Histone methyltransferase KMT5A gene modulates oncogenesis and lipid metabolism of papillary thyroid cancer inï¿½vitro

Abstract Purpose Lipid metabolism plays important roles not only in the structural basis and energy supply of healthy cells but also in the oncogenesis and progression of cancer. In this study, we investigate the prognostic value of lipid metabolism related genes in papillary thyroid cancer (PTC). Methods The in time to recurrence predictive gene signature was developed, internally and externally validated based on PTC datasets including The Cancer Genome Atlas (TCGA) and GSE33630 datasets. Univariate, LASSO and multivariate Cox regression analysis were applied to assess prognostic genes and build the prognostic gene signature. The expression profiles of prognostic genes were further determined by immunohistochemistry by using in-house cohorts which enrolled 97 patients. Kaplan-Meier curve, time-dependent receiver operating characteristic curve, nomogram and decision curve analysis were used to assess the performance of the gene signature. Results We identified four recurrence-related genes, PDZK1IP1, TMC3, LRP2 and KCNJ13, and established a 4-gene signature recurrence risk model. The expression profile of the 4 genes in the TCGA and in-house cohort indicated that stage T1/T2 PTC and locally advanced PTC exhibited notable associations not only with clinicopathological parameters but also with recurrence. Calibration analysis plots indicated the excellent predictive performance of the prognostic nomogram constructed based on the gene signature. GSEA showed that high-risk cases exhibited changes in several important tumorigenesis-related pathways, such as the intestinal immune network and the p53 and Hedgehog signalling pathways. Conclusion Our findings indicate that lipid metabolism-related gene profiling represents a potential marker for prognosis and treatment decisions for PTC patients.

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Apolipoprotein A1 is A Protective Factor for Male Papillary Thyroid Cancer Patients. A Cross-Sectional Study of Single Academic Center in China.

10.21203/rs.3.rs-34976/v1 ◽

2020 ◽

Author(s):

Maoguang Ma ◽

Mingdian Wang ◽

Zhanqiang Zhang ◽

Bo Lin ◽

Zicheng Sun ◽

...

Keyword(s):

Thyroid Cancer ◽

Lipid Metabolism ◽

Papillary Thyroid Cancer ◽

Tumor Size ◽

Serum Lipid ◽

Common Type ◽

Female Group ◽

Papillary Thyroid ◽

Apo B ◽

Apo E

Abstract Background: Papillary thyroid cancer (PTC) is the most common type of thyroid cancer and the incidence of PTC has continued to increase over the past decades. Many studies have shown that obesity is an independent risk factor for PTC and obese PTC patients tend to have a relative larger tumor size and higher grade of tumor stage. Obesity is associated with disordered lipid metabolism and the relationship between serum lipids and PTC remains unclear. Therefore, this study aimed to investigate the association between serum lipid level and PTC.Methods: We retrospectively analyzed 1018 PTC patients diagnosed and treated in our hospital, all these cases were first diagnosed with PTC and had complete clinical information including ultrasound reports before surgery, serum lipid (CHOL, TG, HDL-c, LDL-c, Apo-A1, Apo-B, Apo-E) results, surgical records and pathological reports. Results: None of these lipid markers were associated with tumor size in the whole cohort and in the female group. In the male group, on crude analysis, Apo-A1 showed a marginally significant association with tumor size, [OR=0.158 (0.021-1.777)], p=0.072. After adjusting for age and multifocality, Apo-A1 showed a significant association with tumor size [OR=0.126 (0.016-0.974)], p=0.047. This association become more apparent in a young male subgroup, [OR=0.051 (0.005-0.497)], p=0.009. CHOL, TG, HDL-c, LDL-c, Apo-B, Apo-E did not show significant association with tumor size. As for LNM, neither in the male group nor in the female group were found to be associated with any serum lipid biomarkers.Conclusion: As PTC incidences continues to increase, our finding a negative association between PTC and apoA-1 imply that these lipids are protective factors for male PTC patients and provide us new clues about PTC and lipid metabolism, which may contribute to further investigation concerning diagnosing and preventing this most common type of thyroid cancer.

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