Local and Systemic Interleukin-32 in Esophageal, Gastric, and Colorectal Cancers: Clinical and Diagnostic Significance.

Dorota Diakowska,Małgorzata Krzystek-Korpacka

doi:10.3390/diagnostics10100785

Dorota Diakowska, Małgorzata Krzystek-Korpacka

Open Access

https://doi.org/10.3390/diagnostics10100785

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Journal: Diagnostics (Basel, Switzerland)	Publication Date: Oct 4, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: Wroclaw Medical University

Abstract

Little is known on clinical and diagnostic relevance of interleukin-32 in gastrointestinal tract (GIT) cancers. We determined its mRNA (n = 52) and protein (n = 63) expression in paired (tumor-normal) samples from esophageal squamous cell carcinoma (ESCC) and gastric (GC) and colorectal cancer (CRC) patients, with reference to cancer-associated genes, and quantified circulating interleukin-32 in 70 cancer patients and 28 controls. IL32 expression was significantly upregulated solely in ESCC, reflecting T stage in non-transformed tumor-adjacent tissue. Fold-change in IL32 and IL-32 was higher in left-sided CRC, owing to high interleukin expression in non-transformed right-sided colonic mucosa. IL32 was independently and positively associated with Ki67, HIF1A, and ACTA2 and negatively with TJP1 in tumors and with IL10Ra and BCLxL in non-transformed tumor-adjacent tissue. IL-32 protein was significantly upregulated in colorectal tumors. In ESCC, advanced stage and lymph node metastasis were associated with significant IL-32 upregulation. Circulating interleukin was significantly elevated in cancer patients, more so in ESCC and GC than CRC. As biomarker, IL-32 detected gastroesophageal cancers with 99.5% accuracy. In conclusion, IL-32 is upregulated in GIT cancers at local and systemic level, reflecting hypoxia and proliferative and invasive/metastatic capacity in tumors and immunosuppressive and antiapoptotic potential in non-transformed mucosa, while being an accurate biomarker of gastroesophageal cancers.

Highlights

Gastrointestinal tract (GIT) cancers, encompassing adenocarcinomas of the colorectum (CRC) and stomach (GC) and esophageal squamous cell carcinoma (ESCC), are the most common and deadliest malignancies [1]
Relative IL32 expression was determined in patient-matched samples from tumor and non-transformed mucosa adjacent to tumor (52 pairs), obtained from 17 patients with ESCC, 14 with GC, and 21 with CRC using reverse-transcribed quantitative polymerase chain reaction (RT-Quantitative (real-time) polymerase chain reaction (qPCR))
Despite growing interest in IL-32, there is a scarcity of data concerning its status in the GIT cancers while its diagnostic utility has not been previously determined

Summary

Introduction

Gastrointestinal tract (GIT) cancers, encompassing adenocarcinomas of the colorectum (CRC) and stomach (GC) and esophageal squamous cell carcinoma (ESCC), are the most common and deadliest malignancies [1]. The GIT cancers, ESCC and GC in particular, are frequently diagnosed when advanced, rendering them non-amenable for curative resection. Available therapeutic options fail to improve outcomes for patients with gross metastatic disease and cancers resistant to chemo- and radiotherapy [2,3,4,5]. There is a growing awareness that in order to improve prognosis, a better understanding of cancer-associated abnormalities at molecular level is urgently needed to facilitate biomarker discovery and develop and implement patient-tailored approach, referred to as “precision medicine” [6,7,8,9]

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