Clinicopathological significance of cystatin A expression in progression of esophageal squamous cell carcinoma

Abstract

We previously conducted transcriptome analysis of a paired specimen of normal and esophageal squamous cell carcinoma (ESCC) tissues and found that mRNA expression of cystatin A (CSTA), a member of the cystatin superfamily, was perturbed in tumors compared with that in the background mucosa. However, little is known about the significance of CSTA expression in ESCC.The mRNA expression of CSTA was evaluated by qRT-PCR using 28 paired frozen samples of tumor and nontumor mucosae. The protein expression of CSTA was evaluated by the immunostaining of formalin-fixed, paraffin-embedded sections of ESCC samples from 59 patients who underwent surgery, and its relationship with clinical features was analyzed.The mRNA expression of CSTA was significantly decreased in ESCC compared with that in matched normal mucosa (P < .0001). The protein expression of CSTA was limited in stratum granulosum and stratum spinosum but not in stratum basal in normal esophageal mucosa. It was reduced in all ESCC tissue samples compared with normal tissues; however, CSTA expression levels in tumors showed considerable variation. Of the 59 samples, 20 did not express CSTA, whereas 39 clearly expressed it. The expression of CSTA in tumors was significantly associated with pT classification (deeper tumor invasions) (P = .0118) and advanced TNM stages (P = .0497). In CSTA-positive tumor samples, CSTA-expressing cancer cells often expressed Ki67, a proliferation marker, which was in sharp contrast to normal mucosa, where Ki67-expressing cells were limited to the basal layer and did not express CSTA. Furthermore, CSTA expression was observed in all 22 lymph node metastases analyzed.Relatively high levels of CSTA expression in tumors were correlated with tumor progression and advanced cancer stage, including lymph node metastasis.

Identification of CD37, cystatin A, and IL-23A gene expression in association with brain metastasis: analysis of a prospective trial

“…We found a significant downregulation of IL-23 to be associated with BM; however, it is possible that similar to the results found by Shiba et al, 13 mRNA expression could be significantly decreased overall but still have areas within the tumor showing increased expression. Again, this suggests that further studies investigating the immunostaining of tumor samples may be beneficial.…”

“…11 Studies have also indicated that CSTA suppressed ultraviolet-induced apoptosis in keratinocytes by the inhibition of caspase 3. 12 A recent study in 2018 by Shiba et al 13 showed that the mRNA expression of CSTA was significantly decreased in esophageal squamous cell carcinoma with a P <0.001; however, some portions of the tumor tissues showed high CSTA expression levels, and these areas showed the most advanced tumor invasion. The authors felt that although a significant portion of cells in the tumor were attempting to downregulate CSTA, the cells unable to do so had advanced tumor progression.…”

RETRACTED: Silencing lncRNAs PVT1 Upregulates miR-145 and Confers Inhibitory Effects on Viability, Invasion, and Migration in EC

“…Esophageal carcinoma (EC) is a common malignant gastrointestinal tumor and one of the main reasons for tumor-related death. 1 It has been estimated that in 2012, 455,800 patients were newly diagnosed with EC and 400,200 EC-related deaths occurred globally. 2 Smoking, drinking, and high body mass index are the risk factors for EC, and it has been validated that the ingestion of vegetables and fruits can reduce the morbidity of EC.…”

Investigation of the clinical significance and prospective molecular mechanisms of cystatin genes in patients with hepatitis B virus‑related hepatocellular carcinoma

“…Therefore, CSTs may also be associated with tumor progression. Notably, CSTs have been reported to be associated with the progression of various types of cancer, including bladder cancer (40), breast cancer (41,42), esophageal cancer (43), ovarian cancer (44) and prostate cancer (45). The results of GSEA in the present study indicated that CST7 was significantly enriched in liver cancer progression.…”