Prognostic factors of survival in stage IV colorectal cancer with synchronous liver metastasis: Negative effect of the KRAS mutation

Díez-Alonso, Manuel; Mendoza‐Moreno, Fernando; Jiménez‐Alvárez, Laura; Núñez, Óscar; Blázquez‐Martín, Alma; Sánchez-Gollarte, Ana; Matías‐García, Belén; Molina, Raquel; San-Juan, Alberto; Gutiérrez‐Calvo, Alberto

doi:10.3892/mco.2021.2255

Cited by 4 publications

(2 citation statements)

References 25 publications

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“…Stage IV indicates that cancer has spread to other tissues and organs and that outcomes for these patients are very poor [ 28 ]. There are few established prognostic factors for stage IV COAD, including the mutation status of BRAF and KRAS [ 29 , 30 , 31 ], and histological subtype [ 32 ]. Stratification factors for future studies evaluating new cancer treatments, including immunotherapy, are required.…”

Section: Discussionmentioning

confidence: 99%

Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance

Ustjanzew

Sencio

Trottein

et al. 2022

IJMS

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Non-conventional T cells, such as γδ T and invariant natural killer T (iNKT) cells, are emerging players in fighting cancer. Alpha-galactosylceramide (α-GalCer) is used as an exogenous ligand to activate iNKT cells. Human cells don’t have a direct pathway producing α-GalCer, which, however, can be produced by bacteria. We searched the literature for bacteria strains that are able to produce α-GalCer and used available sequencing data to analyze their presence in human tumor tissues and their association with survival. The modulatory effect of antibiotics on the concentration of α-GalCer was analyzed in mice. The human gut bacteria Bacteroides fragilis, Bacteroides vulgatus, and Prevotella copri produce α-GalCer structures that are able to activate iNKT cells. In mice, α-GalCer was depleted upon treatment with vancomycin. The three species were detected in colon adenocarcinoma (COAD) and rectum adenocarcinoma tissues, and Prevotella copri was also detected in bone tumors and glioblastoma tissues. Bacteroides vulgatus in COAD tissues correlated with better survival. In conclusion, α-GalCer-producing bacteria are part of the human gut microbiome and can infiltrate tumor tissues. These results suggest a new mechanism of interaction between bacteria and immune cells: α-GalCer produced by bacteria may activate non-conventional T cells in tumor tissues, where they can exert a direct or indirect anti-tumor activity.

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Section: Discussionmentioning

confidence: 99%

Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance

Ustjanzew

Sencio

Trottein

et al. 2022

IJMS

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“…A study of epidermal growth factor receptor (EGFR) inhibitors combined with third-line chemotherapy in metastatic CRC patients found that the RAS mutation was an independent predictor for shorter PFS [ 30 ]. A retrospective study based on locally advanced rectal cancer patients treated with neoadjuvant chemoradiation therapy (nCRT) and proctectomy showed that KRAS mutations were not associated with a pathologic complete response (pCR), yet they were independently related to a worse prognosis [ 31 ]. Another study of stage IV CRC patients found a shorter OS for patients with KRAS mutations versus wild-type status ( p = 0.004) [ 32 ].…”

Section: Kras Mutations In Cancersmentioning

confidence: 99%

KRAS Mutations in Solid Tumors: Characteristics, Current Therapeutic Strategy, and Potential Treatment Exploration

Yang

Zhang

Huang

et al. 2023

JCM

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Kristen rat sarcoma (KRAS) gene is one of the most common mutated oncogenes in solid tumors. Yet, KRAS inhibitors did not follow suit with the development of targeted therapy, for the structure of KRAS has been considered as being implausible to target for decades. Chemotherapy was the initial recommended therapy for KRAS-mutant cancer patients, which was then replaced by or combined with immunotherapy. KRAS G12C inhibitors became the most recent breakthrough in targeted therapy, with Sotorasib being approved by the Food and Drug Administration (FDA) based on its significant efficacy in multiple clinical studies. However, the subtypes of the KRAS mutations are complex, and the development of inhibitors targeting non-G12C subtypes is still at a relatively early stage. In addition, the monotherapy of KRAS inhibitors has accumulated possible resistance, acquiring the exploration of combination therapies or next-generation KRAS inhibitors. Thus, other non-target, conventional therapies have also been considered as being promising. Here in this review, we went through the characteristics of KRAS mutations in cancer patients, and the prognostic effect that it poses on different therapies and advanced therapeutic strategy, as well as cutting-edge research on the mechanisms of drug resistance, tumor development, and the immune microenvironment.

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Long-term prognosis of patients with pT1-2 colorectal cancer unaffected by lymph node metastasis

Song,

Wang,

Chen

et al. 2024

Preprint

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Background/Aim: Our goal was to investigate patients with pT1-2 colorectal cancer (CRC) in terms of lymph node metastasis (LNM) and its clinical implications, perhaps questioning the staging of such tumors. Patients and Methods: This retrospective cohort study took place at a high-volume cancer center in Japan. We stratified patients with pT1-2 CRC (n=1288) by presence (LNM+) or absence (LNM-) of LNM, assessing overall (OS), cancer-specific (CSS), and relapse-free (RFS) survival rates in both groups before and after propensity score matching (PSM). COX multivariate analysis served for screening of prognostic risk factors. Results: Lymph node metastasis was ultimately confirmed in 256 study subjects (19.9%). Before matching, tumors of the LNM+ (vs LNM-) group were more inclined to be fairly large (≥2 cm: 76.6% vs 61.2%; p<0.001), with greater propensity for infiltrating or ulcerative features (55.1% vs 36.2%; p<0.001) and histotypes of lesser differentiation (Mod/Poor/Sig/Muc: 65.6% vs 45.8%; p<0.001). Likewise, they showed greater tendency for aggressive growth (91.1% vs 81.1%; p<001), lymphatic (44.5% vs 19.4%; p<0.001) or vascular (59% vs 35.1%; p<0.001) invasion, and prolific lymph node harvesting (23.6±12.2 vs 21.7±12.3; p=0.025). Although similar in terms of OS (LNM-, 94.2%; LNM+, 91.8%; p=0.339), the LNM- (vs LNM+) group displayed significantly better CSS (99.5% vs 96.9%; p<0.001) and RFS (97.2% vs 89.5%; p<0.001). After matching, RFS still proved significantly better in the LNM- (vs LNM+) group (95.9% vs 89.8%; p=0.016), with multivariate analysis identifying LNM+ as an independent risk factor for RFS before and after PSM. A higher recurrence rate was also evident in the LNM+ (vs LNM-) group (before matching: 10.5% vs 2.8%, [p<0.001]; after matching: 10.2% vs 4.1% [p=0.008]), involving liver and lymph nodes primarily. Neither OS nor CSS differed significantly by group. Conclusion: In patients with pT1-2N+ CRC, we found greater risk of hepatic or nodal recurrence, compared with node-negative counterparts. However, long-term survival was unaffected. Appropriate downstaging of pT1-2N+ CRC from stage IIIA is therefore a reasonable prospect.

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Prognostic factors of survival in stage IV colorectal cancer with synchronous liver metastasis: Negative effect of the KRAS mutation

Cited by 4 publications

References 25 publications

Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance

Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance

KRAS Mutations in Solid Tumors: Characteristics, Current Therapeutic Strategy, and Potential Treatment Exploration

Long-term prognosis of patients with pT1-2 colorectal cancer unaffected by lymph node metastasis

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