Effect of KRAS and NRAS mutations on the prognosis of patients with synchronous metastatic colorectal cancer presenting with liver‑only and lung‑only metastases

Chuang, Shih‐Chang; Huang, Ching‐Wen; Chen, Yi‐Ting; Ma, Cheng‐Jen; Tsai, Hsiang‐Lin; Chang, Tsung‐Kun; Su, Wei‐Chih; Hsu, Wen‐Hung; Kuo, Chao‐Hung; Wang, Jaw‐Yuan

doi:10.3892/ol.2020.11795

Cited by 16 publications

(11 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the mutation in KRAS is an early and dominant event, amplification and overexpression of KRAS, leading to activation of the KRAS/MAPK pathway, can also be observed in colorectal cancer patients [35]. Considering that KRAS mutations have been thoroughly investigated in CRC [36][37][38], we focused our study on patients negative for the most common KRAS activating mutations and showed that wild-type KRAS protein expression could be regulated via miR-544a-3p expression and let-7a-5p KRAS-LCS6 T/G polymorphism.…”

Section: Discussionmentioning

confidence: 99%

Regulation of KRAS protein expression by miR-544a and KRAS-LCS6 polymorphism in wild-type KRAS sporadic colon adenocarcinoma

et al. 2021

View full text Add to dashboard Cite

Colorectal carcinoma (CRC) results from the accumulation of genetic mutations and alterations in signaling pathways. KRAS is mutated in 40% of CRC cases and is involved in increased tumor cells proliferation and survival. Although KRAS mutations are a dominant event in CRC tumorigenesis, increased wild-type KRAS expression has a similar effect on accelerated tumor growth. In this study, we investigated the KRAS status in correlation with clinicopathological features in sporadic CRC and more importantly the role of let-7a-5p and miR-544a-3p in the regulation of wild-type KRAS protein expression in the tumor center (T1) and invasive tumor front (T2).Analysis showed that 39.1% of tumor samples had KRAS mutations. In wild-type KRAS tumors, 62.0% were positive for KRAS protein expression and there was a higher percentage of KRAS positive tumor cells and a higher intensity of immunohistochemical reaction in T2 than in T1 samples. This could not be attributed to differences in KRAS mRNA levels, suggesting regulation via miR-544a-3p expression which was significantly decreased in T2 samples. Furthermore, we demonstrated that tumor samples carrying the KRAS-LCS6 variant allele had significantly higher protein expression of the wild-type KRAS.Our results suggest the role of the KRAS-LCS6 polymorphism and miR-544a-3p expression in the regulation of wild-type KRAS protein expression in sporadic CRC.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of KRAS protein expression by miR-544a and KRAS-LCS6 polymorphism in wild-type KRAS sporadic colon adenocarcinoma

et al. 2021

View full text Add to dashboard Cite

show abstract

“…All the primers were produced with standard molecular biology quality (Protech Technology Enterprise Co., Ltd., Taipei, Taiwan). RAS mutations were identified through direct DNA sequencing, the procedure for which was described in detail in our previous study [17]. Both KRAS and NRAS mutation statuses were examined in the patients.…”

Section: Analysis Of Braf Mutation Ras Mutation and Status Of Microsa...mentioning

confidence: 99%

BRAF, MEK, and EGFR Triplet Inhibitors as Salvage Therapy in BRAF-Mutated Metastatic Colorectal Cancer—A Case Series Study Target Therapy of BRAF-Mutated mCRC

et al. 2021

View full text Add to dashboard Cite

Background and objectives: Patients with BRAF-mutated metastatic colorectal cancer have considerably poorer responses to conventional systemic treatment. The real-world effects of triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in Asia have not been well-reported. Materials and Methods: This single-center case series included patients with BRAF-mutated metastatic colorectal cancer undergoing triplet therapy after failure of prior systemic treatment from 2016 to 2020. The primary outcome was progression-free survival, and secondary outcomes were overall survival, response rate, disease control rate, and adverse events. Results: Nine eligible patients with BRAF-mutated metastatic colorectal cancer receiving triplet therapy were enrolled, with a median follow-up time of 14.5 months (range, 1–26). Most patients (88.8%) had two or more prior systemic treatments, and the triplet regimen was mainly dabrafenib, trametinib, and panitumumab. The overall response rate and disease control rate were 11.1% and 33.3%, respectively. Median progression-free survival and overall survival were 2.9 and 7.4 months, respectively, and a trend toward better overall survival was found with left-sided metastatic colorectal cancer compared with right-sided disease (9.2 vs. 6.9 months, p = 0.093). Adverse events were mostly Grade 1–2, including nausea, hypertension, gastrointestinal symptoms, and skin disorders. Conclusions: In this single-center case series, triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in BRAF-mutated metastatic colorectal cancer had an acceptable safety profile and reasonable efficacy.

show abstract

“…In another study, the effect of K-Ras and N-Ras mutation on the prognosis of mCRC specifically in the case of liver-metastasis (LiM) and lung- metastasis (LuM) was assessed. K-Ras as well as N-Ras mutation affected the PFS and the OS of mCRC patients in the case of (LiM) but not in (LuM) [ 187 ]. In a subset of CRC patients who underwent hepatic resection, K-Ras mutations were negatively associated with OS and relapse-free survival (RFS) as well [ 188 ].…”

Section: Future Recommendations For Devising Isoform-specific Targetingmentioning

confidence: 99%

Ras Isoforms from Lab Benches to Lives—What Are We Missing and How Far Are We?

Nair

Kubatzky

Saha

2021

IJMS

View full text Add to dashboard Cite

The central protein in the oncogenic circuitry is the Ras GTPase that has been under intense scrutiny for the last four decades. From its discovery as a viral oncogene and its non–oncogenic contribution to crucial cellular functioning, an elaborate genetic, structural, and functional map of Ras is being created for its therapeutic targeting. Despite decades of research, there still exist lacunae in our understanding of Ras. The complexity of the Ras functioning is further exemplified by the fact that the three canonical Ras genes encode for four protein isoforms (H-Ras, K-Ras4A, K-Ras4B, and N-Ras). Contrary to the initial assessment that the H-, K-, and N-Ras isoforms are functionally similar, emerging data are uncovering crucial differences between them. These Ras isoforms exhibit not only cell–type and context-dependent functions but also activator and effector specificities on activation by the same receptor. Preferential localization of H-, K-, and N-Ras in different microdomains of the plasma membrane and cellular organelles like Golgi, endoplasmic reticulum, mitochondria, and endosome adds a new dimension to isoform-specific signaling and diverse functions. Herein, we review isoform-specific properties of Ras GTPase and highlight the importance of considering these towards generating effective isoform-specific therapies in the future.

show abstract

Effect of KRAS and NRAS mutations on the prognosis of patients with synchronous metastatic colorectal cancer presenting with liver‑only and lung‑only metastases

Cited by 16 publications

References 44 publications

Regulation of KRAS protein expression by miR-544a and KRAS-LCS6 polymorphism in wild-type KRAS sporadic colon adenocarcinoma

Regulation of KRAS protein expression by miR-544a and KRAS-LCS6 polymorphism in wild-type KRAS sporadic colon adenocarcinoma

BRAF, MEK, and EGFR Triplet Inhibitors as Salvage Therapy in BRAF-Mutated Metastatic Colorectal Cancer—A Case Series Study Target Therapy of BRAF-Mutated mCRC

Ras Isoforms from Lab Benches to Lives—What Are We Missing and How Far Are We?

Contact Info

Product

Resources

About