Hongkai Zhuang1,2, Xinming Chen3, Ying Wang4, Shanzhou Huang2, Bo Chen5, Chuanzhao Zhang6, Baohua Hou7. 1. Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510080, China. 2. Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Er Road, Guangzhou, 510080, China. 3. Department of Hepatobiliary Surgery, Shenshan Central Hospital, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Shanwei, 516600, China. 4. The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, 310006, China. 5. Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Er Road, Guangzhou, 510080, China. chenbo@gdph.org.cn. 6. Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Er Road, Guangzhou, 510080, China. 641703837@qq.com. 7. Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Er Road, Guangzhou, 510080, China. 15917919681@163.com.
Abstract
BACKGROUND: It is widely considered that pancreatic cancer (PC) is an immunosuppressive cancer. Immune-based therapies remain promising therapeutic strategies for PC. Overexpression of lipase H (LIPH) was reported to be related to immunity in cattle and has also been demonstrated to promote tumor progression in several tumors, but its role in pancreatic carcinogenesis remains unclear. Study on LIPH in PC might provide a new insight into the immunosuppression in PC. METHODS: The potential biological and clinical significance of LIPH was evaluated by bioinformatics analysis. We further investigated potential associations between the expression of LIPH and tumor immune infiltration using the CIBERSORT algorithm, the ESTIMAT algorithm, and single sample gene set enrichment analysis (ssGSEA). RESULTS: LIPH was significantly overexpressed in tumor tissues compared with normal tissues. LIPH overexpression correlated with tumor recurrence, advanced histologic grade, and poorer overall survival (OS). Four of the most common somatic mutation, including KRAS, TP53, CDKN2A, and SMAD4, in PC were all correlated with high LIPH expression. And high LIPH expression was significantly correlated with KRAS activation and SMAD4 inactivation. Besides, LIPH expression was involved in various biological pathways such as negative regulation of cell-cell adhesion, actin cytoskeleton, EMT, angiogenesis, and signaling by MST1. And LIPH overexpression caused high infiltration of TAMs, Treg cells, and Th2/Th1, but reduced the infiltration of CD8+ T cells and Th1 cells. CONCLUSIONS: Our findings demonstrated that LIPH correlated with immune suppression or evasion and may function as a novel unfavorable prognostic biomarker in PC.
BACKGROUND: It is widely considered that pancreatic cancer (PC) is an immunosuppressive cancer. Immune-based therapies remain promising therapeutic strategies for PC. Overexpression of lipase H (LIPH) was reported to be related to immunity in cattle and has also been demonstrated to promote tumor progression in several tumors, but its role in pancreatic carcinogenesis remains unclear. Study on LIPH in PC might provide a new insight into the immunosuppression in PC. METHODS: The potential biological and clinical significance of LIPH was evaluated by bioinformatics analysis. We further investigated potential associations between the expression of LIPH and tumor immune infiltration using the CIBERSORT algorithm, the ESTIMAT algorithm, and single sample gene set enrichment analysis (ssGSEA). RESULTS: LIPH was significantly overexpressed in tumor tissues compared with normal tissues. LIPH overexpression correlated with tumor recurrence, advanced histologic grade, and poorer overall survival (OS). Four of the most common somatic mutation, including KRAS, TP53, CDKN2A, and SMAD4, in PC were all correlated with high LIPH expression. And high LIPH expression was significantly correlated with KRAS activation and SMAD4 inactivation. Besides, LIPH expression was involved in various biological pathways such as negative regulation of cell-cell adhesion, actin cytoskeleton, EMT, angiogenesis, and signaling by MST1. And LIPH overexpression caused high infiltration of TAMs, Treg cells, and Th2/Th1, but reduced the infiltration of CD8+ T cells and Th1 cells. CONCLUSIONS: Our findings demonstrated that LIPH correlated with immune suppression or evasion and may function as a novel unfavorable prognostic biomarker in PC.
Authors: Alexandr V Bazhin; Ivan Shevchenko; Viktor Umansky; Jens Werner; Svetlana Karakhanova Journal: Cancer Immunol Immunother Date: 2013-10-16 Impact factor: 6.968
Authors: Maartje G Schouwenburg; Karijn P M Suijkerbuijk; Rutger H T Koornstra; Anouk Jochems; Michiel C T van Zeijl; Alfons J M van den Eertwegh; John B A G Haanen; Maureen Jb Aarts; Alexander C J van Akkooi; Franchette W P J van den Berkmortel; Jan Willem B de Groot; Geke A P Hospers; Ellen Kapiteijn; Wim H Kruit; Djura Piersma; Rozemarijn S van Rijn; Albert J Ten Tije; Gerard Vreugdenhil; Jacobus J M van der Hoeven; Michel W J M Wouters Journal: Cancers (Basel) Date: 2019-12-04 Impact factor: 6.639