Abstract
The human HSP70 family is a type of heat shock protein (HSP), consisting of 13 members encoded by the HSPA genes. HSPs play important roles in regulating cellular responses and functions during carcinogenesis, but their relationship with colon cancer is unclear. In our study, we found that the expressions of HSPA1B, HSPA4, HSPA5, HSPA6, HSPA8, HSPA9, HSPA13, and HSPA14 were significantly increased, while those of HSPA1A, HSPA2, HSPA7, and HSPA12B were significantly decreased in colon cancer tissues. The expression of HSPA gene family members was associated with some clinicopathological characteristics, including age, gender, TNM stage, pathological stage, and CEA level. Furthermore, the Kaplan–Meier method and Cox regression analysis showed that high HSPA1A, HSPA1B, and HSPA7 expressions were related to unfavorable survival, and high HSPA9 was associated with favorable survival. The relationships between HSPA1A and HSPA9 expression and survival were validated in the GEO dataset, and the HSPA1A and HSPA9 protein expression differences between colon cancer tissues and normal tissues were validated in the UALCAN database. Methylation of HSPA1A and HSPA9 was also analyzed, and it was found that the methylation of the HSPA1A promoter was significantly increased, and the methylation of the HSPA9 promoter was significantly decreased in colon cancer tissues. Increasing the methylation level of the HSPA1A gene and decreasing the methylation level of HSPA9 were related to favorable prognosis. The expression difference of HSPA1A/HSPA1B/HSPA7/HSPA9 was verified in colon cancer cell lines and colonic epithelial cells. Gene ontology analysis was used to screen signal pathways related to HSPA1A-, HSPA1B-, HSPA7-, and HSPA9- high phenotype. In summary, the increased expressions of HSPA1A1, HSPA1B, and HSPA7 were associated with poor prognosis, while that of HSPA9 was related to favorable prognosis for colon cancer patients.
Highlights
Colon cancer is one of the most common malignant tumors in the world
Results showed that the expression level of HSPA1A and HSPA1B increased as the pathologic stage increased (Figure 2G)
Logistic regression showed that increased HSPA1A, HSPA1B, HSPA5, and HSPA6 were significantly related to the increased disease stage, and increased HSPA8 was related to the decreased stage of the disease
Summary
There were about 18.1 million new cancer cases and 9.6 million cancer-related deaths in 2018. Among all types of cancers, colon cancer ranks third in terms of incidence (1,096,601 new cases) and fourth in mortality (551,269 deaths) [1]. About 30% of the patients develop local recurrence or distant metastasis after curative therapy [2]. For these patients, system therapy is the recommended therapy. The treatment efficacy has been improved in the past few years, the prognosis of patients with advanced or recurrent colon cancer is still poor, with an overall survival interval of 13– 17 months [3]. It is an urgent need to discover new biomarkers with prognostic and therapeutic value
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