Molecular Profile of Colorectal Cancer Patients in Bali Based on Methylation of O6-Methylguanine DNA Methyltransferase Promoter Region and Mutation of BRAF and Kirsten RAt Sarcoma Viral Oncogene Homolog Gene

e15524 Background: Efforts by previous study had provided molecular profile of MSS & TMB-H gastrointestinal (GI) cancers, however, Asian patients were underrepresented in this study. We aim to investigate specific molecular features of Chinese MSS & TMB-H colorectal cancer patients. Methods: FFPE tumor samples from 249 Chinese colorectal cancer patients with MSS & TMB-H (Chinese cohort) were sequencing using a panel targeting 539 cancer-related genes of the human genome. Genomic data from our cohort was compared with publicly available data from 508 MSS & TMB-H colorectal cancer patients from the TCGA dataset (TCGA cohort). TMB was calculated on the two cohorts following the same criteria. TMB-H was defined as the top quartile of all TMB values. Results: In total, 48 (19%) MSS & TMB-H patients were found in Chinese cohort, and 55 (10%) were found in TCGA cohort. Based on the analysis of the genetic alteration profile from our cohort, in MSS & TMB-H colorectal cancer patients, APC (85%), TP53 (81%), KRAS (44%), and LRP1B (378%) as the most commonly altered genes. In TCGA cohort, TTN (84%), APC (80%), TP53 (64%), SYNE1 (51%), and MUC16 (51%) as the most commonly altered genes. On the other hand, the most difference genes between MSS & TMB-H group and MSS/TMB-L group in TCGA cohort were TNN (84% vs. 52%; p = 0.000008), SYNE1 (56% vs. 24%; p = 0.000003), MUC16 (51% vs. 23%; p = 0.00006), FAT4 (47% vs. 16%; p = 0.000002), RYR2 (44%vs. 16%; p = 0.00001). Compared with TCGA cohort, LRP1B (38% vs. 13%; p = 0.0005), TCF7L2 (33% vs. 8%; p = 0.00003), SPTA1 (29% vs. 6%; p = 0.00005), PREX2 (19% vs. 3%; p = 0.0006) were the most difference genes between MSS & TMB-H group and MSS/TMB-L group in Chinese cohort. Conclusions: Our study contributes to the understanding of specific genetic alterations harbored by MSS & TMB-H colorectal cancer patients that could potentially be developed as markers of precision medicine.

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Molecular profile in Paraguayan colorectal cancer patients, towards to a precision medicine strategy

Cancer Medicine ◽

10.1002/cam4.2191 ◽

2019 ◽

Vol 8 (6) ◽

pp. 3120-3130

Author(s):

Tania Fleitas-Kanonnikoff ◽

Carolina Martinez‐Ciarpaglini ◽

Josefina Ayala ◽

Cinthia Gauna ◽

Rita Denis ◽

...

Keyword(s):

Colorectal Cancer ◽

Precision Medicine ◽

Cancer Patients ◽

Molecular Profile ◽

Colorectal Cancer Patients

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A Snapshot of The Tumor Microenvironment in Colorectal Cancer: The Liquid Biopsy

International Journal of Molecular Sciences ◽

10.3390/ijms20236016 ◽

2019 ◽

Vol 20 (23) ◽

pp. 6016 ◽

Cited By ~ 6

Author(s):

Mercedes Herrera ◽

Cristina Galindo-Pumariño ◽

Vanesa García-Barberán ◽

Cristina Peña

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

Cancer Patients ◽

Cancer Progression ◽

Stromal Cells ◽

Liquid Biopsy ◽

Therapeutic Potential ◽

Molecular Profile ◽

Invasive Approach ◽

Colorectal Cancer Patients

The molecular profile of liquid biopsies is emerging as an alternative to tissue biopsies in the clinical management of malignant diseases. In colorectal cancer, significant liquid biopsy-based biomarkers have demonstrated an ability to discriminate between asymptomatic cancer patients and healthy controls. Furthermore, this non-invasive approach appears to provide relevant information regarding the stratification of tumors with different prognoses and the monitoring of treatment responses. This review focuses on the tumor microenvironment components which are detected in blood samples of colorectal cancer patients and might represent potential biomarkers. Exosomes released by tumor and stromal cells play a major role in the modulation of cancer progression in the primary tumor microenvironment and in the formation of an inflammatory pre-metastatic niche. Stromal cells-derived exosomes are involved in driving mechanisms that promote tumor growth, migration, metastasis, and drug resistance, therefore representing substantial signaling mediators in the tumor-stroma interaction. Besides, recent findings of specifically packaged exosome cargo in Cancer-Associated Fibroblasts of colorectal cancer patients identify novel exosomal biomarkers with potential clinical applicability. Furthermore, additional different signals emitted from the tumor microenvironment and also detectable in the blood, such as soluble factors and non-tumoral circulating cells, arise as novel promising biomarkers for cancer diagnosis, prognosis, and treatment response prediction. The therapeutic potential of these factors is still limited, and studies are in their infancy. However, innovative strategies aiming at the inhibition of tumor progression by systemic exosome depletion, exosome-mediated circulating tumor cell capturing, and exosome-drug delivery systems are currently being studied and may provide considerable advantages in the near future.

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