease Free Survival ◽  
Drug Resistant ◽  
Free Survival ◽  
Shh Pathway ◽  
Disease Free

The discovery of a potent gene regulating tumorigenesis and drug resistance is of high clinical importance. STIL is an oncogene; however, its molecular associations and role in colorectal oncogenesis are unknown. In this study, we have explored the role of STIL gene in tumorigenesis and studied its molecular targets in colorectal cancer (CRC). STIL silencing reduced proliferation and tumor growth in CRC. Further, STIL was found to regulate stemness markers CD133 and CD44 and drug resistant markers thymidylate synthase, ABCB1, and ABCG2 both in in-vitro and in-vivo CRC models. In addition, high expression of STIL mRNA was found to be associated with reduced disease-free survival in CRC cases. Interestingly, we observed that STIL-mediated regulation of stemness and drug resistant genes is not exclusively governed by Sonic hedgehog (Shh) signaling. Remarkably, we found STIL regulate β-catenin levels through p-AKT, independent of Shh pathway. This partially answers Shh independent regulatory mechanism of cancer stem cell (CSC) markers by STIL. Our study suggests an instrumental role of STIL in molecular manifestation of CRC and progression.

scholarly journals A Novel Digital Score for Abundance of Tumour Infiltrating Lymphocytes Predicts Disease Free Survival in Oral Squamous Cell Carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Muhammad Shaban ◽  
Syed Ali Khurram ◽  
Muhammad Moazam Fraz ◽  
Najah Alsubaie ◽  
Iqra Masood ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Free Survival ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Abstract Oral squamous cell carcinoma (OSCC) is the most common type of head and neck (H&N) cancers with an increasing worldwide incidence and a worsening prognosis. The abundance of tumour infiltrating lymphocytes (TILs) has been shown to be a key prognostic indicator in a range of cancers with emerging evidence of its role in OSCC progression and treatment response. However, the current methods of TIL analysis are subjective and open to variability in interpretation. An automated method for quantification of TIL abundance has the potential to facilitate better stratification and prognostication of oral cancer patients. We propose a novel method for objective quantification of TIL abundance in OSCC histology images. The proposed TIL abundance (TILAb) score is calculated by first segmenting the whole slide images (WSIs) into underlying tissue types (tumour, lymphocytes, etc.) and then quantifying the co-localization of lymphocytes and tumour areas in a novel fashion. We investigate the prognostic significance of TILAb score on digitized WSIs of Hematoxylin and Eosin (H&E) stained slides of OSCC patients. Our deep learning based tissue segmentation achieves high accuracy of 96.31%, which paves the way for reliable downstream analysis. We show that the TILAb score is a strong prognostic indicator (p = 0.0006) of disease free survival (DFS) on our OSCC test cohort. The automated TILAb score has a significantly higher prognostic value than the manual TIL score (p = 0.0024). In summary, the proposed TILAb score is a digital biomarker which is based on more accurate classification of tumour and lymphocytic regions, is motivated by the biological definition of TILs as tumour infiltrating lymphocytes, with the added advantages of objective and reproducible quantification.

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