Metastatic colorectal cancer and type 2 diabetes: prognostic and genetic interactions

Ottaiano, Alessandro; Circelli, Luisa; Santorsola, Mariachiara; Savarese, Giovanni; Fontanella, Daniela; Gigantino, Valerio; Mauro, Annabella Di; Capuozzo, Maurizio; Zappavigna, Silvia; Lombardi, Angela; Perri, Francesco; Cascella, Marco; Granata, Vincenza; Nasti, Guglielmo; Caraglia, Michele

doi:10.1002/1878-0261.13122

Cited by 17 publications

(11 citation statements)

References 67 publications

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“…These patients can present with high-risk pathological features, including T3 and T4 tumors, which were also observed. A recent study also pointed out this association between T2DM and metastases to lymph nodes (p < 0.01) [20].…”

Section: Discussionmentioning

confidence: 78%

Prognostic Impact of Type 2 Diabetes in Metastatic Colorectal Cancer

Baleiras¹,

Domingues²,

Severino³

et al. 2023

Cureus

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BackgroundDiabetes mellitus (DM) is a prognostic factor for some malignancies, but its clinical implications in metastatic colorectal cancer (mCRC) patients are less clear. Therefore, we conducted a retrospective study to evaluate the impact of pre-existing type 2 diabetes mellitus (T2DM) on the survival outcomes of patients with newly diagnosed mCRC. MethodologyWe retrospectively included patients with newly diagnosed mCRC between January 2017 and June 2021 and with pre-existing T2DM. Data on the characteristics of patients, clinicopathological features, and drug exposure were collected from the electronic medical records. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and treatment-related adverse events (TRAEs). ResultsAmong 187 mCRC patients, 54 (28.8%) had T2DM. The median follow-up was 25 months. We observed 150 OS events and 168 PFS events. Diabetes significantly and negatively impacted PFS and OS. The median for PFS (mPFS) was eight and 16 months for T2DM and no T2DM patients, respectively (p < 0.0001; log-rank test). The median overall survival (mOS) was 15 and 29 months for T2DM and no T2DM patients, respectively (p < 0.0001; log-rank test). Patients with diabetes were more often overweight or obese (59.3% vs. 24.8%; p < 0.01) and had a poorer performance status (53.7% vs. 21.1% with Eastern Cooperative Oncology Group Performance Status 1; p < 0.01). Additionally, T2DM patients had more high-risk pathological features, including G3 grading tumors (27.7% vs. 12.0%; p = 0.01), lymph node involvement (p < 0.01), BRAF-mutated (35.1% vs. 6.8%; p < 0.01), and right-sided CRC (63.0% vs. 30.1%; p < 0.01). We found no statistically significant differences in TRAEs. Nevertheless, a significantly higher rate of grade 2-4 peripheral neuropathy (22.2% vs. 5.3%; p < 0.01) was reported in T2DM patients. ConclusionsT2DM is a negative prognostic factor for survival in mCRC. The paper provides empirical evidence in favor of the joint control of both pathologies. Further research is needed to establish the robustness of our results.

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Section: Discussionmentioning

confidence: 78%

Prognostic Impact of Type 2 Diabetes in Metastatic Colorectal Cancer

Baleiras¹,

Domingues²,

Severino³

et al. 2023

Cureus

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“…Moreover, we previously reported that certain genes associated with type 2 diabetes (T2D) may also play a role in the malignant phenotype of OMD in CRC [ 104 ]. In particular, some variants associated with T2D, such as HNF1A p.I27L, IDE3 p.T105A, IRS1 p.S892G, and INSR p.A2G, although considered benign, could influence the activity of related proteins.…”

Section: Biomarkers Of Omdmentioning

confidence: 99%

Oligo-Metastatic Cancers: Putative Biomarkers, Emerging Challenges and New Perspectives

Ottaiano

Santorsola

Circelli³

et al. 2023

Cancers

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Some cancer patients display a less aggressive form of metastatic disease, characterized by a low tumor burden and involving a smaller number of sites, which is referred to as “oligometastatic disease” (OMD). This review discusses new biomarkers, as well as methodological challenges and perspectives characterizing OMD. Recent studies have revealed that specific microRNA profiles, chromosome patterns, driver gene mutations (ERBB2, PBRM1, SETD2, KRAS, PIK3CA, SMAD4), polymorphisms (TCF7L2), and levels of immune cell infiltration into metastases, depending on the tumor type, are associated with an oligometastatic behavior. This suggests that OMD could be a distinct disease with specific biological and molecular characteristics. Therefore, the heterogeneity of initial tumor burden and inclusion of OMD patients in clinical trials pose a crucial methodological question that requires responses in the near future. Additionally, a solid understanding of the molecular and biological features of OMD will be necessary to support and complete the clinical staging systems, enabling a better distinction of metastatic behavior and tailored treatments.

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“…Existing evidences show disorders of glucose and lipids metabolism, such as diabetes and obesity, are critical promoters of tumor metastasis (8)(9)(10). Diabetes patients are always accompanied by excessive reactive oxygen species formation, chronic inflammation, and healing barrier, which contribute to its carcinogenicity (11)(12)(13). Interestingly, some anti-diabetic drugs possess anti-tumor effects, which implies hyperglycemia can accelerate tumor progression (14,15).…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a nomogram to predict occult cervical metastasis in early oral squamous cell carcinoma

Xu¹,

Chen²,

Yin³

et al. 2023

Ann Transl Med

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Background: Lack of adequate objectivity and universality, available models are still difficult to be applied to clinical practice in predicting occult cervical metastasis of early oral squamous cell carcinoma (OSCC).Taking abnormal metabolic state into consideration, the current model is helpful to distinguish those patients with or without occult cervical metastasis.Methods: This study retrospectively analyzed 330 OSCC patients initially diagnosed cT1-2N0M0 stage and received neck dissection from January 2020 to July 2022. The occult cervical metastasis was identified by pathological examination.. After screening independent risk factors using logistic regression, patients were divided into training and validation cohorts at the ratio of 2:1 randomly, and a novel diagnostic model was constructed. Performances of this model were evaluated by the area under the curve (AUC), calibrating curve, decision curve analysis (DCA) and clinical impact curve (CIC).Results: Of the 330 included patients {age mean [standard deviation (SD)], 61.24 (12.99) years; 202 (61.2%) males}, 49 (14.8%) had occult nodal metastasis. Five variables, including body mass index (BMI) [high odds

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Metastatic colorectal cancer and type 2 diabetes: prognostic and genetic interactions

Cited by 17 publications

References 67 publications

Prognostic Impact of Type 2 Diabetes in Metastatic Colorectal Cancer

Prognostic Impact of Type 2 Diabetes in Metastatic Colorectal Cancer

Oligo-Metastatic Cancers: Putative Biomarkers, Emerging Challenges and New Perspectives

Development and validation of a nomogram to predict occult cervical metastasis in early oral squamous cell carcinoma

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