Association between Altered Oncogenic Signaling Pathways and Overall Survival of Patients with Metastatic Colorectal Cancer

Huang, Yi-Hsuan; Lin, Peng-Chan; Su, Wu‐Chou; Chan, Ren‐Hao; Chen, Po-Chuan; Lin, Bo; Shen, Meng-Ru; Chen, Shang-Hung; Yeh, Yu-Min

doi:10.3390/diagnostics11122308

Cited by 6 publications

(3 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The TGF-β signaling pathway regulates tissue development and homeostasis, and genomic alterations in this signaling pathway are involved in CRC progression ( 36 , 37 ). Genomic TGF-β pathway alterations have been identified in 30% of rectosigmoid junction or rectum cancer patients and only 12% of in sigmoid colon cancer patients ( 38 ). Research using The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center data sets have shown that alterations in the TGF-β pathway are correlated with worse overall survival in patients with metastatic CRC ( 39 , 40 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehension of rectosigmoid junction cancer molecular features by comparison to the rectum or sigmoid colon cancer

Zhu¹,

Zhu²,

Zhang³

et al. 2023

J Gastrointest Oncol

View full text Add to dashboard Cite

Background Colorectal cancer (CRC) is a heterogeneous cancer. Its treatment depends on its anatomical site and molecular features. Carcinomas of the rectosigmoid junction are frequent; however, specific data on these tumors are sparse, as they are frequently assigned to either the colon or rectum. This study sought to identify the molecular features of rectosigmoid junction cancer to determine whether there should be any difference between the therapeutic management of rectosigmoid junction cancer and that of sigmoid colon or rectum cancer. Methods The data of 96 CRC patients with carcinomas in the sigmoid colon, rectosigmoid junction, and rectum were retrospectively summarized. The next-generation sequencing (NGS) data of the patients were analyzed to study the molecular characteristics of the carcinomas in different locations of the bowel. Results In total, there was no difference in the clinicopathologic characteristics of the three groups. TP53 , APC , and KRAS genes were the top 3 alteration genes in sigmoid colon, rectosigmoid junction, and rectum cancer. The rates of the KRAS , NRAS , and PIK3CA increased as the location moved distally, while the rates of APC and BRAF decreased. Almost no significant molecular differences were found among the three groups. The prevalence of the FLT3 , fms-related tyrosine kinase 1 ( FLT1 ), and phosphoenolpyruvate carboxykinase 1 ( PCK1 ) mutation was lower in the rectosigmoid junction group than the sigmoid colon and rectum groups (P>0.05). The proportion of the transforming growth factor beta pathway was higher in the rectosigmoid junction and rectum groups than the sigmoid colon group (39.3% vs. 34.3% vs. 18.2%, respectively, P=0.121, P=0.067, P=0.682); a higher proportion of MYC pathway was also observed in the rectosigmoid junction than that in rectum and sigmoid colon (28.6% vs. 15.2% vs. 17.1%, P=0.278, P=0.202, P=0.171). Regardless of the clustering method employed, the patients were divided into two clusters, and the composition of clusters revealed no significant differences in terms of the different locations. Conclusions Rectosigmoid junction cancer has a distinctive molecular profile compared to the molecular profiles of the adjacent bowel segment cancers.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehension of rectosigmoid junction cancer molecular features by comparison to the rectum or sigmoid colon cancer

Zhu¹,

Zhu²,

Zhang³

et al. 2023

J Gastrointest Oncol

View full text Add to dashboard Cite

show abstract

“…A previous study reported that the RTK-RAS pathway is related to the pathogenesis of CRC ( 22 ) and mutations in the RTK-RAS pathway led to decreased relapse free survival (RFS) in CRC patients ( 23 ). The Cancer Genome Atlas Pan-Cancer Analysis Project examined 123 patients with non-MSI, highly metastatic CRC, and found significant changes in the RTK-RAS, Notch, Wnt, p53, PI3K, TGF-β, and Myc pathways ( 24 ). These changes in the RTK-RAS and Notch pathway have been shown to be strongly related to poor OS in patients whose colorectal liver metastases were resected ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

DNAH7 mutations benefit colorectal cancer patients receiving immune checkpoint inhibitors

Yang¹,

Shen²,

Yang³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

Background: Colorectal cancer (CRC) is a malignant tumor associated with a high mortality rate. While the advent of immune checkpoint inhibitors (ICIs) has been a gamechanger, only a small percentage of CRC patients benefit from ICIs. The pathological mechanism of CRC is not well understood, but somatic mutations, especially missense mutations, are believed to play an important role. This study examined the relationship between ICIs in colorectal cancer and missense mutations in the axonemal dynein heavy chain gene 7 (DNAH7).Methods: A clinical cohort (n=690) and the CRC data from the publicly available Cancer Genome Atlas (TCGA) were examined. Gene Set Enrichment Analysis, ESTIMATE analysis, and clinical correlation analysis were performed to explore the effects and mechanisms of DNAH7 mutation on immunotherapy in colorectal cancer. Results:The results showed that CRC patients with DNAH7 mutations can benefit more from ICIs (P<0.05). Patients with DNAH7 mutation had higher ESTIMATE scores, immune scores, and matrix scores, compared to patients without the DNAH7 mutation (P<0.001). The transport of small molecules, keratinization, asthma, autoimmune thyroid disease, allograft rejection, and other pathways were significantly enriched in DNAH7 mutated tissues (P<0.05). The top key genes associated with the DNAH7 mutation included AQP8, MS4A12, GUCA2B, and ZG16 (P<0.01). Conclusions:The current study not only demonstrated the significance of DNAH7 as a risk factor and prognostic feature in CRC, but also revealed that DNAH7 mutations might affect the clinical efficacy of ICIs by impacting the tumor immune microenvironment.

show abstract

“…In CRC, SMAD4 is one of the most frequently mutated genes based on a series of high-throughput analyses. A recent study utilizing next-generation sequencing (NGS) including 123 non-MSI-high mCRC patients demonstrated an about 20% mutation occurrence of SMAD4 [37]. TGFBR2 mutations are also often shown in CRC [38].…”

Section: Role Of Tgf-β Signaling In the Carcinogenesis And Progressio...mentioning

confidence: 99%

The Role of the Transforming Growth Factor-β Signaling Pathway in Gastrointestinal Cancers

Matsuoka,

Yashiro

2023

Biomolecules

View full text Add to dashboard Cite

Transforming growth factor-β (TGF-β) has attracted attention as a tumor suppressor because of its potent growth-suppressive effect on epithelial cells. Dysregulation of the TGF-β signaling pathway is considered to be one of the key factors in carcinogenesis, and genetic alterations affecting TGF-β signaling are extraordinarily common in cancers of the gastrointestinal system, such as hereditary nonpolyposis colon cancer and pancreatic cancer. Accumulating evidence suggests that TGF-β is produced from various types of cells in the tumor microenvironment and mediates extracellular matrix deposition, tumor angiogenesis, the formation of CAFs, and suppression of the anti-tumor immune reaction. It is also being considered as a factor that promotes the malignant transformation of cancer, particularly the invasion and metastasis of cancer cells, including epithelial-mesenchymal transition. Therefore, elucidating the role of TGF-β signaling in carcinogenesis, cancer invasion, and metastasis will provide novel basic insight for diagnosis and prognosis and the development of new molecularly targeted therapies for gastrointestinal cancers. In this review, we outline an overview of the complex mechanisms and functions of TGF-β signaling. Furthermore, we discuss the therapeutic potentials of targeting the TGF-β signaling pathway for gastrointestinal cancer treatment and discuss the remaining challenges and future perspectives on targeting this pathway.

show abstract

Association between Altered Oncogenic Signaling Pathways and Overall Survival of Patients with Metastatic Colorectal Cancer

Cited by 6 publications

References 54 publications

Comprehension of rectosigmoid junction cancer molecular features by comparison to the rectum or sigmoid colon cancer

Comprehension of rectosigmoid junction cancer molecular features by comparison to the rectum or sigmoid colon cancer

DNAH7 mutations benefit colorectal cancer patients receiving immune checkpoint inhibitors

The Role of the Transforming Growth Factor-β Signaling Pathway in Gastrointestinal Cancers

Contact Info

Product

Resources

About