Identification of CKS1B as a prognostic indicator and a predictive marker for immunotherapy in pancreatic cancer

Abstract

As a regulatory subunit of cyclin kinase, CKS1B promotes cancer development and is associated with poor prognosis in multiple cancer patients. However, the intrinsic role of CKS1B in pancreatic cancer remains elusive. In our research, CKS1B expression in pancreatic tumor tissue was higher than that in normal tissue by TCGA, Oncomine and CPTAC databases analysis. Similar result was verified in our center tissues by qRT-PCR. CKS1B expression was closely relevant to histologic grading, prognosis, and TMB. GSEA showed that CKS1B mainly participated in the regulation of autophagy and T cell receptor signaling pathway. Furthermore, CIBERSORT analysis showed that there was a strong correlation between CKS1B expression and tumor immune cells infiltration. Drug sensitivity analysis showed that patients with high CKS1B expression appeared to be more sensitive to gemcitabine, 5-fluorouracil, and paclitaxel. We then investigated cell viability and migratory ability by CCK8 and transwell assay, respectively. Results indicated that CKS1B knockdown by short hairpin RNA significantly reduced pancreatic cancer cell viability and invasion via regulating PD-L1 expression. In conclusion, our research further demonstrates the role of CKS1B in pancreatic cancer and the signaling pathways involved. The association of CKS1B with immune infiltration and immune checkpoint may provide a new direction for immunotherapy of pancreatic cancer.

Deciphering lung adenocarcinoma prognosis and immunotherapy response through an AI‐driven stemness‐related gene signature

“…Li and colleagues found that CKS1B expression in pancreatic tumour tissues was higher than in normal tissues, and this result was validated by reverse transcription‐quantitative polymerase chain reaction. Moreover, immune infiltration analysis revealed that CKS1B expression was significantly associated with the level of immune cell infiltration in pancreatic cancer, and knockdown experiments showed a strong correlation between CKS1B and the cell activity and invasiveness of pancreatic cancer 54 . A predictive model developed by Mohamad and others, based on five genes including CKS1B, CCT2, PRKDC, NONO, and UBE2A, successfully predicted the prognosis of patients with multiple myeloma and has been validated in several independent datasets.…”

“…Moreover, immune infiltration analysis revealed that CKS1B expression was significantly associated with the level of immune cell infiltration in pancreatic cancer, and knockdown experiments showed a strong correlation between CKS1B and the cell activity and invasiveness of pancreatic cancer. 54 A predictive model developed by Mohamad and others, based on five genes including CKS1B, CCT2, PRKDC, NONO, and UBE2A, successfully predicted the prognosis of patients with multiple myeloma and has been validated in several independent datasets. These results suggest that CKS1B could play a crucial role in the development of malignant tumour.…”

CKS1B promotes the growth of ovarian cancer cells by regulating the expression of PD-L1

“…Ovarian cancer is becoming increasingly prevalent each year and has a high mortality rate. CKS1B has been previously identified as a crucial target in tumorigenesis, including pancreatic cancer [12], glioma [14] and myeloma [15]. However, the association between CKS1B and ovarian cancer has yet to be elucidated.…”

“…The inhibition of CKS1B has been shown to attenuate cell proliferation and migration in colorectal carcinoma (31717435) while suppressing CKS1B has been demonstrated to inhibit gastric cancer cell proliferation (29283424). Reducing CKS1B in pancreatic cancer cells has been demonstrated to markedly lower cell viability and invasion through the modulation of PD-L1 expression [12]. Moreover, in papillary thyroid carcinoma cells, CKS1B has been found to promote proliferation and invasion by activating the signal transducer and activator of transcription 3 (STAT3)/PD-L1 and phosphorylated protein kinase B (Akt) signaling pathways [13].…”