Original ArticleIncreased Expression of LIPC Is Associated with Aggressive Phenotype of Borrmann Type 4 Gastric Cancer
Introduction
Gastric cancer is the fourth most common malignancy worldwide.1 About one million new cases of gastric cancer occur in the world each year, and the majority are advanced gastric cancer.2 Borrmann type 4 (diffusely infiltrating) gastric cancer is a special type of advanced gastric cancer with extremely high malignancy and poor prognosis.3,4 Clinically, Borrmann type 4 gastric cancer often involves the whole layer of the gastric wall and spreads to the whole stomach, accompanied by extensive lymph node metastasis and peritoneal metastasis.5 With progress in the treatment of gastric cancer, survival in advanced gastric cancer has improved, but therapeutic effect in Borrmann type 4 gastric cancer has not improved significantly.6 Therefore, identification of novel prognostic and predictive markers is important to find potential therapeutic targets in Borrmann type 4 gastric cancer.
The correlation between lipid metabolism and cancer has recently been determined.7,8 Lipid metabolism dysfunction is widespread in cancer cells, and abnormal lipid metabolism is involved in the regulation of various biological behaviors of cancer cells.9–11 Lipase C hepatic type (LIPC) is a member of the lipase family, whose gene is located on human chromosome 15, with a total length of 35 kb, containing 9 exons and 8 introns, and encoding a 65-kD glycoprotein.12 LIPC plays an important role in lipoprotein metabolism, and abnormal expression of LIPC is correlated with metabolic diseases and circulatory system diseases.13,14 In recent years, several studies have indicated a potential role for LIPC in the progression of cancers. In non-small cell lung cancer, LIPC expression level in tumor cells was shown to be an independent factor predicting patients’ prognosis, where patients with low LIPC expression could benefit from platinum-based chemotherapy.15 In regard to colorectal cancer, LIPC promoted liver metastasis in an orthotopic mouse model of colorectal cancer, and high LIPC expression predicted hepatic metastasis in patients.16 Nevertheless, to date, the expression of LIPC in Borrmann type 4 gastric cancer and its biological role in its progression is unknown.
Therefore, we carried out the current study to investigate LIPC expression in Borrmann type 4 gastric cancer and its correlation with clinicopathological features and prognosis. The biological roles of LIPC in Borrmann type 4 gastric cancer progression were also investigated.
Section snippets
Tissue Samples and Follow-Up
A total of 324 patients who were treated by total or subtotal gastrectomy with lymphadenectomy for primary gastric cancer between March 2009 and June 2012 at the First Affiliated Hospital of China Medical University were selected for this study. All patient-derived specimens were collected and archived under protocols approved by the Institutional Review Boards of the First Affiliated Hospital. No patients had received neoadjuvant therapy. The group was composed of 229 men and 95 women with a
LIPC Is Upregulated in Human Gastric Cancer Tissues, Especially in Borrmann Type 4 Gastric Cancer Tissues
LIPC was expressed in both matched adjacent non-tumor tissues and primary gastric cancer tissues, where LIPC expression was detected in the cytoplasm. Representative micrographs of LIPC staining are shown in Fig. 1. In adjacent non-tumor tissues, high LIPC expression was detected in only 8 (4.5%) cases and low in 170 (95.5%) cases. Conversely, in gastric cancer tissues, high expression of LIPC was observed in 108 (33.3%) cases and low in 216 (66.7%) cases. The difference in LIPC expression
Discussion
The malignant degree of Borrmann type 4 gastric cancer is the highest and the therapeutic effect is the worst in gastric cancer.4 Unfortunately, little is known at present about molecular markers in predicting risk of Borrmann type 4 gastric cancer progression. The present study determined for the first time LIPC expression and its correlation with clinicopathological features and patient survival in gastric cancer, especially in Borrmann type 4 gastric cancer. We demonstrated that LIPC
Conclusions
In conclusion, this study is the first to report that high expression of LIPC is an independent prognostic factor for poor survival and correlates with enhanced tumor aggressiveness in Borrmann type 4 gastric cancer. Moreover, our data demonstrate that LIPC plays a role in the regulation of Borrmann type 4 gastric cancer cell migration and invasion. Further studies are needed to clarify whether LIPC is involved in EMT in Borrmann type 4 gastric cancer.
Authors’ Contribution
Hui-mian Xu and Jin-yu Huang were involved in the study concept and design and in writing the article; Jin-yu Huang, Wei-lan Zhang, Ya-nan Xing, Ying-ying Xu, and Zhi Zhu were involved in the analysis and interpretation of data; Wei-lan Zhang, Yu-en Tan, Zhen-ning Wang, Wen-bin Hou, and Song-cheng Yin were involved in the data collection and cell experiment.
Funding Information
This work was supported by National Science Foundation of China (No.81602522, No. 81372550).
Conflict of Interest
The authors declare that they have no conflict of interest.
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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