Gender differences in hepatocellular cancer: disparities in nonalcoholic fatty liver disease/steatohepatitis and liver transplantation

Wu, Enboa; Wong, Linda L.; Hernandez, Brenda Y.; Ji, Junfang; Wang, Jia; Kwee, Sandi A.; Kalathil, Sumodh

doi:10.20517/2394-5079.2018.87

Cited by 109 publications

(103 citation statements)

References 40 publications

(37 reference statements)

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“…Our findings contrast with those of Ladenheim 10 and Wu, 11 who found female sex was not associated with mortality in HCC patients. There are differences between these study populations and ours that may explain this discrepancy, including demographics, liver disease aetiologies and degree of liver dysfunction.…”

Section: Discussioncontrasting

confidence: 99%

Sex disparities in presentation and prognosis of 1110 patients with hepatocellular carcinoma

Rich

Murphy

Yopp

et al. 2020

Aliment Pharmacol Ther

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Summary Background Although sex disparities in hepatocellular carcinoma (HCC) incidence have been well described, there are limited data examining sex disparities in HCC prognosis. Aim To characterise sex differences in HCC presentation and prognosis. Methods We performed a retrospective study of consecutive patients (n = 1110, 23.5% women) diagnosed with HCC between 2008 and 2017 at two US health systems. We used Cox proportional hazard and multivariable logistic regression models to identify factors associated with overall survival, early tumour detection and response to HCC treatment (per the modified Response Evaluation Criteria in Solid Tumors [mRECIST] criteria). Results Women were older at HCC diagnosis (mean 62.5 vs 59.2 years, P < 0.001) and had a higher proportion of early‐stage tumours (53.1% vs 43.7% Barcelona Clinic Liver Cancer [BCLC] stage 0/A, P = 0.04), but similar liver function compared to men (49.2% vs 47.1% Child Pugh A, P = 0.27). In univariable analysis, women had significantly better overall survival than men (median 17.1 vs 12.0 months, P = 0.02). When stratified by age, younger (<65 years) women had better overall survival than men (18.3 vs 11.2 months, P = 0.02); however, older (≥65 years) women and men had similar overall survival (15.5 vs 15.7 months, P = 0.45). In multivariable analysis, female sex was independently associated with lower mortality after adjusting for age, race/ethnicity, alpha‐fetoprotein, BCLC stage, Albumin‐Bilirubin grade and Child Pugh score (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.68‐0.98). In secondary analyses, female sex was independently associated with early tumour detection (odds ratio [OR] 1.46, 95% CI 1.05‐2.02) and response to first HCC treatment (OR 1.72, 95% CI 1.18‐2.53) after adjusting for the same covariates. Conclusion In a large cohort of patients with HCC, women had significantly better prognosis than men.

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Section: Discussioncontrasting

confidence: 99%

Sex disparities in presentation and prognosis of 1110 patients with hepatocellular carcinoma

Rich

Murphy

Yopp

et al. 2020

Aliment Pharmacol Ther

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“…As commonly observed [37][38][39], HCC cases were dominated by men, with only 26% of the cases presented by women (Table 2). Single focal lesions represented 65% of the cases, and lesions <5 cm in size represented 83% of the cases.…”

Section: Characteristics Of Subjectssupporting

confidence: 71%

Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

Ismail

Fiehn

Elfert

et al. 2020

Cancers

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The major risk factors for hepatocellular carcinoma (HCC) are hepatitis C and B viral infections that proceed to Chronic Liver Disease (CLD). Yet, the early diagnosis and treatment of HCC are challenging because the pathogenesis of HCC is not fully defined. To better understand the onset and development of HCC, untargeted GC-TOF MS metabolomics data were acquired from resected human HCC tissues and their paired non-tumor hepatic tissues (n = 46). Blood samples of the same HCC subjects (n = 23) were compared to CLD (n = 15) and healthy control (n = 15) blood samples. The participants were recruited from the National Liver Institute in Egypt. The GC-TOF MS data yielded 194 structurally annotated compounds. The most strikingly significant alteration was found for the class of sugar alcohols that were up-regulated in blood of HCC patients compared to CLD subjects (p < 2.4 × 10−12) and CLD compared to healthy controls (p = 4.1 × 10−7). In HCC tissues, sugar alcohols were the most significant (p < 1 × 10−6) class differentiating resected HCC tissues from non-malignant hepatic tissues for all HCC patients. Alteration of sugar alcohol levels in liver tissues also defined early-stage HCC from their paired non-malignant hepatic tissues (p = 2.7 × 10−6). In blood, sugar alcohols differentiated HCC from CLD subjects with an ROC-curve of 0.875 compared to 0.685 for the classic HCC biomarker alpha-fetoprotein. Blood sugar alcohol levels steadily increased from healthy controls to CLD to early stages of HCC and finally, to late-stage HCC patients. The increase in sugar alcohol levels indicates a role of aldo-keto reductases in the pathogenesis of HCC, possibly opening novel diagnostic and therapeutic options after in-depth validation.

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“…These diseases were also found to be associated with proteins that were highly expressed in X spermatozoa (Figure 2). Similarly, abundant proteins in Y spermatozoa, that is TUBA8 and GSTM3, were found to be associated with hepatic cancer and renal cancer, respectively, and the prevalence of both diseases were reported to be high in men compared to the women (Woldrich et al, 2008;Wu et al, 2018). However, few other diseases that are found to be related with the differentially expressed proteins either in the X and Y spermatozoa represent different results compared to the epidemiological data (Figure 3).…”

Section: Genomic and Proteomic Contents Of X And Y Spermatozoamentioning

confidence: 89%

New Biological Insights on X and Y Chromosome-Bearing Spermatozoa

Rahman

Pang

2020

Front. Cell Dev. Biol.

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A spermatozoon is a male germ cell capable of fertilizing an oocyte and carries genetic information for determining the sex of the offspring. It comprises autosomes and an X (X spermatozoa) or a Y chromosome (Y spermatozoa). The origin and maturation of both X and Y spermatozoa are the same, however, certain differences may exist. Previous studies proposed a substantial difference between X and Y spermatozoa, however, recent studies suggest negligible or no differences between these spermatozoa with respect to ratio, shape and size, motility and swimming pattern, strength, electric charge, pH, stress response, and aneuploidy. The only difference between X and Y spermatozoa lies in their DNA content. Moreover, recent proteomic and genomic studies have identified a set of proteins and genes that are differentially expressed between X and Y spermatozoa. Therefore, the difference in DNA content might be responsible for the differential expression of certain genes and proteins between these cells. In this review, we have compiled our present knowledge to compare X and Y spermatozoa with respect to their structural, functional, and molecular features. In addition, we have highlighted several areas that could be explored in future studies in this field.

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Gender differences in hepatocellular cancer: disparities in nonalcoholic fatty liver disease/steatohepatitis and liver transplantation

Cited by 109 publications

References 40 publications

Sex disparities in presentation and prognosis of 1110 patients with hepatocellular carcinoma

Sex disparities in presentation and prognosis of 1110 patients with hepatocellular carcinoma

Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

New Biological Insights on X and Y Chromosome-Bearing Spermatozoa

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