3.1 Expression of STARD7 in tumor and non-tumor tissue samples

To explore the expression of STARD7 in tumor and non-tumor tissues, we analyzed 33 cancer RNAseq data from TCGA using R software (Fig. 1A). The results showed that STARD7 was differentially expressed in 25 tumors and was highly expressed in 22 tumors. In addition, we analyzed the expression of STARD7 in 23 paired tumors in TCGA. We found that STARD7 is highly expressed in BLCA, BRCA, CHOL, COAD, ESCA, HNSC, LIHC, PRAD, STAD, and opposite expression in KICH, KIRC, LUAD, and THCA (Fig. 1B).

Fig. 1

Expression of STARD7. A Comparison of STARD7 between tumor and non-tumor tissues. B Comparison of STARD7 between paired tumor and non-tumor tissue. C Comparison of STARD7 protein between tumor and non-tumor tissues. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001

Additionally, proteomic data were utilized to assess the expression levels of the STARD7 protein in tumors. Figure 1C indicates that STARD7 is significantly overexpressed in COAD and LIHC, while it is under expressed in KIRP, LUAD, and UCEC. In addition, to evaluate the predictive value of STARD7 in tumors, ROC curves were used to analyze the differential value of STARD7 expression data in tumor tissue and non-tumor tissue (Figure S1). The results indicated that STARD7 exhibited strong discriminative value (AUC > 0.900) in CHOL, COAD, PAAD, READ, TGCT and UCS.

3.2 The prognostic value of STARD7 in tumors

Subsequently, we explored the correlation between STARD7 and OS in cancer patients through the Kaplan–Meier Plotter database. Cox proportional risk model analysis indicated that STARD7 functions as a high-risk gene in LAML, LIHC, UVM, LGG, while serving as a protective gene in KIRC and KIPA (Figure S2). Kaplan–Meier curve analysis suggests that high expression of STARD7 is associated with poorer survival in LIHC, THCA, THYM, and UCEC (Fig. 2F, J, K, L). In contrast, high STARD7 expression correlates with better survival in LUSC, BLCA, CESC, ESCA, KIRC, KIRP, LUAD and PAAD (Fig. 2A–I).

Fig. 2

The Kaplan-Meier curve of STARD7 is at A BLCA, B CESC, C ESCA, D KIRC, E KIRP, F LIHC, G LUAD, H LUSC, I PAAD, J THCA, K THYM, L UCEC

Furthermore, we analyzed the correlation between STARD7 and OS in tumor patients utilizing the TCGA database. The results analysis results for KIRC, LIHC and LUAD were consistent with those finds from Kaplan–Meier Plotter database (Figure S3).

3.3 STARD7 exhibits a wide range of mutations in tumors

Gene mutations play an important role in the occurrence and development of tumors. We analyzed the mutation of STARD7 in tumors and found that STARD7 is mutated in 20 tumors, primarily in the form of mutations and amplifications. Among them, UCEC, BLCA, and NSCLC were identified as tumors with high mutation rate (Fig. 3A). The most common mutation site of STARD7 is R232W (Fig. 3B, , C), and STARD7 mutation is associated with poorer OS, DSF, DF, and PF in LIHC patients (Fig. 3D).

Fig. 3

STARD7 mutations in tumors. A Frequency and type of mutations in the STARD7 gene change in pan-cancer. B, C STARD7 mutation in protein structure. D Kaplan-Meier curve of the STARD7 mutation at LIHC

3.4 Correlation between STARD7 expression and clinical phenotype

We analyzed the correlation between STARD7 expression and clinical phenotype. According to age, patients were divided into < 60 and ≥ 60 groups. The results showed that STARD7 was positively correlated with patients’ age in LGG and STAD, and negatively correlated with patients’ age in KIRP, LUSC, and OV (Figure S4).

Furthermore, we explored the relevance of STARD7 expression in classifying tumors. The results showed that high expression of STARD7 was positively correlated with tumor grade in HNSC, UCEC, and negatively correlated with tumor grade in KIRC (Fig. 4A–C) High expression of STARD7 was positively correlated with tumor stage and T phase at LIHC (Fig. 4E, H). There was a negative correlation with tumor Stage in KIRC, THCA (Fig. 4D, F, G, I).

Fig. 4

Correlation between STARD7 expression and tumor type. A–I HNSC, KIRC, UCEC, KIRC, LIHC, THCA, KIRC, LIHC, THCA

3.5 Correlation between STARD7 expression and immunity

The tumor immune microenvironment plays a key role in promoting tumor occurrence, development, metastasis, recurrence, drug resistance and immunosuppression through complex intercellular signaling. Therefore, we further investigated the relationship between STARD7 and the tumor immune microenvironment. We employed the ESTIMATE algorithm to calculate ImmuneScore, StromalScore, and ESTIMATEScore for STARD7 in 33 cancer types. Our analysis revealed that STARD7 was negatively correlated with ImmuneScore in eight tumors (Fig. 5A). STARD7 is negatively related to the StromalScore in GBM (r = 0.35, p = 9.3 e−6), WT (r = 0.42, p = 1.3 e−4), THCA e−13 (r = 0.32, p = 1.9) and NB (r = 0.49, p = 8.3e−11), TGCT (r = − 0.33, p = 1.0e−4), and LAML (r = 0.45, p = 2.7e−12) were positively correlated with StromalScore (Fig. 5B). In addition, STARD7 was negatively correlated with ESTIMATEScore in six tumors (Fig. 5C).

Fig. 5

Association between STARD7 expression and immune score. A–C Correlation between STARD7 and ImmuneScore, StromalScore, and ESTIMATEScore

To further explore the relationship between STARD7 and the immune microenvironment, we analyzed the correlation between STARD7 and immune cells and immune checkpoint genes in tumors. The results indicate that STARD7 exhibits a positive correlation with resting memory CD4 T cells, M1 macrophages, and M2 macrophages in most tumors. Conversely, it shows a negative correlation with memory B cells, plasma cells, and regulatory T cells (Tregs) in most tumors. (Figure S5A). in addition, we also found that STARD7 was positively correlated with immune checkpoint genes (CD274, CTLA4, HAVCR2, LAG3, PDCD1, PDCD1LG2, TIGIT, SIGLEC15) in PAAD, STAD, and UVM (Figure S5B).

The TISIDB website was utilized for analysis, which focused on six immune subtypes, including C1 (wound healing), C2 (IFN-gamma dominant), C3 (inflammatory), C4 (lymphocyte depleted), C5 (immunologically quiet) and C6 (TGF-b dominant). We found that STARD7 expression differed significantly in at least one of the six immune subtypes in 17 tumors (Figure S6). Among BLCA, BRCA, COAD, LUAD, MESO, SARC, the expression of STARD7 is relatively high in C2; Among COAD, LUSC, OV, STAD, UCEC, the expression of STARD7 is relatively low in C3; However, among KIRC and KIRP, STARD7 expression is relatively high in C5.

3.6 Correlation between STARD7 expression and TMB and MSI in tumors

Then, we explored the correlation of STARD7 expression levels with TMB and tumor MSI. The results showed that the expression level of STARD7 was significantly correlated with TMB in 12 tumors (Fig. 6A). STARD7 exhibits a positive correlation with tumor mutational burden (TMB) in bladder cancer (BLCA), breast cancer (BRCA), and glioblastoma (GBM), among others, while showing a negative correlation with TMB in thyroid carcinoma (THCA), uterine corpus endometrial carcinoma (UCEC), and uveal melanoma (UVM). Additionally, STARD7 expression levels demonstrate a significant correlation with microsatellite instability (MSI) in eight tumors (Fig. 6B). Specifically, STARD7 is positively correlated with MSI in cervical squamous cell carcinoma (CESC), cholangiocarcinoma (CHOL), esophageal carcinoma (ESCA), and stomach adenocarcinoma (STAD), while a negative correlation is observed in diffuse large B-cell lymphoma (DLBC), lower-grade glioma (LGG), prostate adenocarcinoma (PRAD), and THCA.

Fig. 6

STARD7 expresses the association with TMB and MSI. A. Correlation between STARD7 and TMB. B. Correlation between STARD7 and MSI

3.7 Correlation between STARD7 expression and DNA methylation in tumors

We next explored STARD7 methylation levels in tumors via the Disease Meth database. Significant differences in STARD7 methylation levels were observed across 20 tumor types (Fig. 7A–T). STARD7 methylation levels increased significantly in CHOL, KIRC, LUSC, SARC, and decreased in ACC, BLCA, CESC, COAD, HNSC, KICH, LAML, LGG, LIHC, OV, PAAD, PRAD, READ, TGCT, UCEC, UCS.

Fig. 7

STARD7 methylation levels in tumors

In addition, we analyzed the prognostic value of STARD7 methylation levels in the tumor via the KM curve. STARD7 hypermethylation is associated with poorer overall survival (OS) in CESC and improved OS in CHOL and COAD (Fig. 8A). Additionally, STARD7 hypermethylation correlates with poor progression-free interval (PFI) in BLCA, CESC, and LGG, while it is associated with better PFI in CHOL and OV (Fig. 8B). Furthermore, STARD7 hypermethylation is linked to improved DFI in OV (Fig. 8C).

Fig. 8

Prognostic value of STARD7 methylation levels

3.8 Relative expression of STARD7 in HCC cell lines

STARD7 expression in HCC cell lines was examined by qRT-PCR. As shown in Fig. 9A, STARD7 expression was significantly upregulated in HCC cells (HepG-2 and SMMC-7721) compared to human normal hepatocytes (THLE-2), particularly in SMMC-7721 cells, where the STARD7 expression level was more than twice that of HepG-2 cells.

Fig. 9

Downregulation of STARD7 suppresses HCC cells vitality. A. Expression of STARD7 in HCC cell lines measured by qRT-PCR. B, C Expression of STARD7 detected after si‑STARD7 transfection in HepG-2 and SMMC-7721 cells by qRT-PCR. D, E CCK-8 assay used to detect cell viability of HepG-2 and SMMC-7721 cells after STARD7 knockdown. *P < 0.05, **P < 0.01

3.9 Effect of STARD7 on proliferation of HCC cells

To investigate the impact of STARD7 on cellular proliferation in hepatocellular carcinoma (HCC), we transfected siRNAs specific to STARD7 (si-STARD7) into both HepG-2 and SMMC-7721 cell lines. Figure 9B, C illustrate the efficacy of si-STARD7 in downregulating the expression of STARD7 in these cell lines. Subsequently, we evaluated the proliferation of HepG-2 and SMMC-7721 cells using the CCK-8 assay. Our findings, as depicted in Fig. 9D, E revealed that the knockdown of STARD7 led to a significant inhibition of cellular proliferation in both cell lines compared to the negative control (si-NC).

3.10 Effect of STARD7 on invasion and migration of HCC cells

Cell migration and invasion abilities were assessed by transwell assay. As shown in Fig. 10A–D. Compared to the negative control (si‐NC), transfection with si‐STARD7 significantly inhibited the migration and invasion of HepG-2 and SMMC-7721 cells. Notably, the inhibitory effect of si‐STARD7 was more pronounced in SMMC-7721 cells than in HepG-2 cells.

Fig. 10

Downregulation of STARD7 suppresses HCC migration and invasion. A Migration and B invasion of HepG-2 cells following STARD7 knockdown. C Migration and D invasion of SMMC-7721 cells following STARD7 knockdown. *P < 0.05, **P < 0.01