Insulin‐like growth factor 2: a poor prognostic biomarker linked to racial disparity in women with uterine carcinosarcoma

Arsdale, A.R. Van; Arend, Rebecca C.; Cossio, M.; Erickson, Britt; Wang, Yanhua; Doo, David W.; Leath, Charles A.; Goldberg, Gary L.; Huang, Gloria S.

doi:10.1002/cam4.1335

Cited by 6 publications

(5 citation statements)

References 40 publications

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“…This evidence also indicates that activation of the IGF-II locus may promote EMT [191] that could then facilitate tumor invasion and metastasis. This is consistent with reports that IGF-II is associated with progression and prognosis [193,194,195,196]. A further implication of the reactivated developmental program is related to the splice variant of the insulin receptor, IR-A, which was originally reported to be highly expressed in fetal and cancer cells [77].…”

Section: Igf-ii Locus and Cancersupporting

confidence: 89%

The Neglected Insulin: IGF-II, a Metabolic Regulator with Implications for Diabetes, Obesity, and Cancer

Holly

Biernacka

Perks

2019

Cells

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When originally discovered, one of the initial observations was that, when all of the insulin peptide was depleted from serum, the vast majority of the insulin activity remained and this was due to a single additional peptide, IGF-II. The IGF-II gene is adjacent to the insulin gene, which is a result of gene duplication, but has evolved to be considerably more complicated. It was one of the first genes recognised to be imprinted and expressed in a parent-of-origin specific manner. The gene codes for IGF-II mRNA, but, in addition, also codes for antisense RNA, long non-coding RNA, and several micro RNA. Recent evidence suggests that each of these have important independent roles in metabolic regulation. It has also become clear that an alternatively spliced form of the insulin receptor may be the principle IGF-II receptor. These recent discoveries have important implications for metabolic disorders and also for cancer, for which there is renewed acknowledgement of the importance of metabolic reprogramming.

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Section: Igf-ii Locus and Cancersupporting

confidence: 89%

The Neglected Insulin: IGF-II, a Metabolic Regulator with Implications for Diabetes, Obesity, and Cancer

Holly

Biernacka

Perks

2019

Cells

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“…High insulin growth factor 2 (IGF2) expression is associated with chemotherapy resistance and is a candidate factor that could contribute to the worse treatment responses of Black compared with White patients with USC. Immunohistochemical analysis of 103 USC specimens found a higher IGF2 expression in Black compared with White patients, and a race-stratified multivariate analysis found that high IGF2 expression in the epithelial component of the tumors more than doubled the risk of death in Black women [ 81 ].…”

Section: Resultsmentioning

confidence: 99%

Histopathologic, Genetic and Molecular Characterization of Endometrial Cancer Racial Disparity

Javadian

Washington

Mukasa

et al. 2021

Cancers

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In contrast to the decline in incidence and mortality of most other cancers, these rates are rising for endometrial cancer. Black women with endometrial cancer have earlier diagnosis, more aggressive histology, advanced stage and worse outcomes compared with their White counterparts. Socioeconomic status, a higher incidence of aggressive histology, and comorbid conditions are known factors leading to racial disparity in patients with endometrial cancer; nevertheless, they do not account for the entire racial disparity; which emphasizes the roles of molecular, histopathological and genetic factors. We performed a comprehensive review of all published scientific literature up to January 2021 reporting histopathologic, genetic and molecular factors associated with racial disparities in patients with endometrial cancer. The interactions and pathways of molecules reported to have significant differential expression in endometrial cancers from Black and White patients were identified with Ingenuity Pathway Analysis. The majority of studies compared Black and White patients; however, limited data are available for other racial and ethnic groups. Reported differences that could account for the worse survival of Black endometrial cancer patients include more aggressive histopathologies and molecular alterations, including upregulation of molecules driving cell cycle progression, and p53 and HER2/NEU signaling. Several of these molecules are targeted by existing pharmaceuticals. These findings encourage further study and the development of race-specific treatment strategies.

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“…This reflects longstanding evidence that even after controlling for socioeconomic and pathologic characteristics, the black race is still associated with worse outcomes. 32 Existing literature has shown that certain cellular pathway proteins such as p53, HER2/Neu, and IGF2 exist in increased concentrations in black versus non-black patients and are associated with worse survival, [33][34][35] but additional poorly understood molecular mechanisms may be at play. Consequently, future studies should consider evaluating the molecular subtypes for black patients with locally advanced endometrial cancer focusing on microsatellite instability.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Racial Disparities on Outcome in Patients With Stage IIIC Endometrial Carcinoma

Patrich

Wang

Elshaikh³

et al. 2023

American Journal of Clinical Oncology

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Objective: To report the impact of race on clinical outcomes in patients with stage IIIC endometrial carcinoma. Materials and Methods: A retrospective multi-institutional study included 90 black and 568 non-black patients with stage IIIC endometrial carcinoma who received adjuvant chemotherapy and radiation treatments. Overall survival (OS) and recurrence-free survival (RFS) were calculated by the Kaplan-Meier method. Propensity score matching (PSM) was conducted. Statistical analyses were conducted using SPSS version 27. Results: The Median follow-up was 45.3 months. black patients were significantly older, had more nonendometrioid histology, grade 3 tumors, and were more likely to have >1 positive paraaortic lymph nodes compared with non-black patients (all P <0.0001). The 5-year estimated OS and RFS rates were 45% and 47% compared with 77% and 68% for black patients versus non-black patients, respectively (P <0.001). After PSM, the 2 groups were well-balanced for all prognostic covariates. The estimated hazard ratios of black versus non-black patients were 1.613 (P value=0.045) for OS and 1.487 (P value=0.116) for RFS. After PSM, black patients were more likely to receive the “Sandwich” approach and concurrent chemoradiotherapy compared with non-black (P=0.013) patients. Conclusions: Black patients have higher rates of nonendometrioid histology, grade 3 tumors, and number of involved paraaortic lymph nodes, worse OS, and RFS, and were more likely to receive the “Sandwich” approach compared with non-black patients. After PSM, black patients had worse OS with a nonsignificant trend in RFS. Access to care, equitable inclusion on randomized trials, and identification of genomic differences are warranted to help mitigate disparities.

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Insulin‐like growth factor 2: a poor prognostic biomarker linked to racial disparity in women with uterine carcinosarcoma

Cited by 6 publications

References 40 publications

The Neglected Insulin: IGF-II, a Metabolic Regulator with Implications for Diabetes, Obesity, and Cancer

The Neglected Insulin: IGF-II, a Metabolic Regulator with Implications for Diabetes, Obesity, and Cancer

Histopathologic, Genetic and Molecular Characterization of Endometrial Cancer Racial Disparity

The Impact of Racial Disparities on Outcome in Patients With Stage IIIC Endometrial Carcinoma

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