LUSC is the second most common lung malignancy in the world, accounting for 20–30% of non-small cell lung cancer cases and causing approximately 400,000 deaths worldwide each year. LUSC has a low cure rate, with a 5-year survival rate of 18%. The treatment for LUSC mainly includes surgery and chemoradiotherapy, the efficacy for advanced patients is limited, and early diagnosis and treatment are effective ways to improve the survival status of LUSC patients. Compared with lung adenocarcinoma, LUSC has a poor clinical prognosis and lacks targeted drugs. DHX32 is a helicase in the DHX family. The expression level of DHX32 can be found in the tissues of colorectal cancer, breast cancer, and liver cancer, which is higher than that of the adjacent tissues, and can promote the proliferation, migration, and invasion of cancer cells, which is related to the prognosis of patients. However, most studies on DHX32 focus on liver cancer, and there are few studies on LUSC, especially on diagnosis and prognosis.
The results of this study showed that DHX32 was up-regulated in LUSC tissues, which was the same as the expression of colorectal cancer and liver cancer, and the opposite of acute lymphoblastic leukemia. The expression level of DHX32 in the LUSC sample group was significantly higher than that in the control group, and the survival rate of the high expression group was significantly higher than that of the low expression group, indicating that DHX32 has diagnostic value. This is similar to the prognostic and diagnostic role of DHX32 in breast cancer[12].
The Willcoxon hypothesis showed that the infiltration of two kinds of immune cells (Mast cells resting and T cells CD4 naive) in the high-expression group was significantly lower than that in the low-expression group. Mast cells influence the occurrence and development of tumors by promoting inflammation, promoting angiogenesis, regulating immune response, and promoting tumor invasion and metastasis. CD4+T cells influence tumor development through immunomodulatory effects.
Based on the expression levels of immune checkpoint inhibitors PD-1, PD-L1, and CTLA-4 in LUSC, we analyzed the differences between the high and low expression groups, and the results showed that CTLA-4 and PD-1 immune checkpoint inhibitors had significant differences between the high and low expression groups. CTLA-4 mainly inhibits the activation and proliferation of T cells, thereby reducing the body's ability to attack tumor cells. PD-1 mainly inhibits the killing function of T cells, so that tumor cells can evade immune surveillance.
In this study, 347 differential genes were screened based on the expression level of DHX32. Univariate Cox regression analysis was used to obtain 11 genes significantly associated with survival. Multivariate Cox regression analysis was used to screen out CLDN11, PID1, MAMDC2, and three prognostic genes. CLDN11 is a tight-linking protein that is abnormally expressed in many tumors. The abnormal expression of CLDN11 can promote the proliferation, invasion, and metastasis of tumor cells. For example, in breast cancer, high expression of CLDN11 is closely related to tumor malignancy and prognosis[13]. PID1 plays an important role in cell division and apoptosis. No studies have shown that PID1 is directly involved in the development and development of cancer. MAMDC2 is a coding protein, that is abnormally expressed or mutated in many cancers and has cancer inhibition, cell migration and invasion, cell cycle regulation, and interaction with microtubule-associated proteins in the occurrence and development of cancer. These three independent prognostic genes also play a critical role in LUSC and are expected to be new targets for LUSC.
Through correlation analysis between risk score and clinical features, this study found that risk score, age, and gender were correlated with risk score. Univariate Cox regression analysis found that risk score and age were significantly correlated with survival; multivariate Cox regression screened out an independent prognostic factor for risk score, and the study found that risk score was negatively correlated with tumor survival. The lower the risk score, the higher the overall survival probability of 1, 3, and 5 years.
The five enrichment pathways in this study have been reported to be closely related to the prognosis of low-grade glioma [14], female reproductive tract tumor[15], lung cancer[16] and liver cancer[17], respectively. They regulate the occurrence and development of cancer through immune surveillance and escape mechanisms, inflammatory response, promotion of new angiogenesis, and intercellular interactions.
This research shows that there are five kinds of drug sensitivity with significant differences, respectively Bosutinib, Docetaxel, Gefitinib and Erlotinib, and Lapatinib. The difference between EGFR and BCR in the target genes of these drugs was significant in high and low-risk groups. Bosutinib is a tyrosine kinase inhibitor that targets receptor tyrosine kinases such as BCR-ABL, KIT, and PDGFR. By inhibiting the activity of these receptors, it blocks the growth and proliferation signal transduction of tumor cells, thus inhibiting tumor growth[18]. Docetaxel belongs to a class of drugs called paclitaxel, which primarily prevents cell division by inhibiting the dynamic stability of tubulin. It causes tubulin to polymerize into clumped structures, causing cells to fail to form normal spindles during mitosis, thus preventing tumor cells from dividing and proliferating[19]. Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. It inhibits the growth and proliferation of tumor cells by selectively inhibiting the tyrosine kinase activity of EGFR and blocking EGFR signaling[20]. Erlotinib is also an EGFR tyrosine kinase inhibitor, similar to Gefitinib, but more selective to EGFR. It inhibits the growth and proliferation of tumor cells by inhibiting the activity of EGFR and blocking EGFR signaling[21]. Lapatinib is a multi-target tyrosine kinase inhibitor that simultaneously inhibits EGFR and other receptors such as HER2 and VEGFR. By inhibiting the activity of these receptors, it blocks the growth and proliferation signal transduction of tumor cells, thus inhibiting tumor growth[22].